丙泊酚对匹鲁卡品诱发大鼠癫痫持续状态的抑制作用及相关机制研究
|
摘要
第一部分:丙泊酚对匹鲁卡品诱发大鼠癫痫持续状态的治疗作用
目的建立可逆性胆碱酯酶抑制剂匹鲁卡品诱发大鼠癫痫持续状态(Status Epilepticus,SE)模型,观察不同剂量静脉麻醉药丙泊酚在癫痫发作后30 min给药对大鼠SE的影响。方法在大鼠上建立氯化锂(3mmol/kg)-匹鲁卡品(30mg/kg)诱发SE模型,以行为学、脑电图(electroencephalogram,EEG)上典型癫痫波的变化、动物24h存活数及皮层和海马的病理变化为观察指标,评价比较不同剂量(mg/kg)丙泊酚(12.5、25、50、75及100),安定(10)、东莨菪碱(10)及MK-801(2)对SE的抑制作用。结果1.氯化锂(3mmol/kg)-匹鲁卡品(30mg/kg)可诱发SE,给予匹鲁卡品后15min,动物开始出现行动迟缓、呆滞,面部抽搐、点头样运动、尾巴僵直并翘尾,20-25min后开始出现四肢强直性抽搐,最后发展成为以持续性全身性强直发作为特征的SE,在EEG上可观察到SE所特有的、持续的高幅高频惊厥波。2.行为学及EEG结果显示,丙泊酚(50～100)mg/kg对SE具确切治疗效果,并可显著降低SE动物死亡数(P＜0.05)。3.SE出现后30min i.p.东莨菪碱(10mg/kg)、MK-801(2mg/kg)及安定(10mg/kg),除东莨菪碱外,MK-801及安定对SE亦有较为明显抑制作用,其抗惊效果与丙泊酚中、高剂量组相当。4.HE染色结果显示,SE反复发作24h后皮层和海马CA1区细胞数明显减少,有的细胞肿胀破裂,轮廓模糊界限不清,排列紊乱,而海马其它各区变化不甚明显。丙泊酚组、DZP组和MK-801组细胞数较SE组明显增多(P＜0.05)。结论1.氯化锂(3mmol/kg)-匹鲁卡品(30mg/kg)可诱发典型的SE状态,SE发作后24h皮层和海马可见明显的细胞损伤。2.丙泊酚对氯化锂-匹鲁卡品诱发的SE具有确切的治疗效果,可明显改善EEG变化,增加出现SE动物24 h存活数,改善皮层和海马细胞的损伤程度,提示丙泊酚在SE治疗上具潜在应用价值。
第二部分:丙泊酚对致死剂量NMDA中毒小鼠的保护作用
目的:建立N-甲基-D-天冬氨酸(N-methyl-D-aspartate,NMDA)致死模型,观察丙泊酚对致死剂量NMDA中毒小鼠的保护作用。方法:给予致死剂量NMDA前10min,腹腔注射不同剂量(mg/kg)丙泊酚12.5、25、50、75及100,NMDA受体拮抗剂MK-801(2 mg/kg)及等容积脂肪乳(丙泊酚溶剂),以中毒动物存活率为评价指标,观察上述药物对致死剂量NMDA中毒小鼠的保护作用。结果:腹腔注射NMDA 175mg/kg可导致小鼠全身惊厥发作及快速死亡;丙泊酚(12.5,25,50,75及100mg/kg)可剂量依赖性抑制NMDA致死效应,显著降低中毒小鼠死亡率;其作用类似于NMDA受体拮抗剂MK801(存活率100%);而脂肪乳对致死剂量NMDA中毒小鼠无保护作用。结论:丙泊酚(12.5～100)mg/kg可剂量依赖性的对抗NMDA诱发的致死效应;丙泊酚可能存在对NMDA受体的直接或间接拮抗作用。
第三部分:丙泊酚对匹鲁卡品诱发SE大鼠皮层和海马NMDA受体亚型表达的影响
目的在大鼠上建立可逆性胆碱酯酶抑制剂匹鲁卡品诱发SE模型,观察丙泊酚对SE大鼠皮层和海马NMDA受体亚型(2A,2B)表达的影响。方法60只SD大鼠随机分为6组,分别为空白对照组(BLK组)、SE组(SE组)、丙泊酚50mg/kg组(PPF组)、安定10mg/kg组(DZP组)、东莨菪碱10mg/kg组(SCOP组)及MK-801(2mg/kg)组(MK-801组)。除BLK组外,其他各组大鼠均给予氯化锂(3mmol/kg)及匹鲁卡品(30mg/kg),建立匹鲁卡品诱发SE模型。待SE出现后30min,各治疗组动物分别腹腔注射丙泊酚等治疗药物及等容量生理盐水(BLK组和SE组)。24h后,将存活动物分两批处理,每组取3只大鼠进行心脏灌注后取大脑行免疫组化分析;剩余大鼠(每组取4只)断头取脑,快速剥离皮层和海马进行蛋白免疫印迹(Western Blot)分析。采用免疫组化和Western Blot法观察丙泊酚对SE大鼠发作24h后皮层和海马NMDA受体2A、2B亚型表达的影响。结果1.SE反复发作后24h,与BLK组相比,SE组大鼠皮层和海马NMDA受体2A、2B亚型阳性细胞数显著增加(P＜0.05);2.与SE组相比,丙泊酚50mg/kg给药组动物皮层和海马NMDA受体(2B)亚型表达显著降低(P＜0.05)。免疫组化结果发现,在海马区NR2B亚型表达显著降低,阳性细胞数显著减少(P＜0.05);而NMDA受体2A亚型在各区表达均无明显变化。3.MK-801(2mg/kg)可显著降低皮层和海马NMDA受体2A、2B亚型的表达,与SE组相比有显著统计学差异(P＜0.05),但安定(10mg/kg)和东莨菪碱(10mg/kg)对NMDA受体2A和2B亚型无明显影响。结论1.SE出现后24h,皮层和海马NMDA受体(2A和2B)亚型表达显著上调。2.丙泊酚可显著抑制皮层和海马NMDA受体2B亚型表达,但对NMDA受体2A亚型表达无明显影响,其作用与特异性NMDA受体拮抗剂MK-801类似,但与GABA受体激动剂安定及抗胆碱药东莨菪碱存在显著差别;3.丙泊酚对拟胆碱药匹鲁卡品诱发SE的抑制作用可能与其下调NMDA受体2B亚型的表达有关。
第四部分:丙泊酚对匹鲁卡品诱发SE大鼠大脑皮层和海马GABA_A受体α_1亚型表达的影响
目的建立可逆性胆碱酯酶抑制剂匹鲁卡品诱发大鼠SE模型,观察丙泊酚对匹鲁卡品诱发SE大鼠皮层和海马GABAA受体α_1亚型表达的影响。方法50只SD大鼠随机分为5组,包括空白对照组(BLK组)、SE组(SE组)、东莨菪碱10mg/kg组(SCOP组)、丙泊酚50mg/kg组(PPF组)及安定10mg/kg组(DZP组)。除BLK组外,其他各组动物均腹腔注射氯化锂(3mmol/kg)-匹鲁卡品(30mg/kg),建立匹鲁卡品诱发SE模型。待SE出现后30min,分别给予丙泊酚50mg/kg、东莨菪碱10mg/kg及安定10mg/kg等不同治疗药物,空白对照组和模型组给予等量的生理盐水。24h后,取3只大鼠进行心脏灌注后取皮层和海马行免疫组化分析;剩余大鼠行蛋白免疫印迹分析(WesternBlot)。采用免疫组化和Western Blot法观察丙泊酚对SE大鼠发作24h后皮层和海马GABA_A受体α_1亚型表达的影响。结果1.SE出现后24h,皮层和海马GABA_A受体α_1亚型表达均显著降低,与BLK组相比有显著差异(P＜0.05);2.丙泊酚50mg/kg可显著上调皮层和海马GABA_A受体α_1亚型表达,与SE组相比有显著差异(P＜0.05);其作用类似于GABA受体激动剂安定(10mg/kg),而东莨菪碱(10mg/kg)对GABA_A受体α_1亚型无明显影响。结论1.SE出现后24h,GABA_A受体α_1亚型表达下调。2.丙泊酚可显著上调GABA_A受体α_1亚型表达。
第五部分:丙泊酚治疗癫痫持续状态的抗氧化机理研究
目的在大鼠上建立可逆性胆碱酯酶抑制剂匹鲁卡品诱发SE模型,观察丙泊酚对SE大鼠血清、皮层和海马超氧化物歧化酶(SOD)、谷胱甘肽(GSH)和丙二醛(MDA)水平的影响。方法72只SD大鼠随机分为6组,包括空白对照组(BLK组)、SE组(SE组)、丙泊酚50mg/kg组(PPF组)、安定10mg/kg组(DZP组)、东莨菪碱10mg/kg组(SCOP组)及MK-801(2mg/kg)组(MK-801组)。待SE出现后30min,分别给予不同药物及等容积生理盐水。采用分光光度法测定给药后2h及24h动物血清、海马及皮层内SOD、GSH及MDA值。结果1.SE发作后30min给予各实验用药(BLK组和SE组给予等容量的生理盐水),给药后2h,SE组血清、皮层及海马内SOD及MDA水平显著升高,GSH含量显著降低,与BLK组相比有显著差异(P＜0.01);2.与SE动物相比,丙泊酚给药组动物SOD无明显改变,但GSH可显著升高而MDA含量显著降低(P＜0.01);但安定、东莨菪碱及MK-801给药组动物与SE组动物相比无显著改变。3.给药后24h,血清、皮层及海马内SOD、MDA及GSH水平与给药后2h存在类似变化,与BLK组相比具显著统计学意义(P＜0.01);4.给药后24h,与模型组动物相比,丙泊酚给药组动物血清及皮层、海马内GSH显著增高,MDA显著降低(P＜0.01),但SOD含量未见显著改变;安定、东莨菪碱和MK-801给药组动物血清及皮层、海马内SOD、GSH及MDA含量与模型组相比未见显著改变。结论1.SE出现后2及24h,SE大鼠血清、皮层和海马SOD活性显著增加、GSH显著降低、MDA显著升高。2.在给药后2h及24h,丙泊酚50mg/kg均可显著升高SE大鼠血清、大脑皮层和海马GSH水平,降低MDA含量,提示丙泊酚对提升SE动物抗氧化应激水平有一定促进作用。
Part 1 Inhibition of Propofol on Lithium-Pilocarpine Induced Status Epilepticus in rats
Objective To observe the inhibition of propofol in different dose on status epilepticus(SE) induced by pilocarpine,and explore the therapeutic effect of propofol in SE 30min after admistration.Methods 80 SD rats were divided into 10 groups randomly,include blank(BLK),SE,propofol at dose of 12.5,25,50,75 and 100 mg/kg,diazepam(DZP,mg/kg),scoplamine(SCOP,10 mg/kg) and MK801(2 mg/kg) group respectively.Following establishing SE model in rats induced by pilocarpine,every agent was injected i.p.after 30min when the SE is occurred(equal volume normal saline was injected in the blank group),the EEG was recorded continuously for 5 hours and the survival rates of SE rats after 24 hours.At the same time,efficacy of the diazepam,scopolamine and MK801 on SE were also observed.And evaluating the pathologic changes in rats cortex and hippocampus with HE stain.Observing the effects of propofol on cortical and hippocampal pathologic changes in rats.Results 1.15min after injection of pilocarpine produced a sequence ofbehavioural alterations such as initial akinesia, tremor of the whole body and/or incomplete limbic gustatory automatisms. Gustatory automatism is considered to be a type of preconvulsive behaviour, characterized by myoclonic twitching which is restricted to the head and face and is accompanied with salivation.Those changes were followed by episodes of motor limbic seizures,with or without loss of the righting reflex and persistent general tonic seizure.The EEG showed that the waves from baseline wave to high-frequency,high-amplitude spikes wave continuously in cortex and hippocampus about 10-20 minutes after the injection of pilocarpine.2. Behavioral and EEG analysis revealed that propofol significantly reversing the seizure,decreasing the mortality of the SE rats in 24 hours,meanwhile,diazepam and MK-801 showed the same effects.But the scopolamine 10mg/kg i.p.seizure onset after 30min is hardly effective on SE.The EEG records showed that propofol at dose of 50,75 and 100 mg/kg can effectively decrease the high-frequency,high-amplitude spikes induced by SE.Propofol at 12.5 and 25mg/kg is nearly ineffective on the SE,the amplitudes and frequency of EEG were hardly improved during this time.Although sharp waves were still showed occasionally at 50,75 and 100mg/kg,the epileptic seizure of ethology was not happened.Meanwhile,the EEG records showed that Mk801 and diazepam were effective on the SE induced by pilocarpine,whereas the anticholinergic drug scopolamine was ineffective on EEG after 30 minutes when the SE was occurred. 3.The HE stain showed that cells were decreased significantly in cortex and hippocampus CA1 region when SE onset after 24h,and cellular swelling, plasmatorrhexis,dislimn were observed.However,Compared with SE group,the cells were increased in propofol,diazepam and MK801 group obviously. Conclusions 1.Lithium-pilocarpine can induced typical SE in rats,seizure onset after 30min,the developmental mechanism of SE maybe have no connection with the central cholinergic system.2.Our results show that propofol can effectively inhibit the SE induced by lithium-pilocarpine,improving the EEG changes of SE rats,increasing the SE rats' survival rates,and improving the impared degree of cortical and hippocampal cell.These results also implied that propofol maybe as potential agent for treatment of SE in clinical.
Part 2 Protection of Propofol on Toxic Mouse Induced by Lethal dose of N-methyl-D-aspartate
Objective:To observe propofol's protective effect on ethology and survival rates of mice treated by N-methyl-D-aspartate(NMDA) at lethal dose,and to investigate the anticonvulsive mechanism of propofol.Methods:Following establishing lethal model in mice induced by NMDA at dose of 175 mg/kg, propofol at dose of 12.5,25,50,75 and 100 mg/kg was injected intraperitoneally (i.p.) just before administration of NMDA in different groups of mice.The positive control drug was the nonspecific NMDA receptor antagonist MK801(2mg/kg i.p.).The ethological changes and survival rates of mice were recorded in these groups.Results:NMDA at dose of 175 mg/kg resulted in general seizure,and made all mice die 10 min after convulsion.When propofol at dose of 12.5,25,50,75 and 100 mg/kg was administrated intraperitoneally to mice 10 min before NMDA injection,the rates of convulsion were decreased and the survival rates were increased at the dose dependent manner.Conclusions:1. NMDA 175mg/kg can result in generalized convulsion,and causing all the mice died.2.Propofol can dose-dependent protect mice against the toxicity of NMDA at lethal dose.These results suggesting that anticonvulsive effect of propofol maybe result from its action on the NMDA receptors.
Part 3 The study of NMDA receptors mechanism during Inhibition of Propofol on Lithium-Pilocarpine Induced Status Epilepticus in rats
Objective Establishing status epilepticus(SE) model in rats induced by Lithium- pilocarpine(Li-pilo),to observe the effects of propofol on N-methyl-D-aspartate receptor subunit 2A(NR2A) and 2B(NR2B) in SE rats cortical and hippocampal expression.Methods 60 SD rats were divided into 6 groups randomly,include blank,SE,propofol(50mg/kg),diazepam(10mg/kg), scoplamine(10mg/kg) and MK801(2mg/kg) group respectively.Following establishing SE model in rats induced by Li-pilo except blank group.Convulsion intensity was quantified according to the Racine rating scale.Only the rats received pilocaroine were observed stage 4 and 5 behaviors onset and recurrent attacks can be put into the experiments.Every agent was injected intraperitoneally 30min after the SE is occurred,equal volume normal saline was injected in the blank group.The rats were sacrificed 24h following pilocarpine administration. Immunohistochemistry and Western Blot were employed to determine the cortical and hippocampal expression of NR2A and NR2B in SE rats.Results Immunohistochemistry and Western Blot analysis showed that the expression level of NR2A and NR2B subunits were significantly upregulated in cortices and hippocampus when SE occurred after 24 hours,compared with blank group, P＜0.05.However,propofol at dose of 50mg/kg,which is anesthetic dose,can decrease the NR2B subunit expression significantly,compared with SE group, P＜0.05,whereas the NR2A subunit expression was nearly unchanged.MK801 at dose 2mg/kg can antagonize the NR2A and NR2B subunits expression,compared with SE group,P＜0.05.But the diazepam and scopolamine were not modified the expression level of NR2A and NR2B subunits.Conclusions Our results show that the inhibitive mechanism of propofol on SE rats induced by Li-pilo maybe, at least in part,contribute to its effect of downregulating the expression level of NR2B subunit.These results imply that propofol maybe as a potential agent for treatment of status epilepticus in clinical.
Part 4 The study of GABA_A receptors mechanism of propofol on Lithium-Pilocarpine Induced Status Epilepticus in rats
Objective Establishing status epilepticus(SE) model in rats induced by Lithiumpilocarpine (Li-pilo),to observe the effects of propofol on cortical and hippocampal GABA_A receptorα_1 subunit expression in SE rats induced by Li-pilo.Methods 50 SD rats were divided into 5 groups randomly,include blank,SE,propofol(50mg/kg),diazepam(10mg/kg) and scoplamine(10mg/kg) group respectively.Following establishing SE model in rats induced by Li-pilo except blank group.Convulsion intensity was quantified according to the Racine rating scale.Only the rats received pilocaroine were observed stage 4 and 5 behaviors onset and recurrent attacks can be put into the experiments.Every agent was injected intraperitoneally 30min after the SE is occurred,equal volume normal saline was injected in the blank group.The rats were sacrificed 24h following pilocarpine administration.Immunohistochemistry and Western Blot were employed to determine the cortical and hippocampal expression of NR2A and NR2B in SE rats.Results Immunohistochemistry and Western Blot analysis showed that the expression of GABAA receptorα_1 subunit were significantly decreased in cortices and hippocampus when SE occurred after 24 hours. Expression level of GABA_A receptorα_1 subunit were significantly downregulated in cortices and hippocampus when SE occurred after 24 hours,compared with blank group,P＜0.05.Propofol at dose of 50mg/kg,which is anesthetic dose,can significantly upregulate the GABAA receptorα_1 subunit expression in cortices and hippocampus,compared with SE group,P＜0.05.The diazepam at dose of 10mg/kg can also increase the GABA_A receptorα_1 subunit expression.But scopolamine were not modified the expression level of GABA_A receptorα_1 subunit expression.Conclusions Our results show that the inhibitive mechanism of propofol on SE rats induced by Li-pilo maybecontribute to its upregulate the expression level of GABA_A receptorα_1 subunit.These results also imply that propofol maybe as a good agent for treatment of status epilepticus in clinical.
Part 5 Study of antioxidant effects of propofol on Lithium-Pilocarpine Induced Status Epilepticus in rats
Objective Establishing status epilepticus(SE) model in rats induced by Lithiumpilocarpine (Li-pilo),to observe the effects of propofol on serum,cortical and hippocampal superoxide dismutase(SOD),glutathione(GSH) and malondialdehyde(MDA) in SE rats induced by Li-pilo.Methods 72 SD rats were divided into 6 groups randomly,include blank,SE,propofol(50mg/kg), diazepam(10mg/kg),scoplamine(10mg/kg) and MK801(2mg/kg) group respectively.Following establishing SE model in rats induced by Li-pilo except blank group.Convulsion intensity was quantified according to the Racine rating scale.Only the rats received pilocaroine were observed stage 4 and 5 behaviors onset and recurrent attacks can be put into the experiments.Every agent was injected intraperitoneally 30min after the SE is occurred,equal volume normal saline was injected in the blank group.2 hours after the agents were given,4 rats of every group were exsanguinated from fossa orbitalis,and centrifugated(1500rpm,15min),drown the supernatant into Epidoff tube to measure the protein level and optical density(OD).Then the 4 rats were sacrificed and the frontal cortex and hippocampus were rapidly and carefully removed. Frontal cortex and hippocampi of the same group were put into a Epidoff tube, and weighted,homogenized at 4℃in distilled water,centrifugated and(12000 rpm,20 min at 4℃),drown the supernatant into different Epidoff tube to measure the protein level and OD.After 24 hours when the agents were given,the same procedure were taken as the time of 2 hours when the agents were given.The OD of SOD,GSH and MDA were measured according to the procedure of kits description Results After 2 hours when the agents were given,SOD activity and MDA in serum,frontal cortex and hippocampus were increased significantly, GSH in these areas were decreased remarkably,compared with the blank group, P＜0.01.The GSH was increased and MDA was decreased notably in propofol group after 2 hours when the agents were given,compared with SE group,P＜0.01. But propofol was not changed the SOD activity augmentation in SE rats. Diazepam,scoplamine and MK801 were not affected on SOD,GSH and MDA both serum and cortex and hippocampus.After 24 hours when the agents were given,SOD activity and MDA in serum,frontal cortex and hippocampus were increased significantly also,GSH in these areas were decreased remarkably, compared with the blank group,P＜0.01.propofol was not changed the SOD activity augmentation in SE rats either.Diazepam,scoplamine and MK801 were not affected on SOD,GSH and MDA in these areas.
Conclusions 1.SOD activity in serum,frontal cortex and hippocampus were increased significantly after 2 hours and 24 hours in SE rats,the MDA was increased also,whereas the GSH was decreased remarkable.2.Propofol can increase GSH and decrease MDA level depression either serum or cortex and hippocampus in SE rats.Our results imply that the inhibition of propofol on Li-pilo induced SE in rats is contribute to its antioxidant properties though down-regulating the MDA and up-regulating GSH level.
目的建立可逆性胆碱酯酶抑制剂匹鲁卡品诱发大鼠癫痫持续状态(Status Epilepticus,SE)模型,观察不同剂量静脉麻醉药丙泊酚在癫痫发作后30 min给药对大鼠SE的影响。方法在大鼠上建立氯化锂(3mmol/kg)-匹鲁卡品(30mg/kg)诱发SE模型,以行为学、脑电图(electroencephalogram,EEG)上典型癫痫波的变化、动物24h存活数及皮层和海马的病理变化为观察指标,评价比较不同剂量(mg/kg)丙泊酚(12.5、25、50、75及100),安定(10)、东莨菪碱(10)及MK-801(2)对SE的抑制作用。结果1.氯化锂(3mmol/kg)-匹鲁卡品(30mg/kg)可诱发SE,给予匹鲁卡品后15min,动物开始出现行动迟缓、呆滞,面部抽搐、点头样运动、尾巴僵直并翘尾,20-25min后开始出现四肢强直性抽搐,最后发展成为以持续性全身性强直发作为特征的SE,在EEG上可观察到SE所特有的、持续的高幅高频惊厥波。2.行为学及EEG结果显示,丙泊酚(50～100)mg/kg对SE具确切治疗效果,并可显著降低SE动物死亡数(P＜0.05)。3.SE出现后30min i.p.东莨菪碱(10mg/kg)、MK-801(2mg/kg)及安定(10mg/kg),除东莨菪碱外,MK-801及安定对SE亦有较为明显抑制作用,其抗惊效果与丙泊酚中、高剂量组相当。4.HE染色结果显示,SE反复发作24h后皮层和海马CA1区细胞数明显减少,有的细胞肿胀破裂,轮廓模糊界限不清,排列紊乱,而海马其它各区变化不甚明显。丙泊酚组、DZP组和MK-801组细胞数较SE组明显增多(P＜0.05)。结论1.氯化锂(3mmol/kg)-匹鲁卡品(30mg/kg)可诱发典型的SE状态,SE发作后24h皮层和海马可见明显的细胞损伤。2.丙泊酚对氯化锂-匹鲁卡品诱发的SE具有确切的治疗效果,可明显改善EEG变化,增加出现SE动物24 h存活数,改善皮层和海马细胞的损伤程度,提示丙泊酚在SE治疗上具潜在应用价值。
第二部分:丙泊酚对致死剂量NMDA中毒小鼠的保护作用
目的:建立N-甲基-D-天冬氨酸(N-methyl-D-aspartate,NMDA)致死模型,观察丙泊酚对致死剂量NMDA中毒小鼠的保护作用。方法:给予致死剂量NMDA前10min,腹腔注射不同剂量(mg/kg)丙泊酚12.5、25、50、75及100,NMDA受体拮抗剂MK-801(2 mg/kg)及等容积脂肪乳(丙泊酚溶剂),以中毒动物存活率为评价指标,观察上述药物对致死剂量NMDA中毒小鼠的保护作用。结果:腹腔注射NMDA 175mg/kg可导致小鼠全身惊厥发作及快速死亡;丙泊酚(12.5,25,50,75及100mg/kg)可剂量依赖性抑制NMDA致死效应,显著降低中毒小鼠死亡率;其作用类似于NMDA受体拮抗剂MK801(存活率100%);而脂肪乳对致死剂量NMDA中毒小鼠无保护作用。结论:丙泊酚(12.5～100)mg/kg可剂量依赖性的对抗NMDA诱发的致死效应;丙泊酚可能存在对NMDA受体的直接或间接拮抗作用。
第三部分:丙泊酚对匹鲁卡品诱发SE大鼠皮层和海马NMDA受体亚型表达的影响
目的在大鼠上建立可逆性胆碱酯酶抑制剂匹鲁卡品诱发SE模型,观察丙泊酚对SE大鼠皮层和海马NMDA受体亚型(2A,2B)表达的影响。方法60只SD大鼠随机分为6组,分别为空白对照组(BLK组)、SE组(SE组)、丙泊酚50mg/kg组(PPF组)、安定10mg/kg组(DZP组)、东莨菪碱10mg/kg组(SCOP组)及MK-801(2mg/kg)组(MK-801组)。除BLK组外,其他各组大鼠均给予氯化锂(3mmol/kg)及匹鲁卡品(30mg/kg),建立匹鲁卡品诱发SE模型。待SE出现后30min,各治疗组动物分别腹腔注射丙泊酚等治疗药物及等容量生理盐水(BLK组和SE组)。24h后,将存活动物分两批处理,每组取3只大鼠进行心脏灌注后取大脑行免疫组化分析;剩余大鼠(每组取4只)断头取脑,快速剥离皮层和海马进行蛋白免疫印迹(Western Blot)分析。采用免疫组化和Western Blot法观察丙泊酚对SE大鼠发作24h后皮层和海马NMDA受体2A、2B亚型表达的影响。结果1.SE反复发作后24h,与BLK组相比,SE组大鼠皮层和海马NMDA受体2A、2B亚型阳性细胞数显著增加(P＜0.05);2.与SE组相比,丙泊酚50mg/kg给药组动物皮层和海马NMDA受体(2B)亚型表达显著降低(P＜0.05)。免疫组化结果发现,在海马区NR2B亚型表达显著降低,阳性细胞数显著减少(P＜0.05);而NMDA受体2A亚型在各区表达均无明显变化。3.MK-801(2mg/kg)可显著降低皮层和海马NMDA受体2A、2B亚型的表达,与SE组相比有显著统计学差异(P＜0.05),但安定(10mg/kg)和东莨菪碱(10mg/kg)对NMDA受体2A和2B亚型无明显影响。结论1.SE出现后24h,皮层和海马NMDA受体(2A和2B)亚型表达显著上调。2.丙泊酚可显著抑制皮层和海马NMDA受体2B亚型表达,但对NMDA受体2A亚型表达无明显影响,其作用与特异性NMDA受体拮抗剂MK-801类似,但与GABA受体激动剂安定及抗胆碱药东莨菪碱存在显著差别;3.丙泊酚对拟胆碱药匹鲁卡品诱发SE的抑制作用可能与其下调NMDA受体2B亚型的表达有关。
第四部分:丙泊酚对匹鲁卡品诱发SE大鼠大脑皮层和海马GABA_A受体α_1亚型表达的影响
目的建立可逆性胆碱酯酶抑制剂匹鲁卡品诱发大鼠SE模型,观察丙泊酚对匹鲁卡品诱发SE大鼠皮层和海马GABAA受体α_1亚型表达的影响。方法50只SD大鼠随机分为5组,包括空白对照组(BLK组)、SE组(SE组)、东莨菪碱10mg/kg组(SCOP组)、丙泊酚50mg/kg组(PPF组)及安定10mg/kg组(DZP组)。除BLK组外,其他各组动物均腹腔注射氯化锂(3mmol/kg)-匹鲁卡品(30mg/kg),建立匹鲁卡品诱发SE模型。待SE出现后30min,分别给予丙泊酚50mg/kg、东莨菪碱10mg/kg及安定10mg/kg等不同治疗药物,空白对照组和模型组给予等量的生理盐水。24h后,取3只大鼠进行心脏灌注后取皮层和海马行免疫组化分析;剩余大鼠行蛋白免疫印迹分析(WesternBlot)。采用免疫组化和Western Blot法观察丙泊酚对SE大鼠发作24h后皮层和海马GABA_A受体α_1亚型表达的影响。结果1.SE出现后24h,皮层和海马GABA_A受体α_1亚型表达均显著降低,与BLK组相比有显著差异(P＜0.05);2.丙泊酚50mg/kg可显著上调皮层和海马GABA_A受体α_1亚型表达,与SE组相比有显著差异(P＜0.05);其作用类似于GABA受体激动剂安定(10mg/kg),而东莨菪碱(10mg/kg)对GABA_A受体α_1亚型无明显影响。结论1.SE出现后24h,GABA_A受体α_1亚型表达下调。2.丙泊酚可显著上调GABA_A受体α_1亚型表达。
第五部分:丙泊酚治疗癫痫持续状态的抗氧化机理研究
目的在大鼠上建立可逆性胆碱酯酶抑制剂匹鲁卡品诱发SE模型,观察丙泊酚对SE大鼠血清、皮层和海马超氧化物歧化酶(SOD)、谷胱甘肽(GSH)和丙二醛(MDA)水平的影响。方法72只SD大鼠随机分为6组,包括空白对照组(BLK组)、SE组(SE组)、丙泊酚50mg/kg组(PPF组)、安定10mg/kg组(DZP组)、东莨菪碱10mg/kg组(SCOP组)及MK-801(2mg/kg)组(MK-801组)。待SE出现后30min,分别给予不同药物及等容积生理盐水。采用分光光度法测定给药后2h及24h动物血清、海马及皮层内SOD、GSH及MDA值。结果1.SE发作后30min给予各实验用药(BLK组和SE组给予等容量的生理盐水),给药后2h,SE组血清、皮层及海马内SOD及MDA水平显著升高,GSH含量显著降低,与BLK组相比有显著差异(P＜0.01);2.与SE动物相比,丙泊酚给药组动物SOD无明显改变,但GSH可显著升高而MDA含量显著降低(P＜0.01);但安定、东莨菪碱及MK-801给药组动物与SE组动物相比无显著改变。3.给药后24h,血清、皮层及海马内SOD、MDA及GSH水平与给药后2h存在类似变化,与BLK组相比具显著统计学意义(P＜0.01);4.给药后24h,与模型组动物相比,丙泊酚给药组动物血清及皮层、海马内GSH显著增高,MDA显著降低(P＜0.01),但SOD含量未见显著改变;安定、东莨菪碱和MK-801给药组动物血清及皮层、海马内SOD、GSH及MDA含量与模型组相比未见显著改变。结论1.SE出现后2及24h,SE大鼠血清、皮层和海马SOD活性显著增加、GSH显著降低、MDA显著升高。2.在给药后2h及24h,丙泊酚50mg/kg均可显著升高SE大鼠血清、大脑皮层和海马GSH水平,降低MDA含量,提示丙泊酚对提升SE动物抗氧化应激水平有一定促进作用。
Part 1 Inhibition of Propofol on Lithium-Pilocarpine Induced Status Epilepticus in rats
Objective To observe the inhibition of propofol in different dose on status epilepticus(SE) induced by pilocarpine,and explore the therapeutic effect of propofol in SE 30min after admistration.Methods 80 SD rats were divided into 10 groups randomly,include blank(BLK),SE,propofol at dose of 12.5,25,50,75 and 100 mg/kg,diazepam(DZP,mg/kg),scoplamine(SCOP,10 mg/kg) and MK801(2 mg/kg) group respectively.Following establishing SE model in rats induced by pilocarpine,every agent was injected i.p.after 30min when the SE is occurred(equal volume normal saline was injected in the blank group),the EEG was recorded continuously for 5 hours and the survival rates of SE rats after 24 hours.At the same time,efficacy of the diazepam,scopolamine and MK801 on SE were also observed.And evaluating the pathologic changes in rats cortex and hippocampus with HE stain.Observing the effects of propofol on cortical and hippocampal pathologic changes in rats.Results 1.15min after injection of pilocarpine produced a sequence ofbehavioural alterations such as initial akinesia, tremor of the whole body and/or incomplete limbic gustatory automatisms. Gustatory automatism is considered to be a type of preconvulsive behaviour, characterized by myoclonic twitching which is restricted to the head and face and is accompanied with salivation.Those changes were followed by episodes of motor limbic seizures,with or without loss of the righting reflex and persistent general tonic seizure.The EEG showed that the waves from baseline wave to high-frequency,high-amplitude spikes wave continuously in cortex and hippocampus about 10-20 minutes after the injection of pilocarpine.2. Behavioral and EEG analysis revealed that propofol significantly reversing the seizure,decreasing the mortality of the SE rats in 24 hours,meanwhile,diazepam and MK-801 showed the same effects.But the scopolamine 10mg/kg i.p.seizure onset after 30min is hardly effective on SE.The EEG records showed that propofol at dose of 50,75 and 100 mg/kg can effectively decrease the high-frequency,high-amplitude spikes induced by SE.Propofol at 12.5 and 25mg/kg is nearly ineffective on the SE,the amplitudes and frequency of EEG were hardly improved during this time.Although sharp waves were still showed occasionally at 50,75 and 100mg/kg,the epileptic seizure of ethology was not happened.Meanwhile,the EEG records showed that Mk801 and diazepam were effective on the SE induced by pilocarpine,whereas the anticholinergic drug scopolamine was ineffective on EEG after 30 minutes when the SE was occurred. 3.The HE stain showed that cells were decreased significantly in cortex and hippocampus CA1 region when SE onset after 24h,and cellular swelling, plasmatorrhexis,dislimn were observed.However,Compared with SE group,the cells were increased in propofol,diazepam and MK801 group obviously. Conclusions 1.Lithium-pilocarpine can induced typical SE in rats,seizure onset after 30min,the developmental mechanism of SE maybe have no connection with the central cholinergic system.2.Our results show that propofol can effectively inhibit the SE induced by lithium-pilocarpine,improving the EEG changes of SE rats,increasing the SE rats' survival rates,and improving the impared degree of cortical and hippocampal cell.These results also implied that propofol maybe as potential agent for treatment of SE in clinical.
Part 2 Protection of Propofol on Toxic Mouse Induced by Lethal dose of N-methyl-D-aspartate
Objective:To observe propofol's protective effect on ethology and survival rates of mice treated by N-methyl-D-aspartate(NMDA) at lethal dose,and to investigate the anticonvulsive mechanism of propofol.Methods:Following establishing lethal model in mice induced by NMDA at dose of 175 mg/kg, propofol at dose of 12.5,25,50,75 and 100 mg/kg was injected intraperitoneally (i.p.) just before administration of NMDA in different groups of mice.The positive control drug was the nonspecific NMDA receptor antagonist MK801(2mg/kg i.p.).The ethological changes and survival rates of mice were recorded in these groups.Results:NMDA at dose of 175 mg/kg resulted in general seizure,and made all mice die 10 min after convulsion.When propofol at dose of 12.5,25,50,75 and 100 mg/kg was administrated intraperitoneally to mice 10 min before NMDA injection,the rates of convulsion were decreased and the survival rates were increased at the dose dependent manner.Conclusions:1. NMDA 175mg/kg can result in generalized convulsion,and causing all the mice died.2.Propofol can dose-dependent protect mice against the toxicity of NMDA at lethal dose.These results suggesting that anticonvulsive effect of propofol maybe result from its action on the NMDA receptors.
Part 3 The study of NMDA receptors mechanism during Inhibition of Propofol on Lithium-Pilocarpine Induced Status Epilepticus in rats
Objective Establishing status epilepticus(SE) model in rats induced by Lithium- pilocarpine(Li-pilo),to observe the effects of propofol on N-methyl-D-aspartate receptor subunit 2A(NR2A) and 2B(NR2B) in SE rats cortical and hippocampal expression.Methods 60 SD rats were divided into 6 groups randomly,include blank,SE,propofol(50mg/kg),diazepam(10mg/kg), scoplamine(10mg/kg) and MK801(2mg/kg) group respectively.Following establishing SE model in rats induced by Li-pilo except blank group.Convulsion intensity was quantified according to the Racine rating scale.Only the rats received pilocaroine were observed stage 4 and 5 behaviors onset and recurrent attacks can be put into the experiments.Every agent was injected intraperitoneally 30min after the SE is occurred,equal volume normal saline was injected in the blank group.The rats were sacrificed 24h following pilocarpine administration. Immunohistochemistry and Western Blot were employed to determine the cortical and hippocampal expression of NR2A and NR2B in SE rats.Results Immunohistochemistry and Western Blot analysis showed that the expression level of NR2A and NR2B subunits were significantly upregulated in cortices and hippocampus when SE occurred after 24 hours,compared with blank group, P＜0.05.However,propofol at dose of 50mg/kg,which is anesthetic dose,can decrease the NR2B subunit expression significantly,compared with SE group, P＜0.05,whereas the NR2A subunit expression was nearly unchanged.MK801 at dose 2mg/kg can antagonize the NR2A and NR2B subunits expression,compared with SE group,P＜0.05.But the diazepam and scopolamine were not modified the expression level of NR2A and NR2B subunits.Conclusions Our results show that the inhibitive mechanism of propofol on SE rats induced by Li-pilo maybe, at least in part,contribute to its effect of downregulating the expression level of NR2B subunit.These results imply that propofol maybe as a potential agent for treatment of status epilepticus in clinical.
Part 4 The study of GABA_A receptors mechanism of propofol on Lithium-Pilocarpine Induced Status Epilepticus in rats
Objective Establishing status epilepticus(SE) model in rats induced by Lithiumpilocarpine (Li-pilo),to observe the effects of propofol on cortical and hippocampal GABA_A receptorα_1 subunit expression in SE rats induced by Li-pilo.Methods 50 SD rats were divided into 5 groups randomly,include blank,SE,propofol(50mg/kg),diazepam(10mg/kg) and scoplamine(10mg/kg) group respectively.Following establishing SE model in rats induced by Li-pilo except blank group.Convulsion intensity was quantified according to the Racine rating scale.Only the rats received pilocaroine were observed stage 4 and 5 behaviors onset and recurrent attacks can be put into the experiments.Every agent was injected intraperitoneally 30min after the SE is occurred,equal volume normal saline was injected in the blank group.The rats were sacrificed 24h following pilocarpine administration.Immunohistochemistry and Western Blot were employed to determine the cortical and hippocampal expression of NR2A and NR2B in SE rats.Results Immunohistochemistry and Western Blot analysis showed that the expression of GABAA receptorα_1 subunit were significantly decreased in cortices and hippocampus when SE occurred after 24 hours. Expression level of GABA_A receptorα_1 subunit were significantly downregulated in cortices and hippocampus when SE occurred after 24 hours,compared with blank group,P＜0.05.Propofol at dose of 50mg/kg,which is anesthetic dose,can significantly upregulate the GABAA receptorα_1 subunit expression in cortices and hippocampus,compared with SE group,P＜0.05.The diazepam at dose of 10mg/kg can also increase the GABA_A receptorα_1 subunit expression.But scopolamine were not modified the expression level of GABA_A receptorα_1 subunit expression.Conclusions Our results show that the inhibitive mechanism of propofol on SE rats induced by Li-pilo maybecontribute to its upregulate the expression level of GABA_A receptorα_1 subunit.These results also imply that propofol maybe as a good agent for treatment of status epilepticus in clinical.
Part 5 Study of antioxidant effects of propofol on Lithium-Pilocarpine Induced Status Epilepticus in rats
Objective Establishing status epilepticus(SE) model in rats induced by Lithiumpilocarpine (Li-pilo),to observe the effects of propofol on serum,cortical and hippocampal superoxide dismutase(SOD),glutathione(GSH) and malondialdehyde(MDA) in SE rats induced by Li-pilo.Methods 72 SD rats were divided into 6 groups randomly,include blank,SE,propofol(50mg/kg), diazepam(10mg/kg),scoplamine(10mg/kg) and MK801(2mg/kg) group respectively.Following establishing SE model in rats induced by Li-pilo except blank group.Convulsion intensity was quantified according to the Racine rating scale.Only the rats received pilocaroine were observed stage 4 and 5 behaviors onset and recurrent attacks can be put into the experiments.Every agent was injected intraperitoneally 30min after the SE is occurred,equal volume normal saline was injected in the blank group.2 hours after the agents were given,4 rats of every group were exsanguinated from fossa orbitalis,and centrifugated(1500rpm,15min),drown the supernatant into Epidoff tube to measure the protein level and optical density(OD).Then the 4 rats were sacrificed and the frontal cortex and hippocampus were rapidly and carefully removed. Frontal cortex and hippocampi of the same group were put into a Epidoff tube, and weighted,homogenized at 4℃in distilled water,centrifugated and(12000 rpm,20 min at 4℃),drown the supernatant into different Epidoff tube to measure the protein level and OD.After 24 hours when the agents were given,the same procedure were taken as the time of 2 hours when the agents were given.The OD of SOD,GSH and MDA were measured according to the procedure of kits description Results After 2 hours when the agents were given,SOD activity and MDA in serum,frontal cortex and hippocampus were increased significantly, GSH in these areas were decreased remarkably,compared with the blank group, P＜0.01.The GSH was increased and MDA was decreased notably in propofol group after 2 hours when the agents were given,compared with SE group,P＜0.01. But propofol was not changed the SOD activity augmentation in SE rats. Diazepam,scoplamine and MK801 were not affected on SOD,GSH and MDA both serum and cortex and hippocampus.After 24 hours when the agents were given,SOD activity and MDA in serum,frontal cortex and hippocampus were increased significantly also,GSH in these areas were decreased remarkably, compared with the blank group,P＜0.01.propofol was not changed the SOD activity augmentation in SE rats either.Diazepam,scoplamine and MK801 were not affected on SOD,GSH and MDA in these areas.
Conclusions 1.SOD activity in serum,frontal cortex and hippocampus were increased significantly after 2 hours and 24 hours in SE rats,the MDA was increased also,whereas the GSH was decreased remarkable.2.Propofol can increase GSH and decrease MDA level depression either serum or cortex and hippocampus in SE rats.Our results imply that the inhibition of propofol on Li-pilo induced SE in rats is contribute to its antioxidant properties though down-regulating the MDA and up-regulating GSH level.
引文
[1]Miller LC,Drislane FW.Treatment of status epilepticus.Expert Rev Neurother.2008 Dec;8(12):1817-27.
[2]Epilepsy Foundation of America.Treatment of convulsive status epilepticus: recommendations of the Epilepsy Foundation of America's Working Group on Status Epilepticus.JAMA 1993;270:854-859
[3]Lowenstein DH,Alldredge BK.Status epilepticus.N Engl J Med 1998;338:970-976
[4]Chapman MG,Smith M,Hirsch NP.Status epilepticus[J].Anaesthesia 2001;56:648-659
[5]Lowenstein DH,Bleck T,Macdonald RL.It's time to revise the definition of status epilepticus [J].Epilepsia 1999;40:120-122
[6]Prasad A,Worrall BB.Bertram EH,et al.Propofol and midazolam in the treatment of refractory status epilepticus[J].Epilepsia 2001;42:380-386
[7]Bleck TP.Management approaches to prolonged seizures and status epilepticus[J].Epilepsia 1999;40(suppl):S59-S63
[8]Mayer SA,Claassen J,Lokin J,et al.Refractory status epilepticus:frequency,risk factors,and impact on outcome[J].Arch Neurol,2002,59(2):205-210
[9]Bethmann K,Fritschy JM,Brandt C,Loscher W.Antiepileptic drug resistant rats differ from drug responsive rats in GABA A receptor subunit expression in a model of temporal lobe epilepsy.Neurobiol Dis.2008 Aug;31(2):169-87.
[10]R.M.Freitas,V.S.Nascimento,S.M.Vasconcelos,F.C.Sousa,G.S.Viana and M.M.Fonteles,Catalase activity in cerebellum,hippocampus,frontal cortex and striatum after status epilepticus induced by pilocarpine in Wistar rats.Neurosci.Lett.2004,365:102-105.
[11]L.Turski,C.Ikonomidou,W.A.Turski,Z.A.Bortolotto and E.A.Cavalheiro,Review:cholinergic mechanisms and epileptogenesis.The seizures induced by pilocarpine:a novel experimental model of intractable epilepsy.Synapse 1989,3:154-171.
[12]Clifford,D.B.,Olney,J.W.,Maniotis,A.,Collins,R.C.and Zorumski,C.F.,The functional anatomy and pathology of lithium-pilocarpine and high-dose pilocarpine seizures.Neuroscience.1987.23 3,pp.953-968.
[13]Honchar MP,Olney JW.Sherman WR.Systemic cholinergic agents induce seizures and brain damage in lithium-treated rats.Science,1983.220,.323-334.
[14]Jobe,R.S.,Morrisett,R.A.and Snead,O.C,Characterization of lithium potentiation of pilocarpine-induced status epilepticus in rats.Exp.Neurol.1986,91,pp.471-480.
[15].Morrisett,R.A.,Jope,R.S.and Snead,O.C,1987.Effects of drugs on the initiation and maintenance of status epilepticus induced by administration of pilocarpine to lithium-pretreated rats.Exp.Neurol.97,pp.193-200.
[16]Ormandy,G.C,Jope,R.S.and Snead,O.C.Anticonvulsant actions of MK-801 on the lithium-pilocarpine model of status epilepticus in rats.Exp.Neurol.1989,106:172-180.
[17]Walton,N.Y.,Treiman,D.M.Motor and electroencephalographic response of refractory experimental status epilepticus in rats to treatment with MK-801,diazepam,or MK-801 plus diazepam.Brain Res.1991,553:97-104.
[18]McDonough,J.H.and Shih,T.M.Neuropharmacological mechanisms of nerve agent-induced seizure and neuropathology.Neurosci.Biobehav.Rev.1997,21(5):559-579.
[19]Solberg,Y.and Belkin,M.The role of excitotoxicity in organophosphorous nerve agents central poisoning.TIPS.1997,18(6):183-185.
[20]Lee MG,Chou JY,Lee KH,Choi BJ,Kim SK,Kim CY.MK-801 augments pilocarpine-induced electrographic seizure but protects against brain damage in rats.Prog Neuropsychopharmacol Biol Psychiatry.1997 Feb;21(2):331-344.
[21]Martin ED,Ce(?)a V,Pozo MA.Cholinergic modulation of status epilepticus in the rat barrel field region of primary somatosensory cortex.Exp Neurol,2005 Nov;196(1):120-5.
[22]Ormandy GC,Jope RS,Snead OC Anticonvulsant actions of MK-801 on the lithium-pilocarpine model of status epilepticus in rats.Exp Neurol.1989 Nov;106(2):172-80.
[23]Fujikawa DG.Neuroprotective effect of ketamine administered after status epilepticus onset.Epilepsia,1995 Feb;36(2):186-195.
[24]Ying Z,Babb TL,Comair YG,et al.Induced expression of NMDAR2 proteins and differential expression of NMDAR1 splice variants in dysplastic neurons of human epileptic neocortex.J Neuropathol Exp Neurol 1998;57:47-62
[25]Najm IM,Ying Z,Babb T,et al.Epileptogenocity correlated with increased N-methyl-D-aspartate receptor subunit NR2A/B in human focal cortical dysplasia.Epilepsia 2000;41:971-76
[26]Crino PB,Duhaime AC,Baltuch G,et al.Differential expression of glutamate and GABA-A receptor subunit m-RNA in cortical dysplasia.Neurology 2001;56:906-13
[27]Moddel G,Jacobson B,Ying Z,et al.NMDA receptor NR2B subunit contributes to epileptogenesis in human cortical dysplasia.Brain Res 2005;1046:10-23
[28]Sheng M,Cummings J,Roldan LA,Jan YN,Jan LY.Changing subunit composition of heteromeric NMDA receptors during development of rat cortex.Nature.1994,368:144-147
[29]Monyer H,Burnashev N,Laurie DJ,Sakmann B,Seeburg PH.Developmental and regional expression in the rat brain and functional properties of four NMDA receptors.Neuron 1994,12:529-540.
[30]Al-Ghoul WM,Meeker RB,Greenwood RS.Amygdala kindling alters Af-methyl-D-aspartate receptor subunit messenger RNA expression in the rat supraoptic nucleus.Neuroscience.1997,77:985-992.
[31]Mathern GW,Pretorius JK,Mendoza D,Leite JP,Chimelli L,Born DE,Fried I,Assirati JA,Ojemann GA,Adelson PD,Cahan LD,Kornblum HI.Hippocampal N-mefhyl-D-aspartate receptor subunit mRNA levels in temporal lobe epilepsy patients.Ann Neurol.1999,46:343-358.
[32]DeFazio RA,Hablitz JJ.Alterations in NMDA receptors in a rat model of cortical dysplasia.J Neurophysiol.2000,83:315-321.
[33]Ying Z,Bingaman W,Najm IM.Increased numbers of coassembled PSD-95
18 to NMDA-receptor subunits NR2B and NR1 in human epileptic cortical dysplasia.Epilepsia.2004,45:314-321.
[34]Sperk G,Furtinger S,Schwarzer C,Pirker S.GABA and its receptors in epilepsy.Adv Exp Med Biol.2004,548:92-103.
[35]Cossart R,Bernard C,Ben Ari Y.Multiple facets of GABAergic neurons and synapses:multiple fates of GABA signalling in epilepsies.Trends Neurosci.2005,28:108-115.
[36]Naylor DE,Liu H,Wasterlain CG Trafficking of GABA(A)receptors,loss of inhibition,and a mechanism for pharmacoresistance in status epilepticus[J].J Neurosci.2005 Aug 24;25(34):7724-7733.
[37]Peduto VA,Concas A,Santoro G,et al.Biochemical and electrophysiologic evidence that propofol enhances GABAergic transmission in the rat brain.Anesthesiology 1991;75:1000-9.
[38]Hara M,Kai Y,Ikemoto Y.Propofol activates GABA_A receptor-chloride ionophore complex in dissociated hippocampal pyramidal neurons of the rat.Anesthesiology 1993;79:781-8.
[39]Lin L-H,Chen LL,Zirrolli JA,Harris RA.General anesthetics potentiate-aminobutyric acid actions on 7-aminobutyric acidA receptors expressed by Xenopus oocytes:lack of involvement of intracellular calcium.J Pharmacol Exp Ther 1992;263:569-78.
[40]Orser BA,Bertlik M,Wang L-Y,MacDonald JF.Inhibition by propofol (2,6 di-isopropylphenol)of the 7V-methyl-D-aspartate subtype of glutamate receptor in cultured hippocampal neurones.Br J Pharmacol 1995;116:1761-8.
[41]Yamakura T,Sakimura K,Shimoji K,Mishina M.Effects of propofol on various AMPA-,kainate-and NMDA-selective glutamate receptor channels expressed in Xenopus oocytes.Neurosci Lett 1995;188:187-90.
[42]Buggy DJ,Nicol B,Rowbotham DJ,Lambert DG Effects of intravenous anesthetic agents on glutamate release:a role for GABAA receptor-mediated inhibition.Anesthesiology 2000;92:1067-1073.
[1].Knake S,Hamer HM,Rosenow F.Epilepsy Behav.Status epilepticus:A critical review.2009 Feb 21.
[2]Miller LC,Drislane FW.Treatment of status epilepticus.Expert Rev Neurother.2008 Dec;8(12):1817-1827.
[3]Stecker MM,Kramer TH,Raps EC,et al.Treatment of refractory status epilepticus with propofol:clinical and pharmacokinetic findings[J].Epilepsia 1998;39:18-26
[4]Parviainen I,Uusaro A,Kalviainen R,et al.Propofol in the treatment of refractory status epilepticus.Intensive Care Med[J].2006;32(7):1075-1079.
[5]Rossetti AO,Reichhart MD,Schaller MD,et al.Propofol treatment of refractory status epilepticus:A study of 31 episodes[J].Epilepsia 2004;45:757-763.
[6]Jones P J,Wang Y,Smith MD,et al.Hydroxyamide analogs of propofol exhibit state-dependent block of sodium channels in hippocampal neurons:implications for anticonvulsant activity[J].J Pharmacol Exp Ther.2007 Feb;320(2):828-836.
[7]van Gestel JP,Blusse van Oud-Alblas HJ,Malingre M,et al.Propofol and thiopental for refractory status epilepticus in children[J].Neurology 2005;65:591
[8]Vasile B,Rasulo F,Candiani A,et al.The pathophysiology of propofol infusion syndrome:A simple name for a complex syndrome[J].Intens Care Med 2003;29:1417-1425.
[9]Robinson JD,Melman Y,Walsh EP.Cardiac conduction disturbances and ventricular tachycardia after prolonged propofol infusion in an infant.Pacing Clin Electrophysiol.2008 Aug;31(8):1070-1073
[10]Racine R J.Modification of seizure activity by electrical stimulation.Ⅱ.Motor seizure.Electroencephalogr Clin Neurophysiol[J].1972;32(3):281-294.
[11]Feen ES,Bershad EM,Suarez JI.South Med J.Status epilepticus.2008 Apr;101(4):400-406.
[12]Riss J,Cloyd J,Gates J,Collins S.Benzodiazepines in epilepsy:pharmacology and pharmacokinetics.Acta Neurol Scand 2008:118:69-86.
[13]Nowack WJ,Jordan R.Propofol,seizures and generalized paroxysmal fast activity in the EEG.Clin Electroencephalogr.1994 25(3):110-4.
[14]Walder B,Tramer MR,Seeck M.Seizure-like phenomena and propofol:a systematic review.Neurology.2002 May 14;58(9):1327-1332.
[15]Garg R,Dehan M.Convulsions with propofol:A rare adverse event.J Postgrad Med.2009 Jan-Mar;55(1):69-71.
[16]Zeiler SR,Kaplan PW.Propofol withdrawal seizures (or not).Seizure.2008 17(7):665-7.Epub 2008 May 14.
[17]Hickey KS,Martin DF,Chuidian FX.Propofol-induced seizure-like phenomena.J Emerg Med.2005 Nov;29(4):447-9.
[18]Ide A.Case of amoxapine-induced refractory status epilepticus which was successfully treated with propofol.Chudoku Kenkyu.2006 Oct;19(4):407-8.
[19]Arif H,Hirsch Li.Treatment of status epilepticus.Semin Neurol.2008;28(3):342-354.
[20]Leikin JB,Benigno J,Dubow JS,Fisher M.Status epilepticus due to tiagabine ingestion.Am J Ther.2008 May-Jun;15(3):290-291.
[21]Meyer S,Shamdeen MG,Kegel B,et al.Effect of propofol on seizure-like phenomena and electroencephalographic activity in children with epilepsy vs children with learning difficulties.Anaesthesia.2006 Nov;61(11):1040-1047.
[22]Brenner RP.EEG in convulsive and nonconvulsive status epilepticus.J Clin Neurophysiol.2004 Sep-Oct;21(5):319-31.
[23]Kaplan PW.The EEG of status epilepticus.J Clin Neurophysiol.2006 23(3):221-229.
[24]Tang FR,Chen PM,Tang YC,et al.Two-methyl-6-phenylethynyl-pyridine (MPEP),a metabotropic glutamate receptor 5 antagonist,with low doses of MK801 and diazepam:a novel approach for controlling status epilepticus.Neuropharmacology.2007;53(7):821-31.
[25]Walton NY,Treiman DM.Motor and electroencephalographic response of refractory experimental status epilepticus in rats to treatment with MK-801,diazepam,or MK-801 plus diazepam.Brain Res.1991 Jul 5;553(1):97-104.
[26]王恒林,曹江北,王卓强,等。丙泊酚对N-甲基-D-天冬氨酸所致PC12细胞损伤的保护作用。中国药理学与毒理学杂志,2003,17(3):202-203
[27]Ying SW,Goldstein PA.Propofol suppresses synaptic responsiveness of somatosensory relay neurons to excitatory input by potentiating GABAA receptor chloride channels.Mol Pain.2005 Jan 14;1(1):2-12.
[28]Honegger P,Matthieu JM.Selective toxicity of the general anesthetic propofol for GABAergic neurons in rat brain cell cultures[J].J Neurosci Res,1996,45(5):631-636.
[29]Ozt(u｜¨)rk E,Demirbilek S,K(o｜¨)ro(?)lu A,et al.Propofol and erythopoietin antioxidant properties in rat brain injured tissue.Prog Neuropsychopharmacol Biol Psychiatry.2008;32(1):81-86.
[30]Kinirons P,Doherty CP.Status epilepticus:a modern approach to management.Eur J Emerg Med.2008 Aug;15(4):187-195
[1]Rasmussen PA,Yang Y,Rutecki PA.Propofol inhibits epileptiform activity in rat hippocampal slices.Epilepsy Res.1996 Nov;25(3):169-75.
[2]Leander JD,Lawson RR,Ornstein PL,et al.N-methyl-D-aspartic acid-lethality in mice:Selective antagonism by phencyclidine-like drugs.Brain Res,1988,448:115-120
[3]John H,McDonough JR,Shih TM.A study of the N-methyl-D-aspartate antagonistic properties of anticholinergic drugs.Pharmacology Biochemistry and Behavior,1995,51:249-253
[4]Kelsey JE,Sanderson KL,Frye CA.Perforant path stimulation in rats produces seizures,loss of hippocampal neurons,and a deficit in spatial mapping which are reduced by prior MK-801.Behav Brain Res.2000 Jan;107(1-2):59-69.
[5]Lukomskaya NY,Rukoyatkina NI,Gorbunova LV,et al.Studies of the roles of NMDA and AMPA glutamate receptors in the mechanism of corasole convulsions in mice.Neurosci Behav Physiol.2004 Oct;34(8):783-9.
[6]Lukomskaia NIa,Rukoiatkina NI,Gorbunova LV,et al.Role of NMDA and AMPA glutamate receptors in the mechanism of korazol-induced convulsions in mice.Ross Fiziol Zh Im I M Sechenova.2003 Mar;89(3):292-301.
[7]Ohmori H,Sato Y,Namiki A.The anticonvulsant action of propofol on epileptiform activity in rat hippocampal slices.Anesth Analg.2004 Oct;99(4):1095-1101
[8]Feiner JR,Bickler PE,Estrada S,Mild hypothermia,but not propofol,is neuroprotective in organotypic hippocampal cultures.Anesth Analg,2005 Jan;100(1):215-25.
[9]Yamakura T,Sakimura K,Shimoji K,et al.Effects of propofol on various AMPA-,kainate-and NMDA-selective glutamate receptor channels expressed inXenopus oocytes.Neurosci Lett.1995 Mar 31;188(3):187-90.
[10]Orser BA,Bertlik M,Wang LY,et al.Inhibition by propofol (2,6 di-isopropylphenol)of the N-methyl-D-aspartate subtype of glutamate receptor in cultured hippocampal neurones.Br J Pharmacol.1995 Sep;116(2):1761-1768.
[11]Hans P,Bonhomme V,Collette J,et al.Propofol protects cultured rat hippocampal neurons against N-methyl-D-aspartate receptor-mediated glutamate toxicity.J Neurosurg Anesthesiol.1994 Oct;6(4):249-53.
[12]Kingston S,Mao L,Yang L,et al.Propofol inhibits phosphorylation of N-methyl-D-aspartate receptor NRl subunits in neurons.Anesthesiology.2006 Apr;104(4):763-769.
[13]Fibuch EE,Wang JQ.Inhibition of the MAPK/ERK cascade:a potential transcription-dependent mechanism for the amnesic effect of anesthetic propofol.Neurosci Bull.2007 Mar;23(2):l 19-24.
[14]Kozinn J,Mao L,Arora A,et al.Inhibition of glutamatergic activation of extracellular signal-regulated protein kinases in hippocampal neurons by the intravenous anesthetic propofol.Anesthesiology.2006 Dec;105(6):1182-91.
[1].韩济生主编.神经学原理,第二版,北京:北京医科大学出版社,1998:527:1077
[2]Sheng M,Cummings J,Roldan LA,Jan YN,Jan LY.Changing subunit composition of heteromeric NMDA receptors during development of rat cortex.Nature.1994,368:144-147
[3]Monyer H,Burnashev N,Laurie DJ,Sakmann B,Seeburg PH.Developmental and regional expression in the rat brain and functional properties of four NMDA receptors.Neuron 1994,12:529-540.
[4]Al-Ghoul WM,Meeker RB,Greenwood RS.Amygdala kindling alters N-methyl-D-aspartate receptor subunit messenger RNA expression in the rat supraoptic nucleus.Neuroscience.1997,77:985-992.
[5]Mathern GW,Pretorius JK,Mendoza D,Leite JP,Chimelli L,Born DE,Fried I,Assirati JA,Ojemann GA,Adelson PD,Cahan LD,Komblum HI.Hippocampal N-methyl-D-aspartate receptor subunit mRNA levels in temporal lobe epilepsy patients.Ann Neurol.1999,46:343-358.
[6]DeFazio RA,Hablitz JJ.Alterations in NMDA receptors in a rat model of cortical dysplasia.J Neurophysiol.2000,83:315-321.
[7]Ying Z,Bingaman W,Najm IM.Increased numbers of coassembled PSD-95 to NMDA-receptor subunits NR2B and NR1 in human epileptic cortical dysplasia.Epilepsia.2004,45:314-321.
[8]Najm IM,Ying Z,Babb T,et al.Epileptogenocity correlated with increased N-methyl-D-aspartate receptor subunit NR2A/B in human focal cortical dysplasia.Epilepsia 2000;41:971-76
[9]Crino PB,Duhaime AC,Baltuch G,et al.Differential expression of glutamate and GABA-A receptor subunit m-RNA in cortical dysplasia.Neurology 2001;56:906-13
[10]Moddel Q Jacobson B,Ying Z,et al.NMDA receptor NR2B subunit contributes to epileptogenesis in human cortical dysplasia.Brain Res 2005;1046:10-23
[11]Kotani Y,Shimazawa M,Yoshimura S,Iwama T,Hara H.The experimental and clinical pharmacology of propofol,an anesthetic agent with neuroprotective properties.CNS Neurosci Ther.2008;14(2):95-106.
[12]Fibuch EE,Wang JQ.Inhibition of the MAPK/ERK cascade:a potential transcription-dependent mechanism for the amnesic effect of anesthetic propofol.Neurosci Bull.2007 Mar;23(2):l 19-24.
[13]Kozinn J,Mao L,Arora A,Yang L,Fibuch EE,Wang JQ.Inhibition of glutamatergic activation of extracellular signal-regulated protein kinases in hippocampal neurons by the intravenous anesthetic propofol.Anesthesiology,2006 Dec;105(6):l 182-1191.
[14]Racine R J.Modification of seizure activity by electrical stimulation.Ⅱ.Motor seizure.Electroencephalogr Clin Neurophysiol[J].1972;32(3):281-294.
[15]Sheng M,Cummings J,Roldan LA,Jan YN,Jan LY.Changing subunit composition of heteromeric NMDA receptors during development of rat cortex.Nature.1994,368:144-147
[16]Monyer H,Burnashev N,Laurie DJ,Sakmann B,Seeburg PH.Developmental and regional expression in the rat brain and functional properties of four NMDA receptors.Neuron 1994,12:529-540.
[17]Chen Q,He S,Hu XL,et al.Differential roles of NR2A- and NR2B-containing NMDA receptors in activity-dependent brain-derived neurotrophic factor gene regulation and limbic epileptogenesis.J Neurosci.2007 Jan 17;27(3):542-552.
[18]Huo JZ,Dykstra CM,Gurd JW.Neurosci Lett.Increase in tyrosine phosphorylation of the NMDA receptor following the induction of status epilepticus.2006 Jul 3;401(3):266-270.
[19]Yang J,Woodhall GL,Jones RS.Tonic facilitation of glutamate release by presynaptic NR2B-containing NMDA receptors is increased in the entorhinal cortex of chonically epileptic rats.J Neurosci.2006;26(2):406-410.
[20]Borb(?)ly S,Dob(?)E,Cz(?)g(?) D,et al.Modification of ionotropic glutamate receptor-mediated processes in the rat hippocampus following repeated,brief seizures.Neuroscience.2009 Mar 3;159(1):358-368.
[21]王恒林,曹江北,王卓强,等。丙泊酚对N-甲基-D-天冬氨酸所致PC12细胞损伤的保护作用。中国药理学与毒理学杂志,2003,17(3):202-203
[22]Grasshoff C,Gillessen T.Effects of propofol on N-methyl-D-aspartate receptor-mediated calcium increase in cultured rat cerebrocortical neurons.Eur J Anaesthesiol.2005 Jun;22(6):467-470
[23]Fibuch EE,Wang JQ.Inhibition of the MAPK/ERK cascade:a potential transcription-dependent mechanism for the amnesic effect of anesthetic propofol.Neurosci Bull.2007 Mar;23(2):119-124.
[24]Kingston S,Mao L,Yang L,et al.Propofol inhibits phosphorylation of N-methyl-D-aspartate receptor NRl subunits in neurons.Anesthesiology.2006;104(4):763-769.
[1]Gibbs JW,Shumate MD,Coulter DA.Differential epilepsy-associated alterations in postsynaptic GABAA receptor function in dentate granule and CAl neurons.J Neurophysiol 1997;77:1924-1938.
[2]Mangan PS,Bertram EH.Shortened-duration GABA(A) receptor-mediated synaptic potentials underlie enhanced CAl excitability in a chonic model of temporal lobe epilepsy.Neuroscience 1997;80:1101-1111.
[3]Galanopoulou AS.Developmental patterns in the regulation of chloride homeostasis and GABA(A) receptor signaling by seizures.Epilepsia.2007;48Suppl 5:14-8.
[4]Volk HA,Arabadzisz D,Fritschy JM,et al.Neurobiol Dis.Antiepileptic drug-resistant rats differ from drug-responsive rats in hippocampal neurodegeneration and GABA(A) receptor ligand binding in a model of temporal lobe epilepsy.2006;21(3):633-46.
[5]Martella G,De Persis C,Bonsi P,et al.Inhibition of persistent sodium current fraction and voltage-gated L-type calcium current by propofol in cortical neurons:implications for its antiepileptic activity.Epilepsia.2005;46(5):624-35.
[6]Gilby KL,Da Silva AG,McIntyre DC.Differential GABA(A) subunit expression following status epilepticus in seizure-prone and seizure-resistant rats:a putative mechanism for refractory drug response.Epilepsia.2005;46 Suppl 5:3-9.
[7]Raol YH,Lund IV,Bandyopadhyay S,et al.Enhancing GABA(A) receptor alpha 1 subunit levels in hippocampal dentate gyrus inhibits epilepsy development in an animal model of temporal lobe epilepsy.J Neurosci.2006;26(44):11342-11346.
[8]Bethmann K,Fritschy JM,Brandt C,L(o｜¨)scher W.Antiepileptic drug resistant rats differ from drug responsive rats in GABA A receptor subunit expression in a model of temporal lobe epilepsy.Neurobiol Dis.2008 Aug;31(2):169-87.
[9]Orser BA,Canning K J,Macdonald JF.Mechanisms of general anesthesia.Curr Opin Anaesthesiol.2002 Aug;15(4):427-33.
[10]Sebel LE,Richardson JE,Singh SP,Bell SV,Jenkins A.Additive effects of sevoflurane and propofol on gamma-aminobutyric acid receptor function.Anesthesiology.2006 Jun;104(6):1176-83.
[11]Rasmussen PA,Yang Y,Rutecki PA.Propofol inhibits epileptiform activity in rat hippocampal slices.Epilepsy Res.1996 Nov;25(3):169-75.
[12]王恒林,米卫东,赵从,等。丙泊酚对毒鼠强诱发大鼠SE的抑制作用及其皮层GABA受体α1亚单位表达的影响,军医进修学院学报,2009;
[13]Feng H J,Macdonald RL.Multiple actions of propofol on alphabetagamma and alphabetadelta GABAA receptors.Mol Pharmacol.2004Dec;66(6):1517-24.
[14]Lam DW,Reynolds JN.Modulatory and direct effects of propofol on recombinant GABAA receptors expressed in xenopus oocytes:influence of alpha- and gamma2-subunits.Brain Res.1998 Feb 16;784(1-2):179-87.
[15]Uchida I,Li L,Yang J.The role of the GABA(A) receptor alphal subunit N-terminal extracellular domain in propofol potentiation of chloride current.Neuropharmacology.1997 Nov-Dec;36(11-12):1611-21.
[1]Costa M.S.Rocha J.B.Perosa S.R.Cavalheiro E.A.Naffah-Mazzacoratti M.G.Pilocarpine-induced status epilepticus increases glutamate release in rat hippocampal synaptosomes,Neurosci.Lett.2004,356:41-44.
[2]Tejada S,Roca C,Sureda A,et al.Antioxidant response analysis in the brain after pilocarpine treatments.Brain Res Bull.2006 May 15;69(5):587-592.
[3]Chuang YC,Chen SD,Lin TK,et al.Upregulation of nitric oxide synthase Ⅱcontributes to apoptotic cell death in the hippocampal CA3 subfield via a cytochome c/caspase-3 signaling cascade following induction of experimental temporal lobe status epilepticus in the rat.Neuropharmacology.2007Apr;52(5):1263-73.
[4]Liang LP,Patel M.Seizure-induced changes in mitochondrial redox status.Free Radic Biol Med.2006 Jan 15;40(2):316-22.
[5]Kovács R,Schuchmann S,Gabriel S,et al.Free radical-mediated cell damage after experimental status epilepticus in hippocampal slice cultures.J Neurophysiol.2002 Dec;88(6):2909-18.
[6]Kobayashi K,Yoshino F,Takahashi SS,Direct assessments of the antioxidant effects of propofol medium chain triglyceride/long chain triglyceride on the brain of stroke-prone spontaneously hypertensive rats using electron spin resonance spectroscopy.Anesthesiology.2008 Sep;109(3):426-35.
[7]Ozt(u｜¨)rk E,Demirbilek S,K(O｜¨)ro(g｜ˇ)lu A,Propofol and erythopoietin antioxidant properties in rat brain injured tissue.Prog Neuropsychopharmacol Biol Psychiatry.2008 Jan 1;32(1):81-6
[8]Daskalopoulos R,Korcok J,Tao L,Accumulation of intracellular ascorbate from dehydroascorbic acid by astrocytes is decreased after oxidative stress and restored by propofol.Glia.2002 Aug;39(2):124-32.
[9]Bayona NA,Gelb AW,Jiang Z,et al.Propofol neuroprotection in cerebral ischemia and its effects on low-molecular-weight antioxidants and skilled motor tasks.Anesthesiology.2004 May;100(5):1151-9.
[10]Lee Y,Chung C,Oh YS.Effectiveness of propofol pretreatment on the extent of deranged cerebral mitochondrial oxidative enzyme system after incomplete forebrain ischemia/reperfusion in rats.J Korean Med Sci.2000 Dec;15(6):627-30.
[11]Young Y,Menon DK,Tisavipat N,et al.Propofol neuroprotection in a rat model of ischaemia reperfusion injury.Eur J Anaesthesiol.1997 May;14(3):320-6.
[12]Racine R J.Modification of seizure activity by electrical stimulation.Ⅱ.Motor seizure.Electroencephalogr ClinNeurophysiol[J].1972;32(3):281-294.
[13]Westman N,Marklund S.L.Copper and zinc containing superoxide dismutase and manganese containing superoxide dismutase in human tissues and human malignant tumors,1982,Cancer Res 41:2962-2966.
[14]Freitas,S.M.Vasconcelos,F.C.Souza,G.S.et al.Oxidative stress in the hippocampus after pilocarpine-induced status epilepticus in Wistar rats,FEBS J.2005,272,1307-1312.
[15]Yu X,Shao XG,Sun H,Activation of cerebral peroxisome proliferator-activated receptors gamma exerts neuroprotection by inhibiting oxidative stress following pilocarpine-induced status epilepticus.Brain Res.2008 Mar 20;1200:146-58.
[16]Tejada S,Sureda A,Roca C,Gamundi A,Esteban S.Antioxidant response and oxidative damage in brain cortex after high dose of pilocarpine.Brain Res Bull.2007 Jan 9;71(4):372-5.
[17]Rajasekaran K.Seizure-induced oxidative stress in rat brain regions:blockade by nNOS inhibition.Pharmacol Biochem Behav.2005 Feb;80(2):263-72.
[18]Sleven HJ,Gibbs JE,Cock H.The antioxidant N-acetyl-L-cysteine does not prevent hippocampal glutathione loss or mitochondrial dysfunction associated with status epilepticus.Epilepsy Res.2006 May;69(2):165-9.
[19]Anderson MF,Nilsson M,Sims NR.Glutathione monoethylester prevents mitochondrial glutathione depletion during focal cerebral ischemia.Neurochem Int.2004 Feb;44(3):153-9.
[20]Riischenschmidt C,Chen J,Becker A,Riazanski V,Beck H.Functional properties and oxidative modulation of A-type K currents in hippocampal granule cells of control and chonically epileptic rats.Eur J Neurosci.2006 Feb;23(3):675-85.
[21]Sleven H,Gibbs JE,Heales S,Thorn M,Cock H.Depletion of reduced glutathione precedes inactivation of mitochondrial enzymes following limbic status epilepticus in the rat hippocampus.Neurochem Int.2006 Jan;48(2):75-82.
[22]Klaidman LK,Adams JD Jr,Cross R,Pazdernik TL,Samson F.Alterations in brain glutathione homeostasis induced by the nerve gas soman.Neurotox Res.2003;5(3):177-82.
[23]George B,Kulkarni SK.Dopaminergic modulation of lithium/pilocarpineinduced status epilepticus in rats.Methods Find Exp Clin Pharmacol.1997Sep;19(7):481-8.
[24]Dal-Pizzol F,Klamt F,Vianna MM,Schoder N,Quevedo J,Benfato MS,Moreira JC,Walz R.Lipid peroxidation in hippocampus early and late after status epilepticus induced by pilocarpine or kainic acid in Wistar rats.Neurosci Lett.2000 Sep 22;291(3):179-82.
[25]Liu ZW,Zhang T,Yang Z.Involvement of nitric oxide in spatial memory deficits in status epilepticus rats.Neurochem Res.2007 Nov;32(l l):1875-83.
[26]Gupta YK,Briyal S.Protective effect of vineatrol against kainic acid induced seizures,oxidative stress and on the expression of heat shock proteins in rats.Eur Neuropsychopharmacol.2006 Feb;16(2):85-91.
[27]Santos LF,Freitas RL,Xavier SM,Saldanha GB,Freitas RM.Neuroprotective actions of vitamin C related to decreased lipid peroxidation and increased catalase activity in adult rats after pilocarpine-induced seizures.Pharmacol Biochem Behav.2008;89(1):1-5.
[28]Kobayashi K,Yoshino F,Takahashi SS,Todoki K,Maehata Y,Komatsu T,Yoshida K,Lee MC.Direct assessments of the antioxidant effects of propofol medium chain triglyceride/long chain triglyceride on the brain of stroke-prone spontaneously hypertensive rats using electron spin resonance spectroscopy.Anesthesiology.2008;109(3):426-435.
[29]Vansant G,Trauger RJ,Cameron A,Vendemelio M,Kreitschitz S,Carlo AT,Banaszczyk MG,Carlo DJ,Hendler S.Propofol hemisuccinate suppression of experimental autoimmune encephalomyelitis.Autoimmunity.2007;40(3):180-186.
[30]Acquaviva R,Campisi A,Murabito P,Raciti G,Avola R,Mangiameli S,Musumeci I,Barcellona ML,Vanella A,Li Volti G.Propofol attenuates peroxynitrite-mediated DNA damage and apoptosis in cultured astrocytes:an alternative protective mechanism.Anesthesiology.2004;101 (6):1363-1371.
[31]Bayona NA,Gelb AW,Jiang Z,Wilson JX,Urquhart BL,Cechetto DF.Propofol neuroprotection in cerebral ischemia and its effects on low-molecular-weight antioxidants and skilled motor tasks.Anesthesiology.2004;100(5):1151-9.
[32]Lee Y,Chung C,Oh YS.Effectiveness of propofol pretreatment on the extent of deranged cerebral mitochondrial oxidative enzyme system after incomplete forebrain ischemia/reperfusion in rats.J Korean Med Sci.2000;15(6):627-630.
[33]Ozturk E,Demirbilek S,Kadir But A,Saricicek V,Gulec M,Akyol O,Ozcan Ersoy M.Antioxidant properties of propofol and erythopoietin after closed head injury in rats.Prog Neuropsychopharmacol Biol Psychiatry.2005 Jul;29(6):922-7.
[34]Ozturk E,Demirbilek S,Koroglu A,But A,Begec ZO,Gulec M,Akyol O,Ersoy MO.Propofol and erythopoietin antioxidant properties in rat brain injured tissue.Prog Neuropsychopharmacol Biol Psychiatry.2008 Jan 1;32(1):81-86.
[35]Ceylan BG,Yilmaz F,Eroglu F,Yavuz L,Gulmen S,Vural H.Oxidant and antioxidant activities of different anesthetic techniques.Propofol versus desflurane.Saudi Med J.2009 Mar;30(3):371-6.
[36]Cinnella G,Vendemiale G,Dambrosio M,Serviddio G,Pugliese PL,Aspromonte G,Altomare E.Effect of Propofol,Sevoflurane and Desflurane on systemic redox balance.Int J Immunopathol Pharmacol.2007;20(3):585-93.
[37]Peterson SL,Purvis RS,Griffith JW.Comparison of neuroprotective effects induced by alpha-phenyl-N-tert-butyl nitrone(PBN) and N-tert-butyl-alpha-(2sulfophenyl) nitrone(S-PBN) in lithium-pilocarpine status epilepticus.Neurotoxicology.2005 Dec;26(6):969-79.
[1]Epilepsy Foundation of America.Treatment of convulsive status epilepticus:recommendations of the Epilepsy Foundation of America's Working Group on Status Epilepticus.JAMA 1993;270:854-859
[2]Lowenstein DH,Alldredge BK.Status epilepticus.N Engl J Med 1998;338:970-976
[3]Chapman MG,Smith M,Hirsch NP.Status epilepticus[J].Anaesthesia 2001;56:648-659
[4]Lowenstein DH,Bleck T,Macdonald RL.It's time to revise the definition of status epilepticus[J].Epilepsia 1999;40:120-122
[5]Prasad A,Worrall BB.Bertram EH,et al.Propofol and midazolam in the treatment of refractory status epilepticus[J].Epilepsia 2001;42:380-386
[6]Bleck TP.Management approaches to prolonged seizures and status epilepticus[J].Epilepsia 1999;40(suppl):S59-S63
[7]Mayer SA,Claassen J,Lokin J,et al.Refractory status epilepticus:frequency,risk factors,and impact on outcome[J].Arch Neurol,2002,59(2):205-210
[9]Garzon E,Fernandez RM,Sakamoto AC.Analysis of clinical characteristics and risk factors for mortality in human status epilepticus[J].Seizure 2003;12:337-345.
[10]Stecker MM,Kramer TH,Raps EC,et al.Treatment of refractory status epilepticus with propofol:clinical and pharmacokinetic findings[J].Epilepsia 1998;39:18-26
[11]Parviainen I,Uusaro A,Kalviainen R,et al.Propofol in the treatment of refractory status epilepticus.Intensive Care Med.2006;32(7):1075-1079.
[12]Rossetti AO,Reichhart MD,Schaller MD,et al.Propofol treatment of refractory status epilepticus:A study of 31 episodes[J].Epilepsia 2005;45:757-763.
[13]Jones P J,Wang Y,Smith MD,et al.Hydroxyamide analogs of propofol exhibit state-dependent block of sodium channels in hippocampal neurons:implications for anticonvulsant activity[J].J Pharmacol Exp Ther.2007Feb;320(2):828-836.
[14]付秀全,吴宏涛.丙泊酚和硫喷妥钠治疗难治性SE18例疗效观察.实用临床医院杂志,2005,4(2):55-56
[15]朱育昌,许志恩.不同药物治疗难治性全面性SE的疗效分析.吉林医学,2005,26(8):837-838
[16]van Gestel JP,Blusse van Oud-Alblas H J,Malingre M,et al.Propofol and thiopental for refractory status epilepticus in children.Neurology 2005;65:591-592.
[17]周力文,赵贺堂,张世杰.丙泊酚持续静滴治疗小儿SE的临床观察.中国实用儿科杂志,2005,3(20):173-174
[18]Naylor DE,Liu H,Wasterlain CG.Trafficking of GABA(A) receptors,loss of inhibition,and a mechanism for pharmacoresistance in status epilepticus[J].J Neurosci.2005 Aug 24;25(34):7724-7733.
[19]Ying SW,Goldstein PA.Propofol suppresses synaptic responsiveness of somatosensory relay neurons to excitatory input by potentiating GABAA receptor chloride channels[J].Mol Pain.2005;14;1(1):2-12.
[20]Smith I,White PF,Nathanson M,et al.Propofol:an update on its clinical use.Anesthesiology 1994;81:1005-1043
[21]Hara M,Kai Y,Ikemoto Y.Propofol activates GABAA receptor-chloride ionophore complex in dissociated hippocampal pyramidal neurons of the rat.Anesthesiology 1993;79:781-788
[22]Fujikawa DG.Prolonged seizures and cellular injury:Understanding the connections[J].Epilepsy Behav 2005;7:S3-11
[23]Rice AC,DeLorenzo RJ.NMDA receptor activation during status epilepticus is required for the development of epilepsy.Brain Res 1998;782:240-247
[24]Pal S,Sombati S,Limbrick DD Jr,et al.In vitro status epilepticus causes sustained elevation of intracellular calcium levels in hippocampal neurons[J].Brain Res 1999;851:20-31
[25]Murthy JMK.Refractory status epilepticus[J].Neurol India 2006;54:354-358
[26]王恒林,曹江北,王卓强,等.丙泊酚对N-甲基-D-天冬氨酸所致PC12细胞损伤的保护作用.中国药理学与毒理学杂志2003;17(3):202-205
[27]Agrawal N,Alonso A,Ragsdale DS.Increased persistent sodium currents in rat entorhinal cortex layer V neurons in a post-status epilepticus model of temporal lobe epilepsy.Epilepsia 2003;44:1601-1604
[28]Martella G,De Persis C,Bonsi P,et al.Inhibition of persistent sodium current fraction and voltage-gated L-type calcium current by propofol in cortical neurons:implications for its anti-epileptic activity.Epilepsia 2005;46:624-635.
[29]Vasile B,Rasulo F,Candiani A,et al.The pathophysiology of propofol infusion syndrome:A simple name for a complex syndrome.Intens Care Med 2003;29:1417-1425.
[30]Marik PE.Propofol:therapeutic indications and side-effects.Curr Pharm Des 2004;10:3639-3649.
[31]Sabsovich I,Rehman Z,Yunen J,Propofol infusion syndrome:a case of increasing morbidity with traumatic brain injury.Am J Crit Care.2007Jan;16(1):82-85.
[32]Vasile B,Rasulo F,Candiani A,et al.The pathophysiology of propofol infusion syndrome:a simple name for a complex syndrome.Intensive Care Med 2003;29:1417-1425
[33]Kang TM.Propofol infusion syndrome in critically ill patients.Ann Pharmacother 2002;36:1453-1456
[34]McKeage K,Perry CM.Propofol:a review of its use in intensive care sedation of adults.CNS Drugs 2003;17:235-272
[35]Short TG,Young Y Toxicity of intravenous anaesthetics.Best Pract Res Clin Anaesthesiol 2003;17:77-89
[36]Cornfield DN,Tegtmeyer K,Nelson MD,Milla CE,Sweeney M.Continuous profol infusion in 142 critically ill children.Pediatrics 2002;110:1177-1181.
[2]Epilepsy Foundation of America.Treatment of convulsive status epilepticus: recommendations of the Epilepsy Foundation of America's Working Group on Status Epilepticus.JAMA 1993;270:854-859
[3]Lowenstein DH,Alldredge BK.Status epilepticus.N Engl J Med 1998;338:970-976
[4]Chapman MG,Smith M,Hirsch NP.Status epilepticus[J].Anaesthesia 2001;56:648-659
[5]Lowenstein DH,Bleck T,Macdonald RL.It's time to revise the definition of status epilepticus [J].Epilepsia 1999;40:120-122
[6]Prasad A,Worrall BB.Bertram EH,et al.Propofol and midazolam in the treatment of refractory status epilepticus[J].Epilepsia 2001;42:380-386
[7]Bleck TP.Management approaches to prolonged seizures and status epilepticus[J].Epilepsia 1999;40(suppl):S59-S63
[8]Mayer SA,Claassen J,Lokin J,et al.Refractory status epilepticus:frequency,risk factors,and impact on outcome[J].Arch Neurol,2002,59(2):205-210
[9]Bethmann K,Fritschy JM,Brandt C,Loscher W.Antiepileptic drug resistant rats differ from drug responsive rats in GABA A receptor subunit expression in a model of temporal lobe epilepsy.Neurobiol Dis.2008 Aug;31(2):169-87.
[10]R.M.Freitas,V.S.Nascimento,S.M.Vasconcelos,F.C.Sousa,G.S.Viana and M.M.Fonteles,Catalase activity in cerebellum,hippocampus,frontal cortex and striatum after status epilepticus induced by pilocarpine in Wistar rats.Neurosci.Lett.2004,365:102-105.
[11]L.Turski,C.Ikonomidou,W.A.Turski,Z.A.Bortolotto and E.A.Cavalheiro,Review:cholinergic mechanisms and epileptogenesis.The seizures induced by pilocarpine:a novel experimental model of intractable epilepsy.Synapse 1989,3:154-171.
[12]Clifford,D.B.,Olney,J.W.,Maniotis,A.,Collins,R.C.and Zorumski,C.F.,The functional anatomy and pathology of lithium-pilocarpine and high-dose pilocarpine seizures.Neuroscience.1987.23 3,pp.953-968.
[13]Honchar MP,Olney JW.Sherman WR.Systemic cholinergic agents induce seizures and brain damage in lithium-treated rats.Science,1983.220,.323-334.
[14]Jobe,R.S.,Morrisett,R.A.and Snead,O.C,Characterization of lithium potentiation of pilocarpine-induced status epilepticus in rats.Exp.Neurol.1986,91,pp.471-480.
[15].Morrisett,R.A.,Jope,R.S.and Snead,O.C,1987.Effects of drugs on the initiation and maintenance of status epilepticus induced by administration of pilocarpine to lithium-pretreated rats.Exp.Neurol.97,pp.193-200.
[16]Ormandy,G.C,Jope,R.S.and Snead,O.C.Anticonvulsant actions of MK-801 on the lithium-pilocarpine model of status epilepticus in rats.Exp.Neurol.1989,106:172-180.
[17]Walton,N.Y.,Treiman,D.M.Motor and electroencephalographic response of refractory experimental status epilepticus in rats to treatment with MK-801,diazepam,or MK-801 plus diazepam.Brain Res.1991,553:97-104.
[18]McDonough,J.H.and Shih,T.M.Neuropharmacological mechanisms of nerve agent-induced seizure and neuropathology.Neurosci.Biobehav.Rev.1997,21(5):559-579.
[19]Solberg,Y.and Belkin,M.The role of excitotoxicity in organophosphorous nerve agents central poisoning.TIPS.1997,18(6):183-185.
[20]Lee MG,Chou JY,Lee KH,Choi BJ,Kim SK,Kim CY.MK-801 augments pilocarpine-induced electrographic seizure but protects against brain damage in rats.Prog Neuropsychopharmacol Biol Psychiatry.1997 Feb;21(2):331-344.
[21]Martin ED,Ce(?)a V,Pozo MA.Cholinergic modulation of status epilepticus in the rat barrel field region of primary somatosensory cortex.Exp Neurol,2005 Nov;196(1):120-5.
[22]Ormandy GC,Jope RS,Snead OC Anticonvulsant actions of MK-801 on the lithium-pilocarpine model of status epilepticus in rats.Exp Neurol.1989 Nov;106(2):172-80.
[23]Fujikawa DG.Neuroprotective effect of ketamine administered after status epilepticus onset.Epilepsia,1995 Feb;36(2):186-195.
[24]Ying Z,Babb TL,Comair YG,et al.Induced expression of NMDAR2 proteins and differential expression of NMDAR1 splice variants in dysplastic neurons of human epileptic neocortex.J Neuropathol Exp Neurol 1998;57:47-62
[25]Najm IM,Ying Z,Babb T,et al.Epileptogenocity correlated with increased N-methyl-D-aspartate receptor subunit NR2A/B in human focal cortical dysplasia.Epilepsia 2000;41:971-76
[26]Crino PB,Duhaime AC,Baltuch G,et al.Differential expression of glutamate and GABA-A receptor subunit m-RNA in cortical dysplasia.Neurology 2001;56:906-13
[27]Moddel G,Jacobson B,Ying Z,et al.NMDA receptor NR2B subunit contributes to epileptogenesis in human cortical dysplasia.Brain Res 2005;1046:10-23
[28]Sheng M,Cummings J,Roldan LA,Jan YN,Jan LY.Changing subunit composition of heteromeric NMDA receptors during development of rat cortex.Nature.1994,368:144-147
[29]Monyer H,Burnashev N,Laurie DJ,Sakmann B,Seeburg PH.Developmental and regional expression in the rat brain and functional properties of four NMDA receptors.Neuron 1994,12:529-540.
[30]Al-Ghoul WM,Meeker RB,Greenwood RS.Amygdala kindling alters Af-methyl-D-aspartate receptor subunit messenger RNA expression in the rat supraoptic nucleus.Neuroscience.1997,77:985-992.
[31]Mathern GW,Pretorius JK,Mendoza D,Leite JP,Chimelli L,Born DE,Fried I,Assirati JA,Ojemann GA,Adelson PD,Cahan LD,Kornblum HI.Hippocampal N-mefhyl-D-aspartate receptor subunit mRNA levels in temporal lobe epilepsy patients.Ann Neurol.1999,46:343-358.
[32]DeFazio RA,Hablitz JJ.Alterations in NMDA receptors in a rat model of cortical dysplasia.J Neurophysiol.2000,83:315-321.
[33]Ying Z,Bingaman W,Najm IM.Increased numbers of coassembled PSD-95
18 to NMDA-receptor subunits NR2B and NR1 in human epileptic cortical dysplasia.Epilepsia.2004,45:314-321.
[34]Sperk G,Furtinger S,Schwarzer C,Pirker S.GABA and its receptors in epilepsy.Adv Exp Med Biol.2004,548:92-103.
[35]Cossart R,Bernard C,Ben Ari Y.Multiple facets of GABAergic neurons and synapses:multiple fates of GABA signalling in epilepsies.Trends Neurosci.2005,28:108-115.
[36]Naylor DE,Liu H,Wasterlain CG Trafficking of GABA(A)receptors,loss of inhibition,and a mechanism for pharmacoresistance in status epilepticus[J].J Neurosci.2005 Aug 24;25(34):7724-7733.
[37]Peduto VA,Concas A,Santoro G,et al.Biochemical and electrophysiologic evidence that propofol enhances GABAergic transmission in the rat brain.Anesthesiology 1991;75:1000-9.
[38]Hara M,Kai Y,Ikemoto Y.Propofol activates GABA_A receptor-chloride ionophore complex in dissociated hippocampal pyramidal neurons of the rat.Anesthesiology 1993;79:781-8.
[39]Lin L-H,Chen LL,Zirrolli JA,Harris RA.General anesthetics potentiate-aminobutyric acid actions on 7-aminobutyric acidA receptors expressed by Xenopus oocytes:lack of involvement of intracellular calcium.J Pharmacol Exp Ther 1992;263:569-78.
[40]Orser BA,Bertlik M,Wang L-Y,MacDonald JF.Inhibition by propofol (2,6 di-isopropylphenol)of the 7V-methyl-D-aspartate subtype of glutamate receptor in cultured hippocampal neurones.Br J Pharmacol 1995;116:1761-8.
[41]Yamakura T,Sakimura K,Shimoji K,Mishina M.Effects of propofol on various AMPA-,kainate-and NMDA-selective glutamate receptor channels expressed in Xenopus oocytes.Neurosci Lett 1995;188:187-90.
[42]Buggy DJ,Nicol B,Rowbotham DJ,Lambert DG Effects of intravenous anesthetic agents on glutamate release:a role for GABAA receptor-mediated inhibition.Anesthesiology 2000;92:1067-1073.
[1].Knake S,Hamer HM,Rosenow F.Epilepsy Behav.Status epilepticus:A critical review.2009 Feb 21.
[2]Miller LC,Drislane FW.Treatment of status epilepticus.Expert Rev Neurother.2008 Dec;8(12):1817-1827.
[3]Stecker MM,Kramer TH,Raps EC,et al.Treatment of refractory status epilepticus with propofol:clinical and pharmacokinetic findings[J].Epilepsia 1998;39:18-26
[4]Parviainen I,Uusaro A,Kalviainen R,et al.Propofol in the treatment of refractory status epilepticus.Intensive Care Med[J].2006;32(7):1075-1079.
[5]Rossetti AO,Reichhart MD,Schaller MD,et al.Propofol treatment of refractory status epilepticus:A study of 31 episodes[J].Epilepsia 2004;45:757-763.
[6]Jones P J,Wang Y,Smith MD,et al.Hydroxyamide analogs of propofol exhibit state-dependent block of sodium channels in hippocampal neurons:implications for anticonvulsant activity[J].J Pharmacol Exp Ther.2007 Feb;320(2):828-836.
[7]van Gestel JP,Blusse van Oud-Alblas HJ,Malingre M,et al.Propofol and thiopental for refractory status epilepticus in children[J].Neurology 2005;65:591
[8]Vasile B,Rasulo F,Candiani A,et al.The pathophysiology of propofol infusion syndrome:A simple name for a complex syndrome[J].Intens Care Med 2003;29:1417-1425.
[9]Robinson JD,Melman Y,Walsh EP.Cardiac conduction disturbances and ventricular tachycardia after prolonged propofol infusion in an infant.Pacing Clin Electrophysiol.2008 Aug;31(8):1070-1073
[10]Racine R J.Modification of seizure activity by electrical stimulation.Ⅱ.Motor seizure.Electroencephalogr Clin Neurophysiol[J].1972;32(3):281-294.
[11]Feen ES,Bershad EM,Suarez JI.South Med J.Status epilepticus.2008 Apr;101(4):400-406.
[12]Riss J,Cloyd J,Gates J,Collins S.Benzodiazepines in epilepsy:pharmacology and pharmacokinetics.Acta Neurol Scand 2008:118:69-86.
[13]Nowack WJ,Jordan R.Propofol,seizures and generalized paroxysmal fast activity in the EEG.Clin Electroencephalogr.1994 25(3):110-4.
[14]Walder B,Tramer MR,Seeck M.Seizure-like phenomena and propofol:a systematic review.Neurology.2002 May 14;58(9):1327-1332.
[15]Garg R,Dehan M.Convulsions with propofol:A rare adverse event.J Postgrad Med.2009 Jan-Mar;55(1):69-71.
[16]Zeiler SR,Kaplan PW.Propofol withdrawal seizures (or not).Seizure.2008 17(7):665-7.Epub 2008 May 14.
[17]Hickey KS,Martin DF,Chuidian FX.Propofol-induced seizure-like phenomena.J Emerg Med.2005 Nov;29(4):447-9.
[18]Ide A.Case of amoxapine-induced refractory status epilepticus which was successfully treated with propofol.Chudoku Kenkyu.2006 Oct;19(4):407-8.
[19]Arif H,Hirsch Li.Treatment of status epilepticus.Semin Neurol.2008;28(3):342-354.
[20]Leikin JB,Benigno J,Dubow JS,Fisher M.Status epilepticus due to tiagabine ingestion.Am J Ther.2008 May-Jun;15(3):290-291.
[21]Meyer S,Shamdeen MG,Kegel B,et al.Effect of propofol on seizure-like phenomena and electroencephalographic activity in children with epilepsy vs children with learning difficulties.Anaesthesia.2006 Nov;61(11):1040-1047.
[22]Brenner RP.EEG in convulsive and nonconvulsive status epilepticus.J Clin Neurophysiol.2004 Sep-Oct;21(5):319-31.
[23]Kaplan PW.The EEG of status epilepticus.J Clin Neurophysiol.2006 23(3):221-229.
[24]Tang FR,Chen PM,Tang YC,et al.Two-methyl-6-phenylethynyl-pyridine (MPEP),a metabotropic glutamate receptor 5 antagonist,with low doses of MK801 and diazepam:a novel approach for controlling status epilepticus.Neuropharmacology.2007;53(7):821-31.
[25]Walton NY,Treiman DM.Motor and electroencephalographic response of refractory experimental status epilepticus in rats to treatment with MK-801,diazepam,or MK-801 plus diazepam.Brain Res.1991 Jul 5;553(1):97-104.
[26]王恒林,曹江北,王卓强,等。丙泊酚对N-甲基-D-天冬氨酸所致PC12细胞损伤的保护作用。中国药理学与毒理学杂志,2003,17(3):202-203
[27]Ying SW,Goldstein PA.Propofol suppresses synaptic responsiveness of somatosensory relay neurons to excitatory input by potentiating GABAA receptor chloride channels.Mol Pain.2005 Jan 14;1(1):2-12.
[28]Honegger P,Matthieu JM.Selective toxicity of the general anesthetic propofol for GABAergic neurons in rat brain cell cultures[J].J Neurosci Res,1996,45(5):631-636.
[29]Ozt(u｜¨)rk E,Demirbilek S,K(o｜¨)ro(?)lu A,et al.Propofol and erythopoietin antioxidant properties in rat brain injured tissue.Prog Neuropsychopharmacol Biol Psychiatry.2008;32(1):81-86.
[30]Kinirons P,Doherty CP.Status epilepticus:a modern approach to management.Eur J Emerg Med.2008 Aug;15(4):187-195
[1]Rasmussen PA,Yang Y,Rutecki PA.Propofol inhibits epileptiform activity in rat hippocampal slices.Epilepsy Res.1996 Nov;25(3):169-75.
[2]Leander JD,Lawson RR,Ornstein PL,et al.N-methyl-D-aspartic acid-lethality in mice:Selective antagonism by phencyclidine-like drugs.Brain Res,1988,448:115-120
[3]John H,McDonough JR,Shih TM.A study of the N-methyl-D-aspartate antagonistic properties of anticholinergic drugs.Pharmacology Biochemistry and Behavior,1995,51:249-253
[4]Kelsey JE,Sanderson KL,Frye CA.Perforant path stimulation in rats produces seizures,loss of hippocampal neurons,and a deficit in spatial mapping which are reduced by prior MK-801.Behav Brain Res.2000 Jan;107(1-2):59-69.
[5]Lukomskaya NY,Rukoyatkina NI,Gorbunova LV,et al.Studies of the roles of NMDA and AMPA glutamate receptors in the mechanism of corasole convulsions in mice.Neurosci Behav Physiol.2004 Oct;34(8):783-9.
[6]Lukomskaia NIa,Rukoiatkina NI,Gorbunova LV,et al.Role of NMDA and AMPA glutamate receptors in the mechanism of korazol-induced convulsions in mice.Ross Fiziol Zh Im I M Sechenova.2003 Mar;89(3):292-301.
[7]Ohmori H,Sato Y,Namiki A.The anticonvulsant action of propofol on epileptiform activity in rat hippocampal slices.Anesth Analg.2004 Oct;99(4):1095-1101
[8]Feiner JR,Bickler PE,Estrada S,Mild hypothermia,but not propofol,is neuroprotective in organotypic hippocampal cultures.Anesth Analg,2005 Jan;100(1):215-25.
[9]Yamakura T,Sakimura K,Shimoji K,et al.Effects of propofol on various AMPA-,kainate-and NMDA-selective glutamate receptor channels expressed inXenopus oocytes.Neurosci Lett.1995 Mar 31;188(3):187-90.
[10]Orser BA,Bertlik M,Wang LY,et al.Inhibition by propofol (2,6 di-isopropylphenol)of the N-methyl-D-aspartate subtype of glutamate receptor in cultured hippocampal neurones.Br J Pharmacol.1995 Sep;116(2):1761-1768.
[11]Hans P,Bonhomme V,Collette J,et al.Propofol protects cultured rat hippocampal neurons against N-methyl-D-aspartate receptor-mediated glutamate toxicity.J Neurosurg Anesthesiol.1994 Oct;6(4):249-53.
[12]Kingston S,Mao L,Yang L,et al.Propofol inhibits phosphorylation of N-methyl-D-aspartate receptor NRl subunits in neurons.Anesthesiology.2006 Apr;104(4):763-769.
[13]Fibuch EE,Wang JQ.Inhibition of the MAPK/ERK cascade:a potential transcription-dependent mechanism for the amnesic effect of anesthetic propofol.Neurosci Bull.2007 Mar;23(2):l 19-24.
[14]Kozinn J,Mao L,Arora A,et al.Inhibition of glutamatergic activation of extracellular signal-regulated protein kinases in hippocampal neurons by the intravenous anesthetic propofol.Anesthesiology.2006 Dec;105(6):1182-91.
[1].韩济生主编.神经学原理,第二版,北京:北京医科大学出版社,1998:527:1077
[2]Sheng M,Cummings J,Roldan LA,Jan YN,Jan LY.Changing subunit composition of heteromeric NMDA receptors during development of rat cortex.Nature.1994,368:144-147
[3]Monyer H,Burnashev N,Laurie DJ,Sakmann B,Seeburg PH.Developmental and regional expression in the rat brain and functional properties of four NMDA receptors.Neuron 1994,12:529-540.
[4]Al-Ghoul WM,Meeker RB,Greenwood RS.Amygdala kindling alters N-methyl-D-aspartate receptor subunit messenger RNA expression in the rat supraoptic nucleus.Neuroscience.1997,77:985-992.
[5]Mathern GW,Pretorius JK,Mendoza D,Leite JP,Chimelli L,Born DE,Fried I,Assirati JA,Ojemann GA,Adelson PD,Cahan LD,Komblum HI.Hippocampal N-methyl-D-aspartate receptor subunit mRNA levels in temporal lobe epilepsy patients.Ann Neurol.1999,46:343-358.
[6]DeFazio RA,Hablitz JJ.Alterations in NMDA receptors in a rat model of cortical dysplasia.J Neurophysiol.2000,83:315-321.
[7]Ying Z,Bingaman W,Najm IM.Increased numbers of coassembled PSD-95 to NMDA-receptor subunits NR2B and NR1 in human epileptic cortical dysplasia.Epilepsia.2004,45:314-321.
[8]Najm IM,Ying Z,Babb T,et al.Epileptogenocity correlated with increased N-methyl-D-aspartate receptor subunit NR2A/B in human focal cortical dysplasia.Epilepsia 2000;41:971-76
[9]Crino PB,Duhaime AC,Baltuch G,et al.Differential expression of glutamate and GABA-A receptor subunit m-RNA in cortical dysplasia.Neurology 2001;56:906-13
[10]Moddel Q Jacobson B,Ying Z,et al.NMDA receptor NR2B subunit contributes to epileptogenesis in human cortical dysplasia.Brain Res 2005;1046:10-23
[11]Kotani Y,Shimazawa M,Yoshimura S,Iwama T,Hara H.The experimental and clinical pharmacology of propofol,an anesthetic agent with neuroprotective properties.CNS Neurosci Ther.2008;14(2):95-106.
[12]Fibuch EE,Wang JQ.Inhibition of the MAPK/ERK cascade:a potential transcription-dependent mechanism for the amnesic effect of anesthetic propofol.Neurosci Bull.2007 Mar;23(2):l 19-24.
[13]Kozinn J,Mao L,Arora A,Yang L,Fibuch EE,Wang JQ.Inhibition of glutamatergic activation of extracellular signal-regulated protein kinases in hippocampal neurons by the intravenous anesthetic propofol.Anesthesiology,2006 Dec;105(6):l 182-1191.
[14]Racine R J.Modification of seizure activity by electrical stimulation.Ⅱ.Motor seizure.Electroencephalogr Clin Neurophysiol[J].1972;32(3):281-294.
[15]Sheng M,Cummings J,Roldan LA,Jan YN,Jan LY.Changing subunit composition of heteromeric NMDA receptors during development of rat cortex.Nature.1994,368:144-147
[16]Monyer H,Burnashev N,Laurie DJ,Sakmann B,Seeburg PH.Developmental and regional expression in the rat brain and functional properties of four NMDA receptors.Neuron 1994,12:529-540.
[17]Chen Q,He S,Hu XL,et al.Differential roles of NR2A- and NR2B-containing NMDA receptors in activity-dependent brain-derived neurotrophic factor gene regulation and limbic epileptogenesis.J Neurosci.2007 Jan 17;27(3):542-552.
[18]Huo JZ,Dykstra CM,Gurd JW.Neurosci Lett.Increase in tyrosine phosphorylation of the NMDA receptor following the induction of status epilepticus.2006 Jul 3;401(3):266-270.
[19]Yang J,Woodhall GL,Jones RS.Tonic facilitation of glutamate release by presynaptic NR2B-containing NMDA receptors is increased in the entorhinal cortex of chonically epileptic rats.J Neurosci.2006;26(2):406-410.
[20]Borb(?)ly S,Dob(?)E,Cz(?)g(?) D,et al.Modification of ionotropic glutamate receptor-mediated processes in the rat hippocampus following repeated,brief seizures.Neuroscience.2009 Mar 3;159(1):358-368.
[21]王恒林,曹江北,王卓强,等。丙泊酚对N-甲基-D-天冬氨酸所致PC12细胞损伤的保护作用。中国药理学与毒理学杂志,2003,17(3):202-203
[22]Grasshoff C,Gillessen T.Effects of propofol on N-methyl-D-aspartate receptor-mediated calcium increase in cultured rat cerebrocortical neurons.Eur J Anaesthesiol.2005 Jun;22(6):467-470
[23]Fibuch EE,Wang JQ.Inhibition of the MAPK/ERK cascade:a potential transcription-dependent mechanism for the amnesic effect of anesthetic propofol.Neurosci Bull.2007 Mar;23(2):119-124.
[24]Kingston S,Mao L,Yang L,et al.Propofol inhibits phosphorylation of N-methyl-D-aspartate receptor NRl subunits in neurons.Anesthesiology.2006;104(4):763-769.
[1]Gibbs JW,Shumate MD,Coulter DA.Differential epilepsy-associated alterations in postsynaptic GABAA receptor function in dentate granule and CAl neurons.J Neurophysiol 1997;77:1924-1938.
[2]Mangan PS,Bertram EH.Shortened-duration GABA(A) receptor-mediated synaptic potentials underlie enhanced CAl excitability in a chonic model of temporal lobe epilepsy.Neuroscience 1997;80:1101-1111.
[3]Galanopoulou AS.Developmental patterns in the regulation of chloride homeostasis and GABA(A) receptor signaling by seizures.Epilepsia.2007;48Suppl 5:14-8.
[4]Volk HA,Arabadzisz D,Fritschy JM,et al.Neurobiol Dis.Antiepileptic drug-resistant rats differ from drug-responsive rats in hippocampal neurodegeneration and GABA(A) receptor ligand binding in a model of temporal lobe epilepsy.2006;21(3):633-46.
[5]Martella G,De Persis C,Bonsi P,et al.Inhibition of persistent sodium current fraction and voltage-gated L-type calcium current by propofol in cortical neurons:implications for its antiepileptic activity.Epilepsia.2005;46(5):624-35.
[6]Gilby KL,Da Silva AG,McIntyre DC.Differential GABA(A) subunit expression following status epilepticus in seizure-prone and seizure-resistant rats:a putative mechanism for refractory drug response.Epilepsia.2005;46 Suppl 5:3-9.
[7]Raol YH,Lund IV,Bandyopadhyay S,et al.Enhancing GABA(A) receptor alpha 1 subunit levels in hippocampal dentate gyrus inhibits epilepsy development in an animal model of temporal lobe epilepsy.J Neurosci.2006;26(44):11342-11346.
[8]Bethmann K,Fritschy JM,Brandt C,L(o｜¨)scher W.Antiepileptic drug resistant rats differ from drug responsive rats in GABA A receptor subunit expression in a model of temporal lobe epilepsy.Neurobiol Dis.2008 Aug;31(2):169-87.
[9]Orser BA,Canning K J,Macdonald JF.Mechanisms of general anesthesia.Curr Opin Anaesthesiol.2002 Aug;15(4):427-33.
[10]Sebel LE,Richardson JE,Singh SP,Bell SV,Jenkins A.Additive effects of sevoflurane and propofol on gamma-aminobutyric acid receptor function.Anesthesiology.2006 Jun;104(6):1176-83.
[11]Rasmussen PA,Yang Y,Rutecki PA.Propofol inhibits epileptiform activity in rat hippocampal slices.Epilepsy Res.1996 Nov;25(3):169-75.
[12]王恒林,米卫东,赵从,等。丙泊酚对毒鼠强诱发大鼠SE的抑制作用及其皮层GABA受体α1亚单位表达的影响,军医进修学院学报,2009;
[13]Feng H J,Macdonald RL.Multiple actions of propofol on alphabetagamma and alphabetadelta GABAA receptors.Mol Pharmacol.2004Dec;66(6):1517-24.
[14]Lam DW,Reynolds JN.Modulatory and direct effects of propofol on recombinant GABAA receptors expressed in xenopus oocytes:influence of alpha- and gamma2-subunits.Brain Res.1998 Feb 16;784(1-2):179-87.
[15]Uchida I,Li L,Yang J.The role of the GABA(A) receptor alphal subunit N-terminal extracellular domain in propofol potentiation of chloride current.Neuropharmacology.1997 Nov-Dec;36(11-12):1611-21.
[1]Costa M.S.Rocha J.B.Perosa S.R.Cavalheiro E.A.Naffah-Mazzacoratti M.G.Pilocarpine-induced status epilepticus increases glutamate release in rat hippocampal synaptosomes,Neurosci.Lett.2004,356:41-44.
[2]Tejada S,Roca C,Sureda A,et al.Antioxidant response analysis in the brain after pilocarpine treatments.Brain Res Bull.2006 May 15;69(5):587-592.
[3]Chuang YC,Chen SD,Lin TK,et al.Upregulation of nitric oxide synthase Ⅱcontributes to apoptotic cell death in the hippocampal CA3 subfield via a cytochome c/caspase-3 signaling cascade following induction of experimental temporal lobe status epilepticus in the rat.Neuropharmacology.2007Apr;52(5):1263-73.
[4]Liang LP,Patel M.Seizure-induced changes in mitochondrial redox status.Free Radic Biol Med.2006 Jan 15;40(2):316-22.
[5]Kovács R,Schuchmann S,Gabriel S,et al.Free radical-mediated cell damage after experimental status epilepticus in hippocampal slice cultures.J Neurophysiol.2002 Dec;88(6):2909-18.
[6]Kobayashi K,Yoshino F,Takahashi SS,Direct assessments of the antioxidant effects of propofol medium chain triglyceride/long chain triglyceride on the brain of stroke-prone spontaneously hypertensive rats using electron spin resonance spectroscopy.Anesthesiology.2008 Sep;109(3):426-35.
[7]Ozt(u｜¨)rk E,Demirbilek S,K(O｜¨)ro(g｜ˇ)lu A,Propofol and erythopoietin antioxidant properties in rat brain injured tissue.Prog Neuropsychopharmacol Biol Psychiatry.2008 Jan 1;32(1):81-6
[8]Daskalopoulos R,Korcok J,Tao L,Accumulation of intracellular ascorbate from dehydroascorbic acid by astrocytes is decreased after oxidative stress and restored by propofol.Glia.2002 Aug;39(2):124-32.
[9]Bayona NA,Gelb AW,Jiang Z,et al.Propofol neuroprotection in cerebral ischemia and its effects on low-molecular-weight antioxidants and skilled motor tasks.Anesthesiology.2004 May;100(5):1151-9.
[10]Lee Y,Chung C,Oh YS.Effectiveness of propofol pretreatment on the extent of deranged cerebral mitochondrial oxidative enzyme system after incomplete forebrain ischemia/reperfusion in rats.J Korean Med Sci.2000 Dec;15(6):627-30.
[11]Young Y,Menon DK,Tisavipat N,et al.Propofol neuroprotection in a rat model of ischaemia reperfusion injury.Eur J Anaesthesiol.1997 May;14(3):320-6.
[12]Racine R J.Modification of seizure activity by electrical stimulation.Ⅱ.Motor seizure.Electroencephalogr ClinNeurophysiol[J].1972;32(3):281-294.
[13]Westman N,Marklund S.L.Copper and zinc containing superoxide dismutase and manganese containing superoxide dismutase in human tissues and human malignant tumors,1982,Cancer Res 41:2962-2966.
[14]Freitas,S.M.Vasconcelos,F.C.Souza,G.S.et al.Oxidative stress in the hippocampus after pilocarpine-induced status epilepticus in Wistar rats,FEBS J.2005,272,1307-1312.
[15]Yu X,Shao XG,Sun H,Activation of cerebral peroxisome proliferator-activated receptors gamma exerts neuroprotection by inhibiting oxidative stress following pilocarpine-induced status epilepticus.Brain Res.2008 Mar 20;1200:146-58.
[16]Tejada S,Sureda A,Roca C,Gamundi A,Esteban S.Antioxidant response and oxidative damage in brain cortex after high dose of pilocarpine.Brain Res Bull.2007 Jan 9;71(4):372-5.
[17]Rajasekaran K.Seizure-induced oxidative stress in rat brain regions:blockade by nNOS inhibition.Pharmacol Biochem Behav.2005 Feb;80(2):263-72.
[18]Sleven HJ,Gibbs JE,Cock H.The antioxidant N-acetyl-L-cysteine does not prevent hippocampal glutathione loss or mitochondrial dysfunction associated with status epilepticus.Epilepsy Res.2006 May;69(2):165-9.
[19]Anderson MF,Nilsson M,Sims NR.Glutathione monoethylester prevents mitochondrial glutathione depletion during focal cerebral ischemia.Neurochem Int.2004 Feb;44(3):153-9.
[20]Riischenschmidt C,Chen J,Becker A,Riazanski V,Beck H.Functional properties and oxidative modulation of A-type K currents in hippocampal granule cells of control and chonically epileptic rats.Eur J Neurosci.2006 Feb;23(3):675-85.
[21]Sleven H,Gibbs JE,Heales S,Thorn M,Cock H.Depletion of reduced glutathione precedes inactivation of mitochondrial enzymes following limbic status epilepticus in the rat hippocampus.Neurochem Int.2006 Jan;48(2):75-82.
[22]Klaidman LK,Adams JD Jr,Cross R,Pazdernik TL,Samson F.Alterations in brain glutathione homeostasis induced by the nerve gas soman.Neurotox Res.2003;5(3):177-82.
[23]George B,Kulkarni SK.Dopaminergic modulation of lithium/pilocarpineinduced status epilepticus in rats.Methods Find Exp Clin Pharmacol.1997Sep;19(7):481-8.
[24]Dal-Pizzol F,Klamt F,Vianna MM,Schoder N,Quevedo J,Benfato MS,Moreira JC,Walz R.Lipid peroxidation in hippocampus early and late after status epilepticus induced by pilocarpine or kainic acid in Wistar rats.Neurosci Lett.2000 Sep 22;291(3):179-82.
[25]Liu ZW,Zhang T,Yang Z.Involvement of nitric oxide in spatial memory deficits in status epilepticus rats.Neurochem Res.2007 Nov;32(l l):1875-83.
[26]Gupta YK,Briyal S.Protective effect of vineatrol against kainic acid induced seizures,oxidative stress and on the expression of heat shock proteins in rats.Eur Neuropsychopharmacol.2006 Feb;16(2):85-91.
[27]Santos LF,Freitas RL,Xavier SM,Saldanha GB,Freitas RM.Neuroprotective actions of vitamin C related to decreased lipid peroxidation and increased catalase activity in adult rats after pilocarpine-induced seizures.Pharmacol Biochem Behav.2008;89(1):1-5.
[28]Kobayashi K,Yoshino F,Takahashi SS,Todoki K,Maehata Y,Komatsu T,Yoshida K,Lee MC.Direct assessments of the antioxidant effects of propofol medium chain triglyceride/long chain triglyceride on the brain of stroke-prone spontaneously hypertensive rats using electron spin resonance spectroscopy.Anesthesiology.2008;109(3):426-435.
[29]Vansant G,Trauger RJ,Cameron A,Vendemelio M,Kreitschitz S,Carlo AT,Banaszczyk MG,Carlo DJ,Hendler S.Propofol hemisuccinate suppression of experimental autoimmune encephalomyelitis.Autoimmunity.2007;40(3):180-186.
[30]Acquaviva R,Campisi A,Murabito P,Raciti G,Avola R,Mangiameli S,Musumeci I,Barcellona ML,Vanella A,Li Volti G.Propofol attenuates peroxynitrite-mediated DNA damage and apoptosis in cultured astrocytes:an alternative protective mechanism.Anesthesiology.2004;101 (6):1363-1371.
[31]Bayona NA,Gelb AW,Jiang Z,Wilson JX,Urquhart BL,Cechetto DF.Propofol neuroprotection in cerebral ischemia and its effects on low-molecular-weight antioxidants and skilled motor tasks.Anesthesiology.2004;100(5):1151-9.
[32]Lee Y,Chung C,Oh YS.Effectiveness of propofol pretreatment on the extent of deranged cerebral mitochondrial oxidative enzyme system after incomplete forebrain ischemia/reperfusion in rats.J Korean Med Sci.2000;15(6):627-630.
[33]Ozturk E,Demirbilek S,Kadir But A,Saricicek V,Gulec M,Akyol O,Ozcan Ersoy M.Antioxidant properties of propofol and erythopoietin after closed head injury in rats.Prog Neuropsychopharmacol Biol Psychiatry.2005 Jul;29(6):922-7.
[34]Ozturk E,Demirbilek S,Koroglu A,But A,Begec ZO,Gulec M,Akyol O,Ersoy MO.Propofol and erythopoietin antioxidant properties in rat brain injured tissue.Prog Neuropsychopharmacol Biol Psychiatry.2008 Jan 1;32(1):81-86.
[35]Ceylan BG,Yilmaz F,Eroglu F,Yavuz L,Gulmen S,Vural H.Oxidant and antioxidant activities of different anesthetic techniques.Propofol versus desflurane.Saudi Med J.2009 Mar;30(3):371-6.
[36]Cinnella G,Vendemiale G,Dambrosio M,Serviddio G,Pugliese PL,Aspromonte G,Altomare E.Effect of Propofol,Sevoflurane and Desflurane on systemic redox balance.Int J Immunopathol Pharmacol.2007;20(3):585-93.
[37]Peterson SL,Purvis RS,Griffith JW.Comparison of neuroprotective effects induced by alpha-phenyl-N-tert-butyl nitrone(PBN) and N-tert-butyl-alpha-(2sulfophenyl) nitrone(S-PBN) in lithium-pilocarpine status epilepticus.Neurotoxicology.2005 Dec;26(6):969-79.
[1]Epilepsy Foundation of America.Treatment of convulsive status epilepticus:recommendations of the Epilepsy Foundation of America's Working Group on Status Epilepticus.JAMA 1993;270:854-859
[2]Lowenstein DH,Alldredge BK.Status epilepticus.N Engl J Med 1998;338:970-976
[3]Chapman MG,Smith M,Hirsch NP.Status epilepticus[J].Anaesthesia 2001;56:648-659
[4]Lowenstein DH,Bleck T,Macdonald RL.It's time to revise the definition of status epilepticus[J].Epilepsia 1999;40:120-122
[5]Prasad A,Worrall BB.Bertram EH,et al.Propofol and midazolam in the treatment of refractory status epilepticus[J].Epilepsia 2001;42:380-386
[6]Bleck TP.Management approaches to prolonged seizures and status epilepticus[J].Epilepsia 1999;40(suppl):S59-S63
[7]Mayer SA,Claassen J,Lokin J,et al.Refractory status epilepticus:frequency,risk factors,and impact on outcome[J].Arch Neurol,2002,59(2):205-210
[9]Garzon E,Fernandez RM,Sakamoto AC.Analysis of clinical characteristics and risk factors for mortality in human status epilepticus[J].Seizure 2003;12:337-345.
[10]Stecker MM,Kramer TH,Raps EC,et al.Treatment of refractory status epilepticus with propofol:clinical and pharmacokinetic findings[J].Epilepsia 1998;39:18-26
[11]Parviainen I,Uusaro A,Kalviainen R,et al.Propofol in the treatment of refractory status epilepticus.Intensive Care Med.2006;32(7):1075-1079.
[12]Rossetti AO,Reichhart MD,Schaller MD,et al.Propofol treatment of refractory status epilepticus:A study of 31 episodes[J].Epilepsia 2005;45:757-763.
[13]Jones P J,Wang Y,Smith MD,et al.Hydroxyamide analogs of propofol exhibit state-dependent block of sodium channels in hippocampal neurons:implications for anticonvulsant activity[J].J Pharmacol Exp Ther.2007Feb;320(2):828-836.
[14]付秀全,吴宏涛.丙泊酚和硫喷妥钠治疗难治性SE18例疗效观察.实用临床医院杂志,2005,4(2):55-56
[15]朱育昌,许志恩.不同药物治疗难治性全面性SE的疗效分析.吉林医学,2005,26(8):837-838
[16]van Gestel JP,Blusse van Oud-Alblas H J,Malingre M,et al.Propofol and thiopental for refractory status epilepticus in children.Neurology 2005;65:591-592.
[17]周力文,赵贺堂,张世杰.丙泊酚持续静滴治疗小儿SE的临床观察.中国实用儿科杂志,2005,3(20):173-174
[18]Naylor DE,Liu H,Wasterlain CG.Trafficking of GABA(A) receptors,loss of inhibition,and a mechanism for pharmacoresistance in status epilepticus[J].J Neurosci.2005 Aug 24;25(34):7724-7733.
[19]Ying SW,Goldstein PA.Propofol suppresses synaptic responsiveness of somatosensory relay neurons to excitatory input by potentiating GABAA receptor chloride channels[J].Mol Pain.2005;14;1(1):2-12.
[20]Smith I,White PF,Nathanson M,et al.Propofol:an update on its clinical use.Anesthesiology 1994;81:1005-1043
[21]Hara M,Kai Y,Ikemoto Y.Propofol activates GABAA receptor-chloride ionophore complex in dissociated hippocampal pyramidal neurons of the rat.Anesthesiology 1993;79:781-788
[22]Fujikawa DG.Prolonged seizures and cellular injury:Understanding the connections[J].Epilepsy Behav 2005;7:S3-11
[23]Rice AC,DeLorenzo RJ.NMDA receptor activation during status epilepticus is required for the development of epilepsy.Brain Res 1998;782:240-247
[24]Pal S,Sombati S,Limbrick DD Jr,et al.In vitro status epilepticus causes sustained elevation of intracellular calcium levels in hippocampal neurons[J].Brain Res 1999;851:20-31
[25]Murthy JMK.Refractory status epilepticus[J].Neurol India 2006;54:354-358
[26]王恒林,曹江北,王卓强,等.丙泊酚对N-甲基-D-天冬氨酸所致PC12细胞损伤的保护作用.中国药理学与毒理学杂志2003;17(3):202-205
[27]Agrawal N,Alonso A,Ragsdale DS.Increased persistent sodium currents in rat entorhinal cortex layer V neurons in a post-status epilepticus model of temporal lobe epilepsy.Epilepsia 2003;44:1601-1604
[28]Martella G,De Persis C,Bonsi P,et al.Inhibition of persistent sodium current fraction and voltage-gated L-type calcium current by propofol in cortical neurons:implications for its anti-epileptic activity.Epilepsia 2005;46:624-635.
[29]Vasile B,Rasulo F,Candiani A,et al.The pathophysiology of propofol infusion syndrome:A simple name for a complex syndrome.Intens Care Med 2003;29:1417-1425.
[30]Marik PE.Propofol:therapeutic indications and side-effects.Curr Pharm Des 2004;10:3639-3649.
[31]Sabsovich I,Rehman Z,Yunen J,Propofol infusion syndrome:a case of increasing morbidity with traumatic brain injury.Am J Crit Care.2007Jan;16(1):82-85.
[32]Vasile B,Rasulo F,Candiani A,et al.The pathophysiology of propofol infusion syndrome:a simple name for a complex syndrome.Intensive Care Med 2003;29:1417-1425
[33]Kang TM.Propofol infusion syndrome in critically ill patients.Ann Pharmacother 2002;36:1453-1456
[34]McKeage K,Perry CM.Propofol:a review of its use in intensive care sedation of adults.CNS Drugs 2003;17:235-272
[35]Short TG,Young Y Toxicity of intravenous anaesthetics.Best Pract Res Clin Anaesthesiol 2003;17:77-89
[36]Cornfield DN,Tegtmeyer K,Nelson MD,Milla CE,Sweeney M.Continuous profol infusion in 142 critically ill children.Pediatrics 2002;110:1177-1181.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |