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运动训练强度及电刺激对脑卒中恢复机制和功能影响的研究
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摘要
第一部分不同强度跑台训练对脑缺血大鼠NR2B受体表达的影响
     目的:采用脑缺血模型研究不同强度跑台训练对脑卒中大鼠NR2B受体表达量的影响,为临床脑卒中康复中选择合适的运动强度提供理论依据。
     方法:144只雄性成年SD大鼠随机分至4个组,即假手术组、静止组、低强度训练组、中强度训练组,每组36只。108只大鼠接受永久性MCAO模型,造模24小时后,给予不同强度的跑台训练干预。在手术后第3天、第7天、第14天进行神经功能学评分、体重测定,之后断头取材,分别进行磷酸化NR2B受体表达量的检测、脑含水量和脑梗死体积测定。
     结果:与静止组相比,运动训练组脑缺血大鼠海马组织中磷酸化NR2B受体的表达量随着时间延长明显降低。在脑缺血后第3天和第7天,低强度训练组的大鼠海马中该受体的表达量明显低于中强度训练组(P<0.05),第14天时这两组该受体的表达量没有显著性差异。TTC染色结果显示,第7天、第14天运动训练组脑梗死体积与静止组相比明显减少(P<0.01),并且低强度训练组的脑梗死体积也明显小于中等强度训练组(P<0.05)。运动训练组与静止组相比可以明显减轻神经功能缺损程度(p<0.05),但直到第14天时才观察到明显的统计学差异,且低强度训练组减轻神经功能缺损的程度优于中等强度训练组。脑组织水肿程度的结果显示:低强度训练组可以明显减轻脑水肿的程度(p<0.05),但是中强度训练组并不能减轻脑水肿程度。从实验过程中动物死亡情况来看,低强度训练可以明显降低脑梗后的死亡率,而中强度训练则不能明显降低死亡率。大鼠的体重变化结果显示:与静止组相比,低强度训练可以明显促进体重的恢复,而中等强度训练则效果不明显。
     结论:脑缺血后进行运动训练是有效的而且必要的。同时低强度运动训练在降低磷酸化NR2B受体的表达量,减小脑梗死体积,促进脑水肿吸收,降低脑缺血后死亡率等方面,是更加有效的干预手段。这提示在临床实践中,早期给予脑缺血后患者给予低强度的运动训练可能更安全、更有效。
     第二部分信号式功能性电刺激对脑卒中偏瘫患者上肢运动功能、认知功能和情绪的影响
     目的:探讨信号式功能性电刺激对脑卒中患者早期上肢运动功能、认知功能和情绪的影响。
     方法:48例脑卒中患者随机分为4组,即信号式功能性电刺激治疗组(简称信号组)、传统低频电刺激治疗组(简称低频组)、肌电反馈电刺激治疗组(简称肌电组)以及无电刺激治疗组。入组后,所有患者给予常规康复治疗,包括内科常规药物治疗和相同的基础康复治疗。此外,各电刺激组患者予以相应的电刺激治疗。分别在治疗前、治疗后20天时采用简化Fugl-Meyer运动功能评定(上肢部分)、功能综合评定量表(FCA)、简易精神量表(MMSE)和汉密尔顿抑郁量表(HAMD)对患者进行上肢运动功能、认知功能和情绪的评定并统计分析。
     结果:治疗前各组各项量表评分在统计学上均未见显著性差异(P>0.05)。治疗后20天时,各组上肢运动功能都有不同程度恢复,但肌电组、低频组、信号组与治疗前比较差异均具有统计学意义(P<0.05);无电刺激治疗组与治疗前比较差异不显著(P>0.05)。治疗20天后,肌电组、信号组简化Fugl-Meyer运动功能评定(上肢部分)和功能综合评定量表评分与无电刺激组、低频组比较均有显著性差异(P<0.05),但信号组与肌电组相比,差异无统计学意义(P>0.05)。经过20天的治疗,各组的认知功能也有不同程度恢复。其中,信号式功能性电刺激组、肌电反馈电刺激组的MMSE和FCA认知部分的评分与治疗前比较均有显著性差异(P<0.05);国产低频电刺激组和无电刺激治疗组的MMSE以及FCA认知部分的评分治疗前、后比较差异不显著(P>0.05)。治疗20天后,信号功能电刺激组与肌电反馈电刺激组比较,认知部分的功能评定差异均无统计学意义(P>0.05);但两者与无电刺激组和国产低频电刺激组比较则有统计学意义(P<0.05);国产低频电刺激组与无电刺激组比较,MMSE和FCA认知部分的评定量表结果没有显著性差异(P>0.05)。经过治疗后,信号组和肌电组的患者,抑郁情绪得到很好的改善,国产低频组和无电刺激组患者的抑郁情绪改善不明显。
     结论:信号式功能性电刺激治疗可促进脑卒中患者受损的运动功能恢复,改善情绪障碍,提高患者认知功能,其恢复程度近似于肌电生物反馈组,但高于国产低频电刺激组和无电刺激组。
PartⅠThe effects of different treadmill training intensity on the expression of NR2B receptor in the cerebral ischemic rats
     Objectives:To study the effect of different training intensity on the expression of NR2B receptor in rats with cerebral ischemia by the MCAO model and provide a theoretical basis to the selection of the appropriate exercise intensity for clinical rehabilitation.
     Methods:Adult SD rats were randomly divided into 4 groups, namely no exercise group (NE group), low intensity training group (LIT group, v=15m/min), moderate intensity training group (MIT group, v=20m/min) and sham group. On the 3rd day, the 7th day and the 14th day after the operation, the brains were subjected to detect the expression of the phospho-NR2B (p-NR2B) receptor, one kind of subunits of N-methyl-D-aspartate receptor (NMDA receptor). Addition, neurological deficit score (NDS), body weight, cerebral infarction volume and extent of brain edema were examined to evaluate the safety and the effect of exercise on the acute ischemic rat.
     Results:Treatment with exercise significantly decreased the expression of the p-NR2B receptor compared with rats in the NE group at the 3rd day, the 7th day and the 14th day after MCAO. At every sampling time point, the expression of the p-NR2B receptor in LIT group was much lower than the MIT group except the 14th day. The TTC staining showed that compared with the NE group, exercise training could significantly decrease the cerebral infarction volume on the 7th day and the 14th day (P<0.01). The cerebral infarction volume of the LIT group was significantly smaller than the MIT group. Exercise training significantly reduced the degree of neurological deficits (p<0.05), but until the 14th day the differences were not stastically. Meantime, the reduced degree of neurological deficit in LIT group was greater than that in MIT group. From the results of the dry and wet brain tissue:the LIT group could significantly reduce the extent of brain edema(P<0.05), but the MIT group did not reduce it. Similarly, from the death record, the LIT might reduce the mortality after cerebral ischemia, while the MIT had no effect like this. Body weight change in rats showed that:compared with the NE group, the LIT could significantly promote the recovery of body weight, while the MIT was ineffective.
     Conclusion:Exercise training after cerebral ischemia is useful and necessary. LIT is more effective intervention means in reducing the expression of the phosphorylation of NR2B receptor, reducing infarct volume, promoting brain edema absorption and reducing mortality after cerebral ischemia. In the clinical practice, cerebral ischemia treated with low intensity exercise training may be more secure and effective.
     Part II Effects of Instructional Functional Electrical Stimulation on the Upper Extremity Motor Function and the cognitive deficit in Patients with Stroke
     Objectives:To explore the effects of instructional functional electrical stimulation (IFES) on the upper extremity motor function and the cognitive deficit in patients with stroke.
     Methods:Forty-eight patients after stroke were randomly divided into four groups as follow:the IFES group, the traditional electrical stimulation (TES) group, the electromyogram-triggered neuromuscular stimulation (ETNS) group and the no electrical stimulation group. All the subjects received the same rehabilitation training and internal medicine treatment. Besides, patients in IFES, TES and ETNS groups were given a 20 days program of electrical stimulation to the extensor muscles of wrist(20 minutes, once a day) via surface electrodes. All subjects were assessed with the simplified Fugl-Meyer scores (the upper extremity part), the functional comprehensive assessment (FCA), the mini-mental state examination (MMSE) and the Hamilton depression rating scale (HAMD) before treatment and on the 20th day after treatment.
     Results:No significant differences were found in every rating scale among the groups at the recruitment. After 20-day treatment, every group made progress in some extent, especially in the IFES group, the ETNS group and the TES group (p<0.05) On the 20th day, compared with the no stimulation group and the TES group, there were significant differences in the upper extremity Fugl-Meyer scores and the FCA scores of the IFES group and the ETNS group (p<0.05), but no statistic differences can be found between these two groups (P>0.05). After 20-day's treatment, every group made progress in cognitive function more or less, especially in the IFES group and the ETNS group (p<0.05). On the 20th day, no significant differences in all the cognitive scales were found between the IFES group and the ETNS group. However, compared with the TES group and the no stimulation group there were note differences in MMSE and the cognitive part of the FCA scales (p<0.05). What's more, there were no differences between the TES group and the no stimulation group in all the cognitive scales. After treatment, the patients had an obvious decreasing in depression degree in the IFES group and the ETNS group.
     Conclusion:The study indicated that IFES could enhance the upper extremity motor function, improve the functional dependence and decrease the cognitive function defict and the degree of depression in patients with stroke. Its therapeutic efficacy was similar to the ETNS group but better than the TES group and the no electrical stimulation group.
引文
[1]Lopez AD, Mathers CD, Ezzati M, et al. Global and regional burden of disease and risk factors,2001:systematic analysis of population health data [J]. Lancet,2006, 367(9524):1747-1757.
    [2]Marin R, Williams A, Hale S, et al. The effect of voluntary exercise exposure on histological and neurobehavioral outcomes after ischemic brain injury in the rat [J]. Physiol Behav,2003,80 (2-3):167-175.
    [3]Yang YR, Wang RY, Wang PS, et al. Treadmill training effects on neurological outcome after middle cerebral artery occlusion in rats [J]. Can J Neurol Sci,2003,30 (3):252-258.
    [4]Nudo RJ, Wise BM, SiFuentes F, et al. Neural substrates for the effects of rehabilitative training on motor recovery after ischemic infarct [J]. Science,1996,272 (5296):1791-1794.
    [5]Dombovy ML, Sandok BA, Basford JR. Rehabilitation for stroke:a review [J]. Stroke,1986,17 (3):363-369.
    [6]Park JW, Bang MS, Kwon BS, et al. Early treadmill training promotes motor function after hemorrhagic stroke in rats [J]. Neurosci Lett,2010,471(2):104-108.
    [7]Toby BC, Amanda GT, Janice MC, et al. Very Early Mobilization After Stroke Fast-Tracks Return to Walking. Further Results From the Phase Ⅱ AVERT Randomized Controlled Trial [J]. Stroke,2011,42(1):153-158.
    [8]Yang YR, Wang RY, Wang PS. Early and late treadmill training after focal brain ischemia in rats [J]. Neurosci Lett,2003,339(2):91-94.
    [9]Matsuda F, Sakakima H, Yoshida Y. The effects of early exercise on brain damage and recovery after focal cerebral infarction in rats [J]. Acta Physiol (Oxf), 2011,201(2):275-278.
    [10]郑庆平,胡永善,白玉龙,等.局灶性脑缺血大鼠康复训练干预时间的研究[J].复旦学报,2007,34(6):895-898.
    [11]Cramer SC. The VECTORS study when too much of a good thing is harmful. Neurology.2009,73 (3):170-171.
    [12]Dromerick AW, Lang CE, Birkenmeier RL, et al. Very Early Constraint-Induced Movement during Stroke Rehabilitation (VECTORS) A single-center RCT [J]. Neurology,2009,73 (3):195-201.
    [13]Chen M, Lu TJ. Differential roles of NMD A receptor subtypes in ischemic neuronal cell death and ischemic tolerance [J]. Stroke,2008,39 (11):3042-3048.
    [14]Lo EH, Dalkara T, Moskowitz MA. Mechanisms, challenges and opportunities in stroke [J]. Nat Rev Neurosci,2003,4 (5):399-415.
    [15]Hardingham GE, Fukunaga Y, Bading H. Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways [J]. Nat Neurosci,2002,5 (5):405-414.
    [16]Barbara P, Anna T, Ilaria B, et al. NR2B Subunit Exerts a Critical Role in Postischemic Synaptic Plasticity [J]. Stroke,2006,37(7):1895-1901.
    [17]Liu TP, Wong M, Aarts A, et al. NMDA receptor subunits have differential roles in mediating excitotoxic neuronal death both in vitro and in vivo [J]. Journal of Neuroscience,2007,27(11):2846-2857.
    [18]Chenard BL, Menniti FS. Antagonists selective for NMDA receptors containing the NR2B subunit [J]. Current Pharmaceutical Design,1999,5(5):381-404.
    [19]Saltarelli M, Weaver J, Hsu C, et al. Randomized double-blind, placebo-controlled study to evaluate the safety and efficacy of CP-101606 (traxoprodil), an NR2B-selective N-methyl-d-aspartate antagonist in subjects with acute ischemic stroke [J]. Stroke,2004,35(1):241-245.
    [20]Jia J, Hu YS, Wu Y, et al. Treadmill pre-training suppresses the release of glutamate resulting from cerebral ischemia in rats [J]. Exp Brain Res,2010, 204(2):173-179.
    [21]Zhang F, Jia J, Wu Y, et al. The Effect of Treadmill Training Pre-Exercise on Glutamate Receptor Expression in Rats after Cerebral Ischemia Int [J]. J Mol Sci, 2010,11(7):2658-2669.
    [22]Glanz M, Klawansky S, Stason W, et al. Functional electrostimulation in poststroke rehabilitation:a meta-analysis of the randomized controlled trials [J]. Arch Phys Med Rehabil,1996,77(6):549-553.
    [23]Popovic MR, Curt a, Keller T, et al. Functional electrical stimulation for grasping and walking:indications and limitation [J]. Spinal Cord,2001,39 (8): 403-412.
    [24]Kimberley TJ, Lewis SM, Auerbach EJ, et al. Electrical stimulation driving functional improvements and cortical changes in subjects with stroke [J]. Exp Brain Res,2004,154(4):450-460.
    [25]Smith GV, Alon G, Roys GT, et al. Functional MRI determination of a dose-response relationship to lower extremity neuromuscular electrical stimulation in healthy subjects [J]. Exp Brain Res,2003,150(1):33-39.
    [26]Burnett MG, Shimazu T, Szabados T, et al. Electrical forepaw stimulation during reversible forebrain ischemia decreases infarct volume [J]. Stroke,2006,37(5): 1327-1331.
    [27]Tamura A, Gotoh O, Sano K, et al. Focal cerebral infarction in the rat:II. Neuropathological study and local cerebral blood flow pattern [J]. No To Shinkei, 1986,38(9):859-863.
    [28]Longa EZ, Weinstein PR, Carlson S, et al. Reversible middle cerebral artery occlusion without craniectomy in rats [J]. Stroke,1989,20(1):84-91.
    [29]Brooks GA, White TP. Determination of metabolic and heart rate responses of rats to treadmill exercise [J]. J Appl Physiol,1978,45(6):1009-1015.
    [30]Soya H, Nakamura T, Deocaris CC, et al. BDNF induction with mild exercise in the rat hippocampus [J]. Biochem Biophysi Res Comm,2007,358(4):961-967.
    [31]Loftis JM, Janowsky A. The N-methyl-D-aspartate receptor subunit NR2B: localization, functional properties, regulation, and clinical implications [J]. Pharmacol Ther,2003,97(1):55-85.
    [32]French B, Thomas LH, Leathley MJ, et al. Repetitive task training for improving functional ability after stroke [J]. Cochrane Database Syst Rev,2007,4: CD006073.
    [33]Myint JMW, Yuen GFC, Yu TKK, et al. A study of constraint-induced movement therapy in subacute stroke patients in Hong Kong [J]. Clin Rehabil,2008, 22(2):112-124.
    [34]Auer RN. Non-pharmacologic (physiologic) neuroprotection in the treatment of brain ischemia [J]. Ann N Y Acad Sci,2001,939():271-282.
    [35]Ide K, Horn A, Secher NH. Cerebral metabolic response to submaximal exercise [J]. J Appl Physiol,1999,87(5):1604-1608.
    [36]van Praag H, Kempermann G, Gage FH. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus [J]. Nat Neurosci,1999,2(3): 266-270.
    [37]Kleim JA, Cooper NR, VandenBerg PM. Exercise induces angiogenesis but does not alter movement representations within rat motor cortex [J]. Brain Res,2002, 934(1):1-6.
    [38]Ding Y, Li J, Luan X, et al. Exercise pre-conditioning reduces brain damage in ischemic rats that may be associated with regional angiogenesis and cellular overexpression of neurotrophin[J]. Neuroscience,2004,124(3):583-591.
    [39]Hambrecht R, Wolf A, Gielen S, et al. Effect of exercise on coronary endothelial function in patients with coronary artery disease [J]. N Engl J Med,2000, 342(7):454-460.
    [40]Karen G, Josef P, Golo K, et al. Physical Activity Improves Long-Term Stroke Outcome via Endothelial Nitric Oxide Synthase-Dependent Augmentation of Neovascularization and Cerebral Blood Flow [J]. Circ Res,2006,99(10):1132-1140.
    [41]Endres M, Gertz K, Lindauer U, et al. Mechanisms of stroke protection by physical activity [J]. AnnNeurol,2003,54(5):582-590.
    [42]Ploughman M, Granter-Button S, Chernenko G, et al. Exercise intensity influences the temporal profile of growth factors involved in neuronal plasticity following focal ischemia [J]. Brain Res,2007,1150:207-216.
    [43]Dromerick AW, Lang CE, Birkenmeier RL, et al. Very Early Constraint-Induced Movement during Stroke Rehabilitation (VECTORS) A single-center RCT [J]. Neurology,2009,73 (3):195-201.
    [44]Kim YP, Kim HB, Jang MH, et al. Magnitude- and time-dependence of the effect of treadmill exercise on cell proliferation in the dentate gyrus of rats [J]. Int J Sports Med,2003,24(2):114-117.
    [45]Tharp GD. The role of glucocorticoids in exercise [J]. Med Sci Sports Exer, 1975,7(1):6-11.
    [46]Huang AM, Jen CJ, Chen HF, et al. Compulsive exercise acutely upregulates rat hippocampal brain-derived neurotrophic factor [J]. J Neural Transm,2006,113(7): 801-811.
    [47]McIntosh LJ, Sapolsky RM. Glucocorticoids may enhance oxygen radical-mediated neurotoxicity [J]. Neurotoxicology,1996,17(3-4):873-882.
    [48]Brown DA, Johnson MS, Armstrong CJ, et al. Short-term treadmill running in the rat:what kind of stressor is it? [J]. J Appl Physiol,2007,103(6):1979-1985.
    [49]Denise S, Fochesatto C, Helena C, et al. Exercise intensity influences cell injury in rat hippocampal slices exposed to oxygen and glucose deprivation [J]. Brain Research Bulletin,2006,71(1-3):155-159.
    [50]Ramsden M, Berchtold NC, Kesslak JP, et al. Exercise increases the vulnerability of rat hippocampal neurons to kainite lesion [J]. Brain Res,2003,971(2): 239-244.
    [51]Qu M, Mittmann T, Luhmann HJ, et al. Longterm changes of ionotropic glutamate and GABA receptors after unilateral permanent focal cerebral ischemia in the mouse brain [J]. Neuroscience,1998,85(1):29-43.
    [52]Tu WH, Xu X, Peng LS, et al. DAPK1 Interaction with NMD A Receptor NR2B Subunits Mediates Brain Damage in Stroke [J]. Cell,2010,140 (2):222-234.
    [53]Henry GS, Martinand Y, Wang T. Blocking the Deadly Effects of the NMDA Receptor in Stroke [J]. Cell,2010,140 (2):174-176.
    [54]Liu TP, Wong M, Aarts A, et al. NMDA receptor subunits have differential roles in mediating excitotoxic neuronal death both in vitro and in vivo [J]. Journal of Neuroscience,2007,27(11):2846-2857.
    [55]全国第四届脑血管病学术会议.各类脑血管病诊断要点.中华神经科杂志,1996,29(6):379-380.
    [56]Vogel G. New brain cells promopt new theory of depression [J]. Science,2000, 290(13):257-258.
    [57]周士枋.脑卒中后大脑可塑性研究及康复研究[J].中华物理医学与康复杂志,2002,27(7):437-439.
    [58]Hamada T, Hayashi T, Kimura T, et al. Electrical stimulation of human lower extremities enhances energy consumption, carbohydrate oxidation, and whole body glucose uptake [J]. J Appl Phys,2004,96(3):911-916.
    [59]Vitenzon AS, Mironov EM, Petrushanskaya KA. Functional electrostimulation of muscles as a method for restoring motor functions [J]. Neurosci Behav Phys,2005, 35(7):709-714.
    [60]Smith GV, Alon G, Roys SR, et al. Functional MRI determination of a dose-response relationship to lower extremity neuromuscular electrical stimulation in healthy subjects [J]. Exp Brain Res,2003,150(1):33-39.
    [61]郑芳芳.功能性电刺激对脑卒中患者上肢运动功能恢复的fMRI对照研究[D].广州:中山大学,2008.
    [62]Yan TB, Hui-Chan CW, Li LS. Functional electrical stimulation improves motor recovery of the lower extremity and walking ability of subjects with first acute stroke:a randomized placebo-controlled trial [J]. Stroke,2005,36(1):80-85.
    [63]陈秀琼,阳初玉,庞国防,等.早期康复对脑卒中后认知功能影响的研究[J].中国实用神经疾病杂志,2009,12(1):8-11.
    [64]吴毅,胡永善,朱玉连,等.规范化三级康复治疗对脑卒中患者认知功能的影响[J].中国康复医学杂志,2004,19(11):815-819.
    [65]路微波,胡永善,吴毅,等.康复训练改善脑卒中患者认知障碍的临床观 察[J].中国康复医学杂志,2008,23(7):622-624.
    [66]王玉中,王秀霞.认知功能训练对脑卒中后认知障碍患者康复疗效的研究[J].现代预防医学,2010,37(5):957-960.
    [67]Cooper EB, Scherder EJA, Cooper JB. Electrical treatment of reduced consciousness:Experience with coma and Alzheimer's disease [J]. Neuropsychol Rehabil,2005,15(3-4):389-405.
    [68]姜鹭春.信号式功能性电刺激治疗仪在脑卒中偏瘫早期患者康复中的临床应用[D].上海:复旦大学,2008.
    [69]Chae J. Neuromuscular electrical stimulation for motor relearning in hemiparesis [J]. Phys Med Rehabil Clin N Am,2003,14(1 Suppl):S93-109.
    [70]de Kroon JR, Ijzerman MJ, Chae J, et al. Relation between stimulation characteristics and clinical outcome in studies using electrical stimulation to improve motor control of the upper extremity in stroke[J]. J Rehabil Med.2005,37(2):65-74.
    [71]吴毅,安华,朱玉连,等.常规康复治疗结合神经肌肉电刺激对脑卒中患者的疗效观察[J].中国康复医学杂志,2004,19(1):25-27.
    [1]Sugihara H, Moriyoshi K, Ishii T, et al. Structures and properties of seven isoforms of the NMDA receptor generated by alternative splicing [J]. Biochem Biophys Res Commun,1992,185(3):826-832.
    [2]伍国锋,洪震.NMDA受体在突触调控中的作用[J].临床神经电生理学杂志,2009,18(3):182-187.
    [3]Thoflas E, Bartlett NJ, Bannister VJ, et al. Differential roles of NR2A and NR2B-containing NMDA receptors in LTP and LTD in the CA1 region of two week old rat hippocampus [J]. Neuropharmacology,2007,52(1):60-70.
    [4]Clarke RJ, Johnson JW. Voltage—Dependent Gating of NR1 / 2B NMDA Receptors [J]. Physiology,2008,586(23):5727-5741.
    [5]Zhang XL, Sullivan JA, Bloskal JR, et al. A NMDA receptor glycine site partial agonist, GLYX-13, simultaneously enhances LTP and reduces LTD at Schaffer collateral-CA1 synapses in hippocampus [J]. Neuropharmacology,2008, 55(7):1238-1250.
    [6]Sirear R. Developmental maturation of the N-methyl-D-aspartic acid receptor channel complex in postnatal rat brain [J]. Int J Dev Neurosci,2000,8(1): 121-131.
    [7]Low CM, Lyuboslavsky P, French A, et al. Molecular determinants of proton-sensitive N-methyl-D-aspartate receptor gating [J]. Mol Pharmacol,2003, 63(6):1212-1222.
    [8]Banke TG, Dravid SM, Traynelis SF. Protons trap NR1/NR2B NMDA receptors in a nonconducting state [J]. J Neurosci,2005,25(1):42-51.
    [9]Makani S, Chesler M. Endogenous alkaline transients boost postsynaptic NMDA receptor responses in hippocampal CA1 pyramidal neurons [J]. J Neurosci, 2007,27(28):7438-7446.
    [10]Hilgemann DW. Oily barbarians breach ion channel gates [J]. Science,2004, 304(5668):223-224.
    [11]Perozo E, Kloda A, Cortes DM, et al. Physical principles underlying the transduction of bilayer deformation forces during mechanosensitive channel gating [J]. Nat Struct Biol,2002,9(9):696-703.
    [12]Kloda A, Lua L, Hall R, et al. Liposome reconstitution and modulation of recombinant N-methyl-D-aspartate receptor channels by membrane stretch [J]. PNAS,2007,104(5):1540-1545.
    [13]Paoletti P, Ascher P. Mechanosensitivity of NMDA receptors in cultured mouse central neurons [J]. Neuron,1994,13(3):645-655.
    [14]Lyden P, Wahlgren NG. Mechanisms of action of neuroprotectants in stroke [J]. J Stroke Cerebrovasc Dis,2000,9 (6, S2):139-141.
    [15]Chen M, Lu TJ. Differential roles of NMDA receptor subtypes in ischemic neuronal cell death and ischemic tolerance [J]. Stroke,2008,39(11):3042-3048.
    [16]Liu TP, Wong M, Aarts A, et al. NMD A receptor subunits have differential roles in mediating excitotoxic neuronal death both in vitro and in vivo [J]. J Neurosci,2007,27(11):2846-2857.
    [17]Gappoeva MU, Izykenova GA, Granstrem OK, et al. Expression of NMDA neuroreceptors in experimental ischemia [J]. Biochemistry (Moscow),2003,68(6): 696-702.
    [18]Dos AS, Martinez VB, Montori S, et al. Transient global ischemia in rat brain promotes different NMDA receptor regulation depending on the brain structure studied [J]. Neurochem Int,2009,54(3-4):180-185.
    [19]滕大才,徐铁军,张凤真.正常大鼠海马NMDA受体2B亚单位蛋白及其mRNA的平行分布规律[J].徐州医学院学报,2006,26(1):13-16.
    [20]Huang WW, Hu SQ, Li C, et al. Transduced PDZ1 domain of PSD-95 decreases Src phosphorylation and increases nNOS (Ser 847) phosphorylation contributing to neuroprotection after cerebral ischemia [J]. Brain Res,2010,1328: 162-170.
    [21]Hu SQ, Zong YY, Zhang GY, et al. Overexpression of PDZ1 domain of PSD-95 protein rescues hippocampl neurons from apoptosis induced by oxygen-glucose deprivation [J]. Sheng Li Xue Bao,2008,60(6):730-736.
    [22]Cui H, Hayashi A, Sun HS, et al. PDZ protein interactions underlying NMDA receptor-mediated excitotoxicity and neuroprotection by PSD-95 inhibitors [J]. J Neurosci,2007,27(37):9901-9915.
    [23]Hou ST, Jiang SX, Aylsworth A, et al. CaMKII phosphorylates collapsin response mediator protein 2 and modulates axonal damage during glutamate excitotoxicity [J]. J Neurochem,2009,111(3):870-881.
    [24]Gao J, Duan B, Wang DG, et al. Coupling between NMDA receptor and acid-sensing ion channel contributes to ischemic neuronal death [J]. Neuron,2005, 48(4):635-646.
    [25]Hou ST, Jiang SX, Aylsworth A, et al. CaMKⅡ phosphorylates collapsin response mediator protein 2 and modulates axonal damage during glutamate excitotoxicity [J]. J Neurochem,2009,111(3):870-881.
    [26]Saltarelli M, Weaver J, Hsu C, et al. Randomized double-blind, placebo-controlled study to evaluate the safety and efficacy of CP-101606 (traxoprodil), an NR2B-selective N-methyl-d-aspartate antagonist in subjects with acute ischemic stroke [J]. Stroke,2004,35(1):241.
    [27]Cramer SC, Riley JD. Neuroplasticity and brain repair after stroke [J]. Curr Opin Neurol,2008,21(1):76-82.
    [28]Sutcliffe TL, Gaetz WC, Logan WJ, et al. Cortical reorganization after modified constraint-induced movement therapy in pediatric hemiplegic cerebral palsy [J]. J Child Neurol,2007,22(11):1281-1287.
    [29]Dietrich MO, Mantese CE, Porciuncula LO, et al. Exercise affects glutamate receptors in postsynaptic densities from cortical mice brain [J]. Brain Res,2005,1065(1-2):20-25.
    [30]Vaynman S, Ying Z, Gomez PF. Interplay between brainderived neurotrophic factor and signal transduction modulators in the regulation of the effects of exercise on synaptic-plasticity [J]. Neuroscience,2003,122(3): 647-657.
    [31]胡永善,贾杰,吴毅,等.预运动训练对脑梗死大鼠的脑保护作用的兴奋性氨基酸递质效应[J].中国康复医学杂志,2008,23(7):589-593.

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