明胶酶在大鼠坐骨神经挤压伤后的原位酶谱表达
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摘要
目的：临床中的周围神经损伤比较常见。一般分为神经传导障碍、轴索中断及神经中断。临床处理都需要后期的固定。那么为什么固定的时间为3-4周?在这固定期间神经的微观变化都有哪些?神经修复和时间的相关性如何?探讨周围神经挤压损伤后轴突对损伤后的潜在反应，对于帮助神经再生和修复的治疗非常关键。明胶酶参与了细胞外基质的降解、细胞的移行及增殖等有关的神经受损之后修复的所有病理及生理过程，在神经损伤修复后的过程中发挥了重要的作用。本实验以大鼠为研究对象，研究的目的是为了探讨坐骨神经损伤后，神经修复的时间过程中微观的病生理变化，探讨明胶酶A(MMP-2)和明胶酶B(MMP-9)是否有表达以及其可能发挥的作用。
方法：
我们用实验的方法将大鼠的双侧的坐骨神经进行暴露，一侧钳夹持续一分钟，另一侧作为正常对照组(暴露的时间与对侧相同)，从而建立了大鼠坐骨神经挤压损伤的动物模型。
方法一、30只大鼠分为1天、3天、1周、2周和4周共五组。称重后盐酸氯胺酮注射液腹腔注射麻醉，150mg／kg。俯卧位固定四肢于手术台上。双侧腰、臀和股部剃毛，碘伏消毒，铺无菌纱布。两侧臀部各做一斜行切口，并向股后侧延伸。劈开臀肌，分离股二头肌和半膜半腱肌，暴露各组的双侧坐骨神经。在距离梨状肌下缘约8mm处，用反向血管钳钳夹一分钟(左侧为钳夹组，右侧为正常对照组，在手术区域和显露区域丝线标志准确位置)，所有组的正常对照组仅仅暴露，时间与钳夹组相同。0／1丝线缝合臀肌和皮肤。苏醒后送回饲养室给予动物普通饮食，同等条件下饲养。在大鼠坐骨神经挤压损伤后1天、3天、1周、2周和4周时随机取6只大鼠，进行深度麻醉下心脏灌注0．01M的PBS后取材，石蜡包埋切片，光镜下观察损伤后各个时间段内受损神经的病理变化；利用明胶酶谱的测定方法，测定损伤后大鼠坐骨神经组织内的明胶酶A(基质金属蛋白酶2，MMP-2)和明胶酶B(基质金属蛋白酶9，MMP-9)的活性变化；
方法二、15只大鼠随机分为1天、7天和4周共三组。手术方法同一。在大鼠坐骨神经挤压损伤后1天、7天和4周时，深度麻醉下心脏灌注0．01M的PBS后，分离大鼠双侧标志处的坐骨神经，切取神经长度约5-8mm，OCT包埋，立刻放入盛有4℃异戊烷的容器内，浸入液氮2分钟后，放入-25℃冰冻切片机内，切成10微米厚的纵行坐骨神经冰冻切片，粘贴于载玻片上，室温下风干，需做原位酶谱的直接在玻片上滴加反应缓冲液。免疫组织化学染色-20℃冰箱保存待用。用免疫组织化学和原位酶谱的方法观察MMPs在损伤神经轴突中的表达位置及其功能。用于神经胶质酸性蛋白(GFAP)和硫酸软骨素蛋白多糖(CSPG)免疫组织化学的大鼠，在损伤后1周，4周，经4％多聚甲醛心脏灌注后，取大鼠双侧标志处的坐骨神经长约各5-8mm，常规石蜡包埋，纵行切片，了解硫酸软骨素蛋白多糖与瘢痕组织及明胶酶之间可能存在的关系。
结果：
1．大鼠坐骨神经挤压伤之后有不同种类的明胶酶的表达，即明胶酶A和明胶酶B。在挤压伤后的各个阶段光镜下观察，有不同的细胞参与此过程，这与以往的报道一致。明胶酶谱检测的结果显示正常的大鼠坐骨神经组织内有明胶酶A的表达，没有发现明胶酶B的表达。在坐骨神经挤压伤之后的一天内有明胶酶B的迅速表达，而且表达较高。此时光镜下可见到受损区域内有很少的细胞核及血细胞，周围可看到局部中性粒细胞的出现。在伤后的三天可看到起到吞噬作用的炎细胞，至一周时可见减少，与明胶酶B呈现正相关。明胶酶A在受损伤后的表达水平有轻微的增加，到一周时候表达的最高。此时光镜下见到炎细胞较前减少，两周时细胞恢复较多，四周时已经接近正常。Western blot分析进一步确认所消化的条带是明胶酶A和明胶酶B。
2．原位酶谱和免疫组织化学的结果显示基质金属蛋白酶中的明胶酶在损伤区域的边缘有较高的表达，不仅仅如此而且和受损区域内的硫酸软骨素蛋白多糖(CSPG)呈现负相关的趋势。
结论：
1．大鼠坐骨神经损伤后的再生与修复不仅仅有巨噬细胞、雪旺氏细胞等细胞因子存在，同时还有基质金属蛋白酶类的明胶酶参与。在神经受损的第一天，神经周围本身的中性粒细胞有一定程度的反应，此时明胶酶B迅速的上调，保持高水平至三天左右，而此时渗入性的炎细胞大量出现，一周后明胶酶B下降，而明胶酶A表达升高，至四周时明胶酶A、B表达接近正常。提示明胶酶B参与了神经受损后反应的前期阶段，即第一周；而明胶酶A参与了神经修复再生的后期阶段。
2．神经的修复过程宏观上看是髓鞘的退变与再生过程，微观上是众多的细胞因子综合调控的结果。同时有大量降解细胞外基质成分的酶类参与。整个的神经修复过程是4周左右的时间，与临床神经处理术后固定时间吻合。
3．损伤的坐骨神经中心部分有沉积的硫酸软骨素蛋白多糖的存在，明胶酶可能是降解了此成分，从而促进髓鞘的再生过程。
Objective: To investigate the potential response that the axon of the peripheralnerve after crushing injury and it is very important to comprehend the regenerationand reparation of the injuried nerves.The gelatinases participated all the pathologyand physiology processes of the reparations of the injuried nerves includingdegradation of the extracellular, migration and proliferation of the cells,they aresignificant during the recovery of injuried nerves.This experiment is to probe thatthere are whether or not the expression of the gelatinase A and B after the nervecrushing injuried meanwhile the role of them.
Method:we exposed the hibateral sciatic nerves of the rats by means ofexperimental modes,one side was being retained for sixty seconds,the other was justbeing exposed for same time to be the nomal contrl,so we established the rats'ischiadic nerve crushing injuried models.
Method 1.All the rats were allocated into five groups,each group was sixrats.They were weighed and intraperitoneally injected the keanaesthesiad to gotanaesthesia,the dosage was 150mg/kg.The for legs were fixed on the operating-table,shaving the waist,buttocks and thighs,sterilized with povidone iodine,spread thesterilitas gauze.Incised an oblique cut on the bilateralis buttocks and extended to thepost of the femoris.Splited open the gluteus,biceps femoris,semi-membrane andsemitendinosus,exposed the bilateral sciatic nerves.The nerves were ringed clamp forsixty seconds just about 8mm far from the inferior border of musculus piriformis,theleft side was the experimental group and the other side was the normal group andmarked the operative and exposed regions with suture silks.All the rats of normalgroups was cut open to just expose for the same time as that the experimentalgroups'.The gluteus and skins were sutured with 0/1 silks.When they were awake,sentback to the breeding room and gave the animal full diets to breed under thecoordinate conditions.The six rats were sacrificed randomly after the nerve crushinginjury on the first day,three day,one week,two weeks and four weeks,infused 0.01MPBS to draw the materials from the bilateral sciatic nerves,utilized the assay methodof gelatinase enzymogram to mensurate the change of activity of the matrix metalloproteinase 2/9;
Method 2.All 15 rats were allocated to three groups,one day,seven day and 4weeks,each group was five rats.The operation method was same to the anteriorexperiment. The five rats were sacrificed randomly after the nerve crushing injury onthe first day,one week and four weeks,infused 0.01 M PBS to draw the materials fromthe bilateral sciatic nerves,the incised nerve length was 5-8mm,OTC imbeded and putinto the container filled 4℃isopentane liquid immediately,immerged the liquidnitrogen about two minutes,then put into 25℃freezing mictotome and incided thenerve into 10mm thick frozen section portaitly,pasted them on glass slide,air dryingunder the room temperature.The specimen which needed in situ zymograms wasdropwised straightly reaction buffer.The specimen that needed immunohistochemicalstains was conserved in -20℃refrigerator.We observed the expressive sites andfunctions of matrix metalloproteinase in the injured nerve axon.Those specimens thatneeded GFAP and CSPG immunohistochemical imbedded in paraffin routinely andcut sheet to comprehend the possible relations among CSPG,scar tissue and thegelatinases.
Result:1.Variety classes gelatinases were expressed after the rats' ischiadic nervecrushing injury,that was gelatinase A and B.The result of the enzymogram showed thenormal rat ischiadic nerve disply the expression of gelatinase A but not B.Theexpression of gelatinase B after injured 24 houres extremely higher, contradictory thegelatinase A slightly increased post traum and highest on seven days afterinjured. Western blotting inspected the strap were gelatinase A and B.
2.The results of the in situ zymograms and immunohistochemical showednot only gelatinase can be expressed in borderline of the injured area but also betaken on negative correlation to the CSPG in the injured area.
Conclusion:
1.Not only the macrophagocyte, Schwann cells et al cytokines existed aroundinjured nerve axon,but also the gelatinases participated in the regernaeration andreparation of the rat's sciatic nerve injured.
2. Macroscopicly the reparation of the nerve was the process of regeneration anddegeneration of the myelin sheath,in micro it was the result that masses of cell factors regulated them syntheticly.
3.There were chondroitic acid proteoglycan in the center of the injured nerve,thegelatinase maybe degradated them and promoted the regenerative process.
方法：
我们用实验的方法将大鼠的双侧的坐骨神经进行暴露，一侧钳夹持续一分钟，另一侧作为正常对照组(暴露的时间与对侧相同)，从而建立了大鼠坐骨神经挤压损伤的动物模型。
方法一、30只大鼠分为1天、3天、1周、2周和4周共五组。称重后盐酸氯胺酮注射液腹腔注射麻醉，150mg／kg。俯卧位固定四肢于手术台上。双侧腰、臀和股部剃毛，碘伏消毒，铺无菌纱布。两侧臀部各做一斜行切口，并向股后侧延伸。劈开臀肌，分离股二头肌和半膜半腱肌，暴露各组的双侧坐骨神经。在距离梨状肌下缘约8mm处，用反向血管钳钳夹一分钟(左侧为钳夹组，右侧为正常对照组，在手术区域和显露区域丝线标志准确位置)，所有组的正常对照组仅仅暴露，时间与钳夹组相同。0／1丝线缝合臀肌和皮肤。苏醒后送回饲养室给予动物普通饮食，同等条件下饲养。在大鼠坐骨神经挤压损伤后1天、3天、1周、2周和4周时随机取6只大鼠，进行深度麻醉下心脏灌注0．01M的PBS后取材，石蜡包埋切片，光镜下观察损伤后各个时间段内受损神经的病理变化；利用明胶酶谱的测定方法，测定损伤后大鼠坐骨神经组织内的明胶酶A(基质金属蛋白酶2，MMP-2)和明胶酶B(基质金属蛋白酶9，MMP-9)的活性变化；
方法二、15只大鼠随机分为1天、7天和4周共三组。手术方法同一。在大鼠坐骨神经挤压损伤后1天、7天和4周时，深度麻醉下心脏灌注0．01M的PBS后，分离大鼠双侧标志处的坐骨神经，切取神经长度约5-8mm，OCT包埋，立刻放入盛有4℃异戊烷的容器内，浸入液氮2分钟后，放入-25℃冰冻切片机内，切成10微米厚的纵行坐骨神经冰冻切片，粘贴于载玻片上，室温下风干，需做原位酶谱的直接在玻片上滴加反应缓冲液。免疫组织化学染色-20℃冰箱保存待用。用免疫组织化学和原位酶谱的方法观察MMPs在损伤神经轴突中的表达位置及其功能。用于神经胶质酸性蛋白(GFAP)和硫酸软骨素蛋白多糖(CSPG)免疫组织化学的大鼠，在损伤后1周，4周，经4％多聚甲醛心脏灌注后，取大鼠双侧标志处的坐骨神经长约各5-8mm，常规石蜡包埋，纵行切片，了解硫酸软骨素蛋白多糖与瘢痕组织及明胶酶之间可能存在的关系。
结果：
1．大鼠坐骨神经挤压伤之后有不同种类的明胶酶的表达，即明胶酶A和明胶酶B。在挤压伤后的各个阶段光镜下观察，有不同的细胞参与此过程，这与以往的报道一致。明胶酶谱检测的结果显示正常的大鼠坐骨神经组织内有明胶酶A的表达，没有发现明胶酶B的表达。在坐骨神经挤压伤之后的一天内有明胶酶B的迅速表达，而且表达较高。此时光镜下可见到受损区域内有很少的细胞核及血细胞，周围可看到局部中性粒细胞的出现。在伤后的三天可看到起到吞噬作用的炎细胞，至一周时可见减少，与明胶酶B呈现正相关。明胶酶A在受损伤后的表达水平有轻微的增加，到一周时候表达的最高。此时光镜下见到炎细胞较前减少，两周时细胞恢复较多，四周时已经接近正常。Western blot分析进一步确认所消化的条带是明胶酶A和明胶酶B。
2．原位酶谱和免疫组织化学的结果显示基质金属蛋白酶中的明胶酶在损伤区域的边缘有较高的表达，不仅仅如此而且和受损区域内的硫酸软骨素蛋白多糖(CSPG)呈现负相关的趋势。
结论：
1．大鼠坐骨神经损伤后的再生与修复不仅仅有巨噬细胞、雪旺氏细胞等细胞因子存在，同时还有基质金属蛋白酶类的明胶酶参与。在神经受损的第一天，神经周围本身的中性粒细胞有一定程度的反应，此时明胶酶B迅速的上调，保持高水平至三天左右，而此时渗入性的炎细胞大量出现，一周后明胶酶B下降，而明胶酶A表达升高，至四周时明胶酶A、B表达接近正常。提示明胶酶B参与了神经受损后反应的前期阶段，即第一周；而明胶酶A参与了神经修复再生的后期阶段。
2．神经的修复过程宏观上看是髓鞘的退变与再生过程，微观上是众多的细胞因子综合调控的结果。同时有大量降解细胞外基质成分的酶类参与。整个的神经修复过程是4周左右的时间，与临床神经处理术后固定时间吻合。
3．损伤的坐骨神经中心部分有沉积的硫酸软骨素蛋白多糖的存在，明胶酶可能是降解了此成分，从而促进髓鞘的再生过程。
Objective: To investigate the potential response that the axon of the peripheralnerve after crushing injury and it is very important to comprehend the regenerationand reparation of the injuried nerves.The gelatinases participated all the pathologyand physiology processes of the reparations of the injuried nerves includingdegradation of the extracellular, migration and proliferation of the cells,they aresignificant during the recovery of injuried nerves.This experiment is to probe thatthere are whether or not the expression of the gelatinase A and B after the nervecrushing injuried meanwhile the role of them.
Method:we exposed the hibateral sciatic nerves of the rats by means ofexperimental modes,one side was being retained for sixty seconds,the other was justbeing exposed for same time to be the nomal contrl,so we established the rats'ischiadic nerve crushing injuried models.
Method 1.All the rats were allocated into five groups,each group was sixrats.They were weighed and intraperitoneally injected the keanaesthesiad to gotanaesthesia,the dosage was 150mg/kg.The for legs were fixed on the operating-table,shaving the waist,buttocks and thighs,sterilized with povidone iodine,spread thesterilitas gauze.Incised an oblique cut on the bilateralis buttocks and extended to thepost of the femoris.Splited open the gluteus,biceps femoris,semi-membrane andsemitendinosus,exposed the bilateral sciatic nerves.The nerves were ringed clamp forsixty seconds just about 8mm far from the inferior border of musculus piriformis,theleft side was the experimental group and the other side was the normal group andmarked the operative and exposed regions with suture silks.All the rats of normalgroups was cut open to just expose for the same time as that the experimentalgroups'.The gluteus and skins were sutured with 0/1 silks.When they were awake,sentback to the breeding room and gave the animal full diets to breed under thecoordinate conditions.The six rats were sacrificed randomly after the nerve crushinginjury on the first day,three day,one week,two weeks and four weeks,infused 0.01MPBS to draw the materials from the bilateral sciatic nerves,utilized the assay methodof gelatinase enzymogram to mensurate the change of activity of the matrix metalloproteinase 2/9;
Method 2.All 15 rats were allocated to three groups,one day,seven day and 4weeks,each group was five rats.The operation method was same to the anteriorexperiment. The five rats were sacrificed randomly after the nerve crushing injury onthe first day,one week and four weeks,infused 0.01 M PBS to draw the materials fromthe bilateral sciatic nerves,the incised nerve length was 5-8mm,OTC imbeded and putinto the container filled 4℃isopentane liquid immediately,immerged the liquidnitrogen about two minutes,then put into 25℃freezing mictotome and incided thenerve into 10mm thick frozen section portaitly,pasted them on glass slide,air dryingunder the room temperature.The specimen which needed in situ zymograms wasdropwised straightly reaction buffer.The specimen that needed immunohistochemicalstains was conserved in -20℃refrigerator.We observed the expressive sites andfunctions of matrix metalloproteinase in the injured nerve axon.Those specimens thatneeded GFAP and CSPG immunohistochemical imbedded in paraffin routinely andcut sheet to comprehend the possible relations among CSPG,scar tissue and thegelatinases.
Result:1.Variety classes gelatinases were expressed after the rats' ischiadic nervecrushing injury,that was gelatinase A and B.The result of the enzymogram showed thenormal rat ischiadic nerve disply the expression of gelatinase A but not B.Theexpression of gelatinase B after injured 24 houres extremely higher, contradictory thegelatinase A slightly increased post traum and highest on seven days afterinjured. Western blotting inspected the strap were gelatinase A and B.
2.The results of the in situ zymograms and immunohistochemical showednot only gelatinase can be expressed in borderline of the injured area but also betaken on negative correlation to the CSPG in the injured area.
Conclusion:
1.Not only the macrophagocyte, Schwann cells et al cytokines existed aroundinjured nerve axon,but also the gelatinases participated in the regernaeration andreparation of the rat's sciatic nerve injured.
2. Macroscopicly the reparation of the nerve was the process of regeneration anddegeneration of the myelin sheath,in micro it was the result that masses of cell factors regulated them syntheticly.
3.There were chondroitic acid proteoglycan in the center of the injured nerve,thegelatinase maybe degradated them and promoted the regenerative process.
引文
1.Sisken BF,Jacob JM,Walker JL.Acute treatment with pulsed electromagnetic fields and its effect on fast axonal transport in normal and regenerating nerve.J Neurosci Res.1995;42(5):692-699.
2.Park M J,Chung K,Chung JM.Immunohistochemical evidence for sprouting of ventral root afferents after neonatal sciatic neurectomy in the rat.Neurosci Lett.1994;165(1-2):125-128.
3.Hall S.The response to injury in the peripheral nervous system[J].J Bone Joint Surg[Br],2005,87(10):1309-1319.
4.McCAMAN RE,ROBINS E.Biochemical comparison of wallerian degeneration in the central and peripheral nervous systems.Neurology.1958;8(Suppl-1):86-87.
5.Fawcett,J.W.,and R.J.Keynes.Peripheral nerve regeneration.Annu.Rev.Neurosci.1990;13:43-60.
6.Terry RD,Harkin JC.Regenerating peripheral nerve sheaths following wallerian degeneration.Exp Cell Res.1957;13 (1):193-197.
7.Bl(?)mcke S,Niedorf HR.Electron microscope studies of Schwann cells during the Wallerian degeneration with special reference to the cytoplasmic filaments.Acta Neuropathol.1966;6(1):46-60.
8．黄涛，秦建强，刘大庸等．外周神经损伤后许旺细胞激活巨嗜细胞的实验研究[J]．中华显微外科杂志，2002；25(3)：192-193．
9.Olsson Y,Sjrstrand J.Proliferation of mast cells in peripheral nerves during Wallerian degeneration.A radioautographic study.Acta Neuropathol.1969;13 (2):111-121.
10.Collombet JM,Four E,Fauquette W,Burckhart MF,Masqueliez C,Bernab(?) D,Baubichon D,Lallement G.Soman poisoning induces delayed astrogliotic scar and angiogenesis in damaged mouse brain areas.Neurotoxicology.2007;28(1):38-48.
11.Volpi N.Therapeutic applications of glycosaminoglycans.Curr Med Chem.2006;13(15):1799-1810.
12.Sugimoto M,Furuta T,Kodaira C.Polymorphisms of matrix metalloproteinase-7 and chymase are associated with susceptibility to and progression of gastric cancer in Japan.J Gastroenterol. 2008;43(10):751-761.
13. VoonweeYong,Craig A,Krekosk.Matrix metalloProteinases and disease of the CNS. TINS 1998: 212: 75-80.
14. Coxgando,Byrne KJ.Matrix metalloproteinases and caneer. Anticancer Res.2001;21:4207-4219.
15. Mecawley LJ,Matrisian LM.Matrix metalloproteinases:They are not just for matrix any more!Curropin Cell Biol.2001;13:534-540.
16. Clark RA.Synergistic signaling from extracellular matrix-growth factor complexes.J Invest Dermatol. 2008 Jun;128(6):1354-1355.
17. Buss A, Pech K, Kakulas BA.Growth-modulating molecules are associated with invading Schwann cells and not astrocytes in human traumatic spinal cord injury.Brain. 2007;130(Pt 4):940-953.
18. Gantus MA,Nasciutti LE,Cruz CM.Modulation of extracellular matrix components by metalloproteinases and their tissue inhibitors during degeneration and regeneration of rat sural nerve.Brain Res. 2006;29;1122(1):36-46.
19. Everts V,Buttle DJ.Methods in studying ECM degradation.Methods.2008;45(1):86-92.
20. Tripathi R,McTigue DM.Prominent oligodendrocyte genesis along the border of spinal contusion lesions.Glia. 2007;55(7):698-711.
21. Johnson KG,Ghose A,Epstein E.Axonal heparan sulfate proteoglycans regulate the distribution and efficiency of the repellent slit during midline axon guidance.Curr Biol. 2004;23;14(6):499-504.
22. Carulli D,Laabs T,Geller HM,Fawcett JW.Chondroitin sulfate proteoglycans in neural development and regeneration.Curr Opin Neurobiol. 2005 ;15(1): 116-120.
23. Gong Y,Hart E,Shchurin A,Hoover-Plow J.Inflammatory macrophage migration requires MMP-9 activation by plasminogen in mice.J Clin Invest. 2008;118(9):3012-3024.
24. Martini, R. Expression and functional roles of neural cell surface molecules and extracellular matrix components during development and regeneration of peripheral nerves. J.Neurocytol. 1994;23:1-28.
25. Wenjun Zhang and Paul E.Gottsehall.Zymographic measurement of gelatinase activity in brain tissue after detergent extraetion and affinity-support purification.J.Neuroscience Methods 1997; 76 :15-20.
26. Protasov MV, Smagina LV, Galibin OV, Pinaev GP, Voronkina IV.The dependence of MMP-2 and MMP-9 activity in wound fluid on the wound tissue state at initial stages of wound healing process.Tsitologiia. 2008;50(10):882-6.
27. Sanes, JR. Extracellular matrix molecules that influence neural development.Annu. Rev. Neurosci. 1989;12:491-516.
28. Kim YH, Hwang HS, Kim YT, Kim HS, Park YW.Modulation of matrix metalloproteinase secretion by adenosine A3 receptor in preeclamptic villous explants.Reprod Sci. 2008;15(9):939-49.
29. McCawley LJ,Matrisian LM.Matrix metalloproteinases:multifunctional contributors to tumor progression.Mol Med Today,2000;6(4):149-156.
30. Egeblad M,Werb Z.New functions for the matrix metalloproteinases in cancer progression.Nature Rev.Cancer,2002;2(3): 161 -174.
31. Pei D,Kang T,Qi H.Cysteine array matrix metalloproteinase (CA-MMP)/MMP23 is a type II transmembrane matrix metalloproteinase regulated by a single cleavage for both secretion and activation.J Bio Chem,2000;275(43): 3988-3997.
32. Sternlicht MD,Werb Z.How matrix metalloproteinases regulate cell behavior.Annu Rev.Cell DevBiol,2001 ;17:463-516.
33. Yana I,Seiki M.MT-MMPs play pivotal roles in cancer dissemination.Clin Exp Metastasis,2002;19(3):209-215.
34. Koshikawa N,Giannelli G,Cirulli V.Role of cell surface metalloprotease MT1-MMP in epithelial cell migration over laminin-5.J Cell Biol,2000;148(3):615-624.
35. Kajita M,Itoh Y,Chiba T,et al.Membrane-type I matrix metalloproteinase cleaves CD44 and promotes cell migration.J Cell Biol,2001;153(5):893-904.
36. Deryugina El,Ratnikov BI,Postnova TI,et al.Processing of integrin alpha(v) subunit by membrane type I matrix metalloproteinase sti- mulates migration of breast carcinoma cells on vitronectin and enhances tyrosine phosphorylation of focal adhesion kinase. J Biol Chem.2002;277(12);9749-9756.
37. Belkin AM,Akimov SS,Zaritskaya LS,et al.Matrix-dependent proteolysis of surface transglutaminase by membrane-type metalloproteinase regulates cancer cell adhesion and locomotion J Biol Chem,2001;276(21):1415-1422.
38. Tsirka SE,Rogove AD,Striekland S.Neuronal cell death and tPA. Nature, 1996;384(6605): 123-124.
39. Akassoglou K,Koxnbrinck KW,Degen JL,et al.Tissue plasminogen activator-mediated fibrinolysis protects against axonal degene- ration and demyelination after sciatic nerve injury.J Cell Biol,2000,149(5): 1157-1166.
40. Sieonolfi LB,Seeds NW.Mice lacking tPA,uPA,plasminogen genes showed delayed functional recovery after sciatic nerve crush.J Neurosci,2001,21(12):4348-4355.
41. Nabeshima K, Iwasaki H, Nishio J, Koga K, Shishime M, Kikuchi M.Expression of emmprin and matrix metalloproteinases (MMPs) in peripheral nerve sheath tumors: emmprin and membrane-type (MT)1-MMP expressions are associated with malignant potential.Anticancer Res.2006;26(2B):1359-1367.
42. Griffin, JW, DN. Hoffman. Degeneration and regeneration in the peripheral nervous system. In Peripheral Neuropathy. 1993;13:361-376.
43. Pittman, R.N. Release of plasminogen activator and a calcium-dependent metall-oprotease from cultured sympathetic and sensory neurons. Dev. Biol. 1985; 110:91-101.
44. Thomas PK, DG Jones.The cellular response to nerve injury II regeneration of the perineurium after nerve section.J Anat,1967;101:45-55.
45. Sulik A.Matrix metalloproteinases in the central nervous system: clinical significance and therapeutic prospectsPol Merkur Lekarski.2008;24(141): 278-280.
46. Werner SR, Mescher AL,Neff AW,King MW,Chaturvedi S,Duffin KL,Harty MW,Smith RC.Neural MMP-28 expression precedes myelination during development and peripheral nerve repair.Dev Dyn. 2007;236(10):2852-2864.
47. Ulrich R,Gerhauser I,Seeliger F,Baumgartner W,Alldinger S.Matrix metalloproteinases and their inhibitors in the developing mouse brain and spinal cord: a reverse transcription quantitative polymerase chain reaction study.Dev Neurosci. 2005;27(6):408-418.
48. Ahmed Z,Dent RG,Leadbeater WE,Smith C,Berry M,Logan A.Matrix metallop-roteases: degradation of the inhibitory environment of the transected optic nerve and the scar by regenerating axons.Mol Cell Neurosci. 2005;28(1):64-78.
49. Hlawaty H, San Juan A, Jacob MP, Vranckx R, Letourneur D, Feldman LJ.Local matrix metalloproteinase 2 gene knockdown in balloon-injured rabbit carotid arteries using nonviral-small interfering RNA transfection.J Gene Med. 2009; 11(1):92-99.
50. Castellano G,Malaponte G,Mazzarino MC,Figini M,Marchese F,Gangemi P,Travali S,Stivala F,Canevari S,Libra M.Activation of the osteopontin/matrix metalloproteinase-9 pathway correlates with prostate cancer progression.Clin Cancer Res. 2008;15;14(22):7470-7480.
51. Xiong W,Knispel R,Mactaggart J,Baxter BT.Effects of tissue inhibitor of metalloproteinase 2 deficiency on aneurysm formation.J Vasc Surg. 2006;44 (5):1061-1066.
52. Zankl A,Pachman L,Poznanski A,Bonafe L,Wang F,Shusterman Y,Fishman DA,Superti-Furga A.Torg syndrome is caused by inactivating mutations in MMP2 and is allelic to NAO and Winchester syndrome.J Bone Miner Res. 2007;22 (2):329-333.
53. Ochieng J,Fridman R,Nangia-Makker P,Kleiner DE,Liotta LA, Stetler-Stevenson WG,Raz A.Galectin-3 is a novel substrate for human matrix metalloproteinases-2 and -9. Biochemistry. 1994;29;33(47):14109-14114.
54. Kleiner DE,Stetler-Stevenson WG.Quantitative zymography: detection of pico-gram quantities of gelatinases.Anal Biochem. 1994;218(2):325-329.
55. Sei S,Kleiner DE,Kopp JB,Chandra R,Klotman PE,Yarchoan R,Pizzo PA,Mitsuya H.Quantitative analysis of viral burden in tissues from adults and children with symptomatic human immunodeficiency virus type 1 infection assessed by polymerase chain reaction.J Infect Dis. 1994;170(2):325-333.
56. Giannini, C,PJ Dyck.The fate of Schwann cell basement membranes in permanently transected nerves. J.Neuropathol,Exp,Neurol,1990;49:550-563.
57. Yurchenko PD,JC Schittny.Molecular architecture of basement membranes. FASEB J,1990;4:1577-1590.
58. Lorimier P,Mezin MF,Labat N.Ultrastructural localization of the major components of the extracellular matrix in normal rat nerve. J. Histochem. Cytochem. 1992;40:859-868.
59. Ide C,Tohyama R,Yokota T,Nitatori.Schwann cell basal lamina and nerve regene-ration.Brain Res.1983;288:61-75.
60. Reichardt LF,Bixby DE,Hall MJ et al.Integrins and cell adhesion molecules:neuronal receptors that regulate axon growth on extra- cellular matrices and cell surfaces. Dev. Neurosci. 1989;11:332 -347.
61. Pittman RN,Williams AGNeurite penetration into collagen gels requires Ca21-dependentmetalloproteinase activity. Dev. Neurosci.l989;11:41-51.
62. Salles, FJ, N Schechter, S Strickland.A plasminogen activator is induced during goldfish optic nerve regeneration.EMBO (Eur. Mol. Biol. Org.) J. 1990;9:2471-2477.
63. Pagensteeher A,Stalder AK,Klneald CL et al. Differential expression of matrix metalloproteinase and tissue inhibitor of matallo proteinase genes in the mouse central nervous system in normal and inflammatory state.Am J Pathol 1998; 152:729-741.
64. Zuo J,Ferguson TA,Hernadez YJ,et al. Neuronal matrix metallo- proteinase-2 degrade and inactivates a neurite-inhibiting chondroitin sulfate Proteoglyean. J Neurosci 1998; 18: 5203- 5211.
65. Bovolenta P,Wandosell F and Nieto-sampedro M.Charaeterization of a neurite outgrowth inhibitor expressed after CNS injury.Eru J Neurosci. 1993;5:454-465.
66. Kern J,Schrage K,Koopmans GC,Joosten EA,McCaffery P,Mey J. Characterization of retinaldehyde dehydrogenase-2 induction in NG2-positive glia after spinal cord contusion injury.Int J Dev Neurosci. 2007;25(1):7-16.
67. Bruckner G,Pavlica S, Morawski M, Palacios AG, Reichenbach A.Organization of brain extracellular matrix in the Chilean fat-tailed mouse opossum Thylamys elegans (Waterhouse, 1839).J Chem Neuroanat. 2006;32(2-4):143-158.
68. Dino MR,Harroch S,Hockfield S,Matthews RT.Monoclonal antibody Cat-315 detects a glycoform of receptor protein tyrosine phosphatase beta/phosphacan early in CNS development that localizes to extrasynaptic sites prior to synapse formation.Neuroscience. 2006;142(4):1055-1069.
69. Ichihara-Tanaka K,Oohira A,Rumsby M,Muramatsu T.Neuroglycan C is a novel midkine receptor involved in process elongation of oligodendroglial precursor-like cells.J Biol Chem. 2006;281 (41):30857-30864.
70. Beggah AT,Dours-Zimmermann MT,Barras FM,Brosius A,Zimmermann DR,Zurn AD.Lesion-induced differential expression and cell association of Neurocan,Brevican, Versican V1 and V2 in the mouse dorsal root entry zone.Neuroscience.2005;133(3):749-762.
71. Lemons ML,Bania S,Abanto ML,Halfter W,Condic ML.Adaptation of sensory neurons to hyalectin and decorin proteoglycans.J Neurosci.2005;18;25(20): 4964-4973.
72. Ferguson TA and Muir D.MMP-2 and MMP-9 increase the neurite- promoting potential of schwann cell basal laminea and are up- regulated in degenerated nerve.Mol Cell Neurosci 2000;16:157-167.
73. Fiteh MT and Silver J.Activated macrophages and the blood brain barrier: Inflammation after CNS injury leads to inereases in putative inhibitory molecules.Exp Neurol 1997;148:587-603.
74. Maclaren RE.Development and role of retinal glia in regener-ation of ganglion cells following retinal injury.Br J Ophthal 1996;80:458-464.
75. Muir D.MetalloProteinase-dependent neurite outgrowth within a synthetic extracellular matrix is induced by nerve growth factor.Exp Cell Res 1994;210:243-252.
76. McQuarrie IG,Jaeob JM.Conditioning nerve crush accelerate cyto-skeletal protein transport in sprouts that form after a subsequent crush[J].J Comp Neurol, 1991;305(1):139-147.
77. Sjoberg J,Kanje M.The initial period of peripheral nerve regeneration and the importance of the local environment for the conditioning lesion effect[J].Brain Res,1990;529(1-2):79-84.
78. TaPia M,Inestrosa NC,Alvarez J.Early axona lregeneration: repression by Sehwa-nn cells and a protease[J].ExpNeurol,1995;131(1):124-132.
79. Iniguez A,Alvarez J.Isolated axons of Wlds mice regrow centralward [J].Neurosci Lett.l999;268(2):108-110.
80. Ziv NE,Spira ME.Localized and transient elevation of intracellular Ca~(2+) induces the dedifferentiation of axonal segments into growth cones[J].J Neurosci.1997;17(10):3568-3579.
81. Gitler D,Spira ME.Real time imaging of caleium-induced localized proteolytic activity after axotomy and its relation to growth cone formation [J]. Neuron. 1998;20(6):1123-1135.
82. Spira ME,Oren R,Dormann A,et al.Caicium,protease activation and cytoskeleton remodeling underlie growth cone formation and neuron- al regeneration [J].Cell Mol Neurobiol.2001;21(6):591-604.
83. Ziv NE,Spira ME.Induetion of growth cone formation by transient and localized inereases of intracellular proteolytic activity [J].J Cell Biol, 1998; 140(1):223-232.
84. Campenot RB,Eng H.Protein synthesis in axons and its possible functions[J].J Neurocytol,2000;29(11-12):793-798.
85. Zheng JQ,Kelly TK,Chang B,et al.A functional role for intra-axonal protein synthesis during axonal regeneration from adult sensory neurons[J].J Neurosci,2001;21(23):9291-9303.
86. Verma P,Chierzi S,Codd AM,et al.Axonal protein synthesis and degradation are necessary for efficient growth cone regeneration[J].J Neurosci, 2005, 25(2): 331-342.
87. Geddis MS,Rehder V.The phosphorylation state of neuronal processes determines growth cone formation after neuronal injury[J].J Neurosci Res, 2003;74(2): 210-220.
88. Smith SJ.Neuronal cytomechanics:The actin-based motility of growth cones[J].Science,1988;242(4879):708-715.
89. Hsu JY, McKeon R, Goussev S, Werb Z, Lee JU, Trivedi A, et al. Matrix metalloproteinase-2 facilitates wound healing events that promote functional recovery after spinal cord injury. J Neurosci,2006;26:9841-9850.
1. Bellamy TC.Presynaptic modulation of parallel fibre signalling to bergmann glia.Neuropharmacology. 2007;52(2):368-375.
2. Pluto CP,Lane RD,Rhoades RW.Local GABA receptor blockade reveals hindlimb responses in the SI forelimb-stump representation of neonatally amputated rats.J Neurophysiol.2004;92(1):372-379.
3. Matsuda S,Kobayashi N,Mominoki K.Morphological transformation of sensory ganglion neurons and satellite cells.Kaibogaku Zasshi. 1998;73(6):603-613.
4. Perry VH,Tsao JW,Fearn S.Radiation-induced reductions in macrophage recruitment have only slight effects on myelin degeneration in sectioned peripheral nerves of mice.Eur J Neurosci. 1995;7(2):271-280.
5. Armstrong R,Toews AD,Morell P.Axonal transport through nodes of Ranvier.Brain Res.1987;412(1):196-199.
6. Smirnov AV.Distribution of type I,III,IV,V collagen and fibronectin in the extracellular matrix of malignant schwannomas (immuno-morphologic study).ArkhPatol. 1991;53(1):34-39.
7. Wakisaka S,Daikoku H,Miyawaki Y.Immunohistochemical observation of growth associated protein 43 (GAP-43) in the developing circumvallate papilla of the rat.Cell Tissue Res. 1998;293(3): 499-507.
8. Lehning EJ,Persaud A,Dyer KR.Biochemical and morphologic characterization of acrylamide peripheral neuropathy.Toxicol Appl Pharmacol.1998;151(2):211-221.
9. Ernfors P,Ibanez CF,Ebendal T.Molecular cloning and neurotrophic activities of a protein with structural similarities to nerve growth factor: developmental and topographical expression in the brain.Proc Natl Acad Sci USA.1990;87(14):5454.5458.
10. Sakama R,Hiruma H,Kawakami T.Effects of extracellular ATP on axonal transport in cultured mouse dorsal root ganglion neurons.Neuroscience.2003;121:531-535.
11. Jacobson C,Schnapp B,Banker GA.A change in the selective translocation of the Kinesin-1 motor domain marks the initial specification of the axon.Neuron.2006;49:797-804.
12.Domeniconi M,Filbin MT.Overcoming inhibitors in myelin to promote axonal regeneration.Neurol Sci,2005,233:43-47.
13.Adele G,Woolley,Katen J.Developmental loss of NT-3 in vivo results in reduced levels of myelin-specific proteins,a reduced extent of myelination and increased apoptosis of Schwann cells.Glia,2008;56:306-317.
14．于炎冰，张黎．神经导引管与周围神经再生．国外医学神经病学神经外科分册，2000，27(5)：250-252
15.Bunge MB,Bunge RP,Kleitman N.Role of peripheral nerve extra-cellular matrix in Schwann cell function and in neurite regeneration[J].Dev Neurosci,1989,11(45):348-360.
16.Dumont CE,Born W.Stimulation of neurite outgrowth in a human nerve scaffold designed for peripheral nerve reconstruction[J].J Biomed Mater Res B Appl Biomater,2005,73 (1):194-202.
17.O'Daly JA,Imaeda T.Electron microscopic study of wallerian degeneration in cutaneous nerves caused by mechanical injury[J].Lab Invest,1967,17(6):744-748.
18.Pola R,Aprahamia TR,Bosch-Marce M.Age-dependent VEGF expression and intraneural neovascularization during regeneration of peripheral nerves[J].Neurobiol Aging,2004,25(10):1361-1368.
19.Radtke C,Akiyama Y,Lankford KL.Integration of engrafted Schwann cells into injured peripheral nerve:axonal association and nodal formation on regenerated axons.Neurosci Lett.2005;387(2):85-89.
20.Levi AD,Guenard V,Aebischer P.The functional characteristics of Schwann cells cultured from human peripheral nerve after transplantation into a gap within the rat sciatic nerve.J Neurosci.1994;14(3):1309-1319.
21.WEISS P,Hiscoe HB.Experiments on the mechanism of nerve growth.J Exp Zool.1948;107(3):315-395.
22.Weiss P.Neuronal dynamics and axonal flow,cellulifugal transport of labeled neuroplasm in isolated nerve preparations.Proc Natl Acad Sci USA.1967;57(5):1239-1245
23.WEISS P.The life history of the neuron.Res Publ Assoc Res Nerv Ment Dis.1956;35:8-18.
24.Montovani JC,Prado RG,Bacchi CE.Experimental surgery of the facial nerve:Evaluation of the intraperitoneal use of exogenous gangliosides.Rev Laryngol Otol Rhinol.1995;116:163-167.
25.Chen ZY,Chai YF,Cao L.Glial cell line-derived neurotrophic factor enhances axonal regeneration following sciatic nerve transection in adult rats.Brain Res.2001;2:272-276.
26.Tos P,Ronchi G,Nicolino S.Employment of the mouse median nerve model for the experimental assessment of peripheral nerve regeneration.J Neurosci Methods.2008;169 (1):119-127.
27.Cunha MTR,Silva AR,Fenelon SB.Comparision of nerve integration after segmentar resection versus epineural burying in crushed rat sciatic nerves.Acta Cir Bras.1997;4:221-225.
28．赵秀军，章为，王廷华．大鼠脊髓半横断损伤对脊髓Ⅱ板层SP表达的影响．四川大学学报医学版，2005；36：184-186．
29.MurakamiY,Furukawa S,Nitta A.Accumulation of nerve growth factor protein at both rostral and caudal stumps in the transected rat spinal cord.J Neurol Sci,2002;198:63-69.
30.Tobias CA,Han SS,Shumsky JS.Alginate encapsulated BDNF-producing fibroblast grafts permit recovery of function after spinal cord injury in the absence of immune suppression.J Neurotrauma,2005,22:138-156.
31.Conti A,Cardali S,Genovese T.Role of inflammation in the secondary injury following experimental spinal cord trauma.J Neurosurg Sci,2003,47:89-94.
32.HofstetterCP,Holmstrom NA,Lilja JA.Allodynia limits the usefulness of intraspinal neural stem cell grafts,directed differentiation improves outcome.Nat Neurosci,2005,8:346-353.
33.SatakeK,MatsuyamaY,KamiyaM.Up-regulation of glial cell line-derived neurotrophic factor (GDNF) following traumatic spinal cord injury.Neuroreport,2000,11:3877-3881.
34.Khullar SM,Brodin P,Messelt EB.The effects of low level laser treatment on recovery of nerve conduction and motor function after compression injury in the rat sciatic nerve.Eur J Oral Sci. 1995;103(5):299-305.
35. Nahm I,Shin T,Watanabe H.Misdirected regeneration of injured recurrent laryn-geal nerve in the cat.Am J Otolaryngol. 1993 Jan-Feb;14(1):43-48.
36. Kostiuk PGCalcium ion channels in the cell membrane]Fiziol Zh SSSR Im I M Sechenova. 1984;70(8):1081-1091.
37. Ozawa Y,Nakao K,Kurihara T,Shimazaki T.Roles of STAT3/SOCS3 pathway in regulating the visual function and ubiquitin-proteasome-dependent degradation of rhodopsin during retinal inflammation.J Biol Chem. 2008;283(36):24561-24570.
38. Pollard JD.Chronic inflammatory demyelinating polyradiculoneuropathy.Curr Opin Neurol. 2002;15(3):279-283.
39. Fu SY,Gordon T.The Cellular and molecular basis of peripheral nerve regene-ration[J].MolNeurobiol,1997,14(1-2):67-116.
40. Waller A.Experiments on the section of glossopharyngeal and hypoglossal nerves of the frog and observations on the alterations produced thereby in the structure of their primitive fibers. Philos Trans R Soc Lond B Biol Sci, 1850;140:423-429.
41. Fregni F,Conforto AB,Martin MGMagnetic resonance imaging of Wallerian degeneration in stroke.Arch Neurol. 2003;60(10):1466-1467.
42. Kazuho Hirata,Hiroki Mitoma,Noriko Ueno.Differential response of macrophage subpopulations to myelin degradation in the injured rat sciatic nerve[J]. Journal of Neurocytology,1999,28(8):685-695.
43. W Beuche,RL Friede.The role of non-resident cells in Wallerian degeneration[J].Journal of Neurocytology,1984,13(5) :161-196.
44. Henry RG,Oh J,Nelson SJ,Pelletier D.Directional diffusion in relapsing-remitting multiple sclerosis: a possible in vivo signature of Wallerian degeneration.J Magn Reson Imaging. 2003;18(4):420-426.
45. Ramaglia V,King RH,Nourallah M,Wolterman R.The membrane attack complex of the complement system is essential for rapid Wallerian degeneration.J Neurosci.2007;27(29): 7663-7672.
46. Leinhase ISchmidt OIThurman JM,Hossini AM. Pharmacological complement inhibition at the C3 convertase level promotes neuronal survival,neuroprotective intracerebral gene expression and neurological outcome after traumatic brain injury.Exp Neurol 2006,199:454-464.
47.Morgan BP.Measurement of complement hemolytic activity,generation of complement-depleted sera,and production of hemolytic intermediates.Methods Mol Biol 2000,150:61-71.
48.O'Hanlon GM,Humphreys PD,Goldman RS,Halstead SK,Bullens RW,Plomp J J,Ushkaryov Y,Willison HJ.Calpain inhibitors protect against axonal degeneration in a model of antiganglioside antibody-mediated motor nerve terminal injury.Brain.2003,126:2497-2509.
49.Arac D.Structures of neuroligin-1 and the neuroligin-1/neurexin-1 beta complex reveal specific protein-protein and protein-Ca(2+) interactions.Neuron.2007;56:992-1003.
50.Dresbach T,Neeb A,Meyer G,Gundelfinger ED,Brose N.Synaptic targeting of neuroligin is independent of neurexin and SAP90/PSD95 binding.Mol Cell Neurosc.2004;27:227-235.
51.Ramaglia V,Wolterman R,de Kok M,Vigar MA.Soluble complement receptor 1 protects the peripheral nerve from early axon loss after injury.Am J Pathol.2008;172(4):1043-1052.
52.Hirata K,Kawabuchi M.Myelin phagocytosis by macrophages and non macrophages during Wallerian degeneration.Microsc Res Tech.2002;57:541-547.
53.Mueller M,Leonhard C,Wacker K.Macrophage response to peripheral nerve injury:the quantitative contribution of resident and hematogenous macrophages]J].Lab Invest,2003,83(2):175-185.
54.Hirata K,Mitoma H,Ueno N.Differential response of macrophage subpopulation to myelin degradation in the injured rat sciatic nerve]J].J Neurocytol,1999,28(8):685-695.
55.Shen ZL,Lassner F,Beeker M.Cellular activity of resident macrophages during Wallerian degeneration[J].Micro surgery,2000,20(5):255-261.
56．黄涛，秦建强，刘大庸等．外周神经损伤后许旺细胞激活巨噬细胞的实验研究．中华显微外科杂志，2002，25(3)：192-193．
57.Carroll SL,Frohnert PW.Expression of JE(monocyte chemoattractant protein-1) is induced by sciatic axotomy in wild type rodents but not in C57BL/Wld(s) mice[J].J Neuropathol Exp Neurol,1998,57(10):915-930.
58. Sugiura S,Lahav R,Han J.Leukaemia inhibitory factor is required for normal inflammatory responses to injury in the peripheral and central nervous systems in vivo and is chemotactic for macrophages in vitro [J]. Eur J Neurosci, 2000,12(2):457-466.
59. Tofaris G,Patterson P,Jessen K,et al. Denervated Sehwann cell attract macrophages by secretion of leukemia inhibitory factor(LIF) and monocyte chemoattractant protein-1 in a process regulated by interleukin-6 and LIF[J].J Neurosci,2002,22(15):6696-6703.
60. Shamash S,Reiehert F,Rotshenker S. The cytokine network of Wallerian degeneration:tumor necrosis factor-alpha,interleukin-l alpha,and interleukin-1 beta [J]J Neurosci,2002;22(8):3052-3060.
61. Liefner M,Siebert H,Saehse T.The role of TNF-alpha during Wallerian degeneration [J].J Neuroimmunol,2000;108 (1-2):147-152.
62. Atanasoski S,Shumas S,Diekson C.Differential cyelin D requirement of proliferating Sehwann cells during development and after injury [J]. Mol Cell Neurosci,2001;18(6):581-592.
63. Atanasoski S,Boller D,De Ventura L,et al. Cell cycle inhibitors p21 and pl6 are required for the regulation of Sehwann cell proliferation[J].Glia, 2006;53(2):147-157.
64. Inoue M,Rashid MH,Fujita R,Contos JJA,Chun J,Ueda H.Initiation of neuro-pathicpain requires lysophosphatidic acid receptor signaling.Nat Med.2004;10:712-718.
65. Furue H; Katafuchi, T; Yoshimura, M. Sensory processing and functional reorganization of sensory transmission under pathological conditions in the spinal dorsal horn.Neuroscience Research.2004;48:361-368.
66. De Falco M,Fedele V,De Luca L.Evaluation of cyclin D1 expression and its subcellular distribution in mouse tissues[J].J Anat,2004,205(5):405-412.
67. Atanasoski S,Shumas S,Dickson C.Differential cyelin D1 requirements of proliferating Schwann cells during development and after injury[J].Mol Cell Neurosci,2001,18(6):581 -592.
68. Donovan N,Becker EB,Konishi Y,Bonni A.JNK phosphorylation and activation of BAD couples the stress-activated signaling pathway to the cell death machinery. J. Biol. Chem. 2002;277:40944-40949.
69. Verma P,Chierzi S,Codd AM,et al.Axonal protein synthesis and degradation are necessary for efficient growth cone regeneration [J].J Neurosci,2005,25(2):331-342.
70. Romero S,Le Clainche C,Didry D.Formin is a processive motor that requires profilin to accelerate actin assembly and asso-ciated ATP hydrolysis.Cell, 2004,119:419-429.
71. Donovan SL,Mamounas LA,Andrews AM,Blue ME,McCasland JS. GAP-43 is critical for normal development of the serotonergic innervation in forebrain.J Neurosci.2002;22:3543-3552.
72. Hu P,McLachlan EM.Selective reactions of cutaneous and muscle afferent neurons to peripheral nerve transection in rats.J Neurosci.2003; 23(33):10559-10567.
73. Grothe C,Meisinger C,Claus P.In vivo expression and localization of the fibroblast growth factor system in the intact and lesioned rat peripheral nerve and spinal ganglia. J Comp Neurol. 2001;434(3):342-357
74. Kataoka K,Kanje M,Dahlin LB.Induction of activating transcription factor 3 after different sciatic nerve injuries in adult rats.Scand J Plast Reconstr Surg Hand Surg. 2007;41:158-166.
75. Jivan S,Novikova LN,Wiberg M,Novikov LN.The effects of delayed nerve repair on neuronal survival and axonal regeneration after seventh cervical spinal nerve axotomy in adult rats.Exp Brain Res.2005,13:l-10.
76. Lee SR,Tsuji K,Lee SR,Lo EH. Role of matrix metalloproteinases in delayed neuronal damage after transient global cerebral ischemia. J Neurosci 2004;24:671-678.
77. Goussev S,Hsu JY,Lin Y,Tjoa T,Maida N,Werb Z.Differential temporal expression of matrix metalloproteinases after spinal cord injury:relationship to revascularization and wound healing. J Neuro surg Spine 2003;99:188-197.
78. Rosenberg GA.Matrix metalloproteinases in neuroinflammation.Glia 2002;39:279-291.
79. Gasche Y,Fujimura M,Morita-Fujimura Y,Copin JC,Kawase M,Massengale J.Early appearance of activated matrix metalloproteinase-9 after focal cerebral ischemia in mice: a possible role in blood-brain barrier dysfunction. J Cereb Blood Flow Metab 1999;19:1020-1028.
80. Hughes PM,Wells GM,Perry VH,Brown MC,Miller KM.Comparison of matrix metalloproteinase expression during Wallerian degeneration in the central and peripheral nervous systems. Neuroscience 2002; 113:273-287.
81. Fujimura M,Gasche Y,Morita-Fujimura Y,Massengale J,Kawase M,Chan PH.Early appearance of activated matrix metalloproteinase-9 and blood-brain barrier disruption in mice after focal cerebral ischemia and reperfusion. Brain Res 1999;842:92-100.
82. Longo FM,Hayman EG,Davis GE.Neurite-promoting factors and extracellular matrix components accumulating in vivo within nerve regeneration chambers [J].Brain Res,1984,309(1):105-117.
83. De Castro,RC Jr,Burns CL,McAdoo DJ,Romanic AM.Metalloproteinase increases in the injured rat spinal cord. NeuroReport 2000;11:3551-3554.
84. Costanzo RM.Neural regeneration and functional reconnection following olfactory nerve transaction in hamster. Brain Res 1985;361:258-266.
85. Costanzo RM,Perrino LA,Kobayashi M. Response of matrix metalloproteinase-9 to olfactory nerve injury. NeuroReport 2006;17:1787-1791.
86. Hsu JY,McKeon R,Goussev S,Werb Z,Lee JU,Trivedi A.Matrix metallo proteinase-2 facilitates wound healing events that promote functional recovery after spinal cord injury. J Neurosci 2006; 26:9841-9850.
87. McKeon RJ,Hoke A,Silver J.Injury-induced proteoglycans inhibit the potential for laminin-mediated axon growth on astrocytic scars. Exp Neurol 1995; 136:32-43.
88. Moon LD,Asher RA,Rhodes KE,Fawcett JW. Regeneration of CNS axons back to their target following treatment of adult rat brain with chondroitinase ABC.Nat Neurosci 2001;4:465-466.
89.Chau CH,Shum DK,Li H,Pei J,Lui YY,Wirthlin L.Chondroitinase ABC enhances axonal regrowth through Schwann cell-seeded guidance channels after spinal cord injury.FASEB J 2004;18:194-196.
90．郭丽丽，陈言汤，牛扶幼，刘林嶓．病理性瘢痕组织中基质金属蛋白酶-1、金属蛋白酶组织抑制剂-1、血小板源性生长因子、增殖细胞核抗原的表达．郑州大学学报(医学版)．2006；11(6)：1027-1031
91.Schwab JM,Bernard F.Injury reactive myelin/oligodendrocyte-derived axon growth inhibition in the adult mammalian central nervous system.Brain Res Brain Res Rev.2005;49(2):295-299.
92.Collombet JM,Four E,Fauquette W,Burckhart MF,Masqueliez C,Bernab(?) D,Baubichon D,Lallement G.Neurotoxicology.Soman poisoning induces delayed astrogliotic scar and angiogenesis in damaged mouse brain areas.2007;28(1):38-48.
93.Trejo O,Reed JA,Prieto VG.Atypical cells in human cutaneous re-excision scars for melanoma express p75NGFR,C56/N-CAM and GAP-43:evidence of early Schwann cell differentiation.J Cutan Pathol.2002;29(7):397-406.
94.Vroemen M,Caioni M,Bogdahn U,Weidner N.Failure of Schwann cells as suppor-ting cells for adult neural progenitor cell grafts in the acutely injured spinal cord.Cell Tissue Res.2007;327(1):1-13.
95.Reimers N,Zafrakas K,Assmann V,Egen C,Riethdorf L,Riethdorf S,Berger J,Ebel S,J(?)nicke F,Sauter G,Pantel K.Expression of extracellular matrix metallo-proteases inducer on micrometastatic and primary mammary carcinoma cells.Clin Cancer Res.2004;10(10):3422-3428.
96.Krekoski CA,Neubauer D,Graham JB.Metalloproteinase-dependent predegene-ration in vitro enhances axonal regeneration within acellular peripheral nerve grafts[J].J Neurosci,2002;22 (23):10408-10415.
97.Blesch A,Yang H,Weidner N,Hoang A,Otero D.Axonal responses to cellularly delivered NT-4/5 after spinal cord injury.Mol Cell Neurosci.2004;27(2):190-201.
98.Weiner JA,Koo SJ,Nicolas S,Fraboulet S,Pfaff SL,Pourqui(?) O,Sanes JR.Axon fasciculation defects and retinal dysplasias in mice lacking the immunoglobulin superfamily adhesion molecule BEN/ALCAM/SC1.Mol Cell Neurosci.2004;27 (1):59-69.
99. Schmit BD,Hornby TG,Tysseling-Mattiace VM,Benz EN.Absence of local sign withdrawal in chronic human spinal cord injury.J Neurophysiol,2003;90 (5):3232-3241.
100.Littleton JT.Mixing and matching during synaptic vesicle endocytosis.Neuron.2006;51(2):149-151.
101.Origasa M,Tanaka S,Suzuki K,Tone S,Lim B,Koike T.Activation of a novel microglial gene encoding a lysosomal membrane protein in response to neuronal apoptosis.Brain Res Mol Brain Res,2001;88(1-2):1-13.
102.Iremonger KJ,Anderson TR,Hu B,Kiss ZH.Cellular mechanisms preventing sustained activation of cortex during subcortical high-frequency stimulation.J Neurophysiol,2006 ;96(2):613-621.
103.Unlu A,Hariharan N,Iskandar BJ.Spinal cord regeneration induced by a voltage-gated calcium channel agonist.Neurol Res.2002;24(7):639-642.
104.Kita T,Tanaka T,Tanaka N,Kinoshita Y.The role of tumor necrosis factor-alpha in diffuse axonal injury following fluid-percussive brain injury in rats.Int J Legal Med.2000;113(4):221-228.
105.LaFleur M,Underwood JL,Rappolee DA.Base mentmem-brane and repair of injury to peripheral nerve:defining a potential role for macrophages,matrix metalloproteinases and tissue inhibitor of metalloproteinases [J].J Exp Med, 1996;184:2311.
2.Park M J,Chung K,Chung JM.Immunohistochemical evidence for sprouting of ventral root afferents after neonatal sciatic neurectomy in the rat.Neurosci Lett.1994;165(1-2):125-128.
3.Hall S.The response to injury in the peripheral nervous system[J].J Bone Joint Surg[Br],2005,87(10):1309-1319.
4.McCAMAN RE,ROBINS E.Biochemical comparison of wallerian degeneration in the central and peripheral nervous systems.Neurology.1958;8(Suppl-1):86-87.
5.Fawcett,J.W.,and R.J.Keynes.Peripheral nerve regeneration.Annu.Rev.Neurosci.1990;13:43-60.
6.Terry RD,Harkin JC.Regenerating peripheral nerve sheaths following wallerian degeneration.Exp Cell Res.1957;13 (1):193-197.
7.Bl(?)mcke S,Niedorf HR.Electron microscope studies of Schwann cells during the Wallerian degeneration with special reference to the cytoplasmic filaments.Acta Neuropathol.1966;6(1):46-60.
8．黄涛，秦建强，刘大庸等．外周神经损伤后许旺细胞激活巨嗜细胞的实验研究[J]．中华显微外科杂志，2002；25(3)：192-193．
9.Olsson Y,Sjrstrand J.Proliferation of mast cells in peripheral nerves during Wallerian degeneration.A radioautographic study.Acta Neuropathol.1969;13 (2):111-121.
10.Collombet JM,Four E,Fauquette W,Burckhart MF,Masqueliez C,Bernab(?) D,Baubichon D,Lallement G.Soman poisoning induces delayed astrogliotic scar and angiogenesis in damaged mouse brain areas.Neurotoxicology.2007;28(1):38-48.
11.Volpi N.Therapeutic applications of glycosaminoglycans.Curr Med Chem.2006;13(15):1799-1810.
12.Sugimoto M,Furuta T,Kodaira C.Polymorphisms of matrix metalloproteinase-7 and chymase are associated with susceptibility to and progression of gastric cancer in Japan.J Gastroenterol. 2008;43(10):751-761.
13. VoonweeYong,Craig A,Krekosk.Matrix metalloProteinases and disease of the CNS. TINS 1998: 212: 75-80.
14. Coxgando,Byrne KJ.Matrix metalloproteinases and caneer. Anticancer Res.2001;21:4207-4219.
15. Mecawley LJ,Matrisian LM.Matrix metalloproteinases:They are not just for matrix any more!Curropin Cell Biol.2001;13:534-540.
16. Clark RA.Synergistic signaling from extracellular matrix-growth factor complexes.J Invest Dermatol. 2008 Jun;128(6):1354-1355.
17. Buss A, Pech K, Kakulas BA.Growth-modulating molecules are associated with invading Schwann cells and not astrocytes in human traumatic spinal cord injury.Brain. 2007;130(Pt 4):940-953.
18. Gantus MA,Nasciutti LE,Cruz CM.Modulation of extracellular matrix components by metalloproteinases and their tissue inhibitors during degeneration and regeneration of rat sural nerve.Brain Res. 2006;29;1122(1):36-46.
19. Everts V,Buttle DJ.Methods in studying ECM degradation.Methods.2008;45(1):86-92.
20. Tripathi R,McTigue DM.Prominent oligodendrocyte genesis along the border of spinal contusion lesions.Glia. 2007;55(7):698-711.
21. Johnson KG,Ghose A,Epstein E.Axonal heparan sulfate proteoglycans regulate the distribution and efficiency of the repellent slit during midline axon guidance.Curr Biol. 2004;23;14(6):499-504.
22. Carulli D,Laabs T,Geller HM,Fawcett JW.Chondroitin sulfate proteoglycans in neural development and regeneration.Curr Opin Neurobiol. 2005 ;15(1): 116-120.
23. Gong Y,Hart E,Shchurin A,Hoover-Plow J.Inflammatory macrophage migration requires MMP-9 activation by plasminogen in mice.J Clin Invest. 2008;118(9):3012-3024.
24. Martini, R. Expression and functional roles of neural cell surface molecules and extracellular matrix components during development and regeneration of peripheral nerves. J.Neurocytol. 1994;23:1-28.
25. Wenjun Zhang and Paul E.Gottsehall.Zymographic measurement of gelatinase activity in brain tissue after detergent extraetion and affinity-support purification.J.Neuroscience Methods 1997; 76 :15-20.
26. Protasov MV, Smagina LV, Galibin OV, Pinaev GP, Voronkina IV.The dependence of MMP-2 and MMP-9 activity in wound fluid on the wound tissue state at initial stages of wound healing process.Tsitologiia. 2008;50(10):882-6.
27. Sanes, JR. Extracellular matrix molecules that influence neural development.Annu. Rev. Neurosci. 1989;12:491-516.
28. Kim YH, Hwang HS, Kim YT, Kim HS, Park YW.Modulation of matrix metalloproteinase secretion by adenosine A3 receptor in preeclamptic villous explants.Reprod Sci. 2008;15(9):939-49.
29. McCawley LJ,Matrisian LM.Matrix metalloproteinases:multifunctional contributors to tumor progression.Mol Med Today,2000;6(4):149-156.
30. Egeblad M,Werb Z.New functions for the matrix metalloproteinases in cancer progression.Nature Rev.Cancer,2002;2(3): 161 -174.
31. Pei D,Kang T,Qi H.Cysteine array matrix metalloproteinase (CA-MMP)/MMP23 is a type II transmembrane matrix metalloproteinase regulated by a single cleavage for both secretion and activation.J Bio Chem,2000;275(43): 3988-3997.
32. Sternlicht MD,Werb Z.How matrix metalloproteinases regulate cell behavior.Annu Rev.Cell DevBiol,2001 ;17:463-516.
33. Yana I,Seiki M.MT-MMPs play pivotal roles in cancer dissemination.Clin Exp Metastasis,2002;19(3):209-215.
34. Koshikawa N,Giannelli G,Cirulli V.Role of cell surface metalloprotease MT1-MMP in epithelial cell migration over laminin-5.J Cell Biol,2000;148(3):615-624.
35. Kajita M,Itoh Y,Chiba T,et al.Membrane-type I matrix metalloproteinase cleaves CD44 and promotes cell migration.J Cell Biol,2001;153(5):893-904.
36. Deryugina El,Ratnikov BI,Postnova TI,et al.Processing of integrin alpha(v) subunit by membrane type I matrix metalloproteinase sti- mulates migration of breast carcinoma cells on vitronectin and enhances tyrosine phosphorylation of focal adhesion kinase. J Biol Chem.2002;277(12);9749-9756.
37. Belkin AM,Akimov SS,Zaritskaya LS,et al.Matrix-dependent proteolysis of surface transglutaminase by membrane-type metalloproteinase regulates cancer cell adhesion and locomotion J Biol Chem,2001;276(21):1415-1422.
38. Tsirka SE,Rogove AD,Striekland S.Neuronal cell death and tPA. Nature, 1996;384(6605): 123-124.
39. Akassoglou K,Koxnbrinck KW,Degen JL,et al.Tissue plasminogen activator-mediated fibrinolysis protects against axonal degene- ration and demyelination after sciatic nerve injury.J Cell Biol,2000,149(5): 1157-1166.
40. Sieonolfi LB,Seeds NW.Mice lacking tPA,uPA,plasminogen genes showed delayed functional recovery after sciatic nerve crush.J Neurosci,2001,21(12):4348-4355.
41. Nabeshima K, Iwasaki H, Nishio J, Koga K, Shishime M, Kikuchi M.Expression of emmprin and matrix metalloproteinases (MMPs) in peripheral nerve sheath tumors: emmprin and membrane-type (MT)1-MMP expressions are associated with malignant potential.Anticancer Res.2006;26(2B):1359-1367.
42. Griffin, JW, DN. Hoffman. Degeneration and regeneration in the peripheral nervous system. In Peripheral Neuropathy. 1993;13:361-376.
43. Pittman, R.N. Release of plasminogen activator and a calcium-dependent metall-oprotease from cultured sympathetic and sensory neurons. Dev. Biol. 1985; 110:91-101.
44. Thomas PK, DG Jones.The cellular response to nerve injury II regeneration of the perineurium after nerve section.J Anat,1967;101:45-55.
45. Sulik A.Matrix metalloproteinases in the central nervous system: clinical significance and therapeutic prospectsPol Merkur Lekarski.2008;24(141): 278-280.
46. Werner SR, Mescher AL,Neff AW,King MW,Chaturvedi S,Duffin KL,Harty MW,Smith RC.Neural MMP-28 expression precedes myelination during development and peripheral nerve repair.Dev Dyn. 2007;236(10):2852-2864.
47. Ulrich R,Gerhauser I,Seeliger F,Baumgartner W,Alldinger S.Matrix metalloproteinases and their inhibitors in the developing mouse brain and spinal cord: a reverse transcription quantitative polymerase chain reaction study.Dev Neurosci. 2005;27(6):408-418.
48. Ahmed Z,Dent RG,Leadbeater WE,Smith C,Berry M,Logan A.Matrix metallop-roteases: degradation of the inhibitory environment of the transected optic nerve and the scar by regenerating axons.Mol Cell Neurosci. 2005;28(1):64-78.
49. Hlawaty H, San Juan A, Jacob MP, Vranckx R, Letourneur D, Feldman LJ.Local matrix metalloproteinase 2 gene knockdown in balloon-injured rabbit carotid arteries using nonviral-small interfering RNA transfection.J Gene Med. 2009; 11(1):92-99.
50. Castellano G,Malaponte G,Mazzarino MC,Figini M,Marchese F,Gangemi P,Travali S,Stivala F,Canevari S,Libra M.Activation of the osteopontin/matrix metalloproteinase-9 pathway correlates with prostate cancer progression.Clin Cancer Res. 2008;15;14(22):7470-7480.
51. Xiong W,Knispel R,Mactaggart J,Baxter BT.Effects of tissue inhibitor of metalloproteinase 2 deficiency on aneurysm formation.J Vasc Surg. 2006;44 (5):1061-1066.
52. Zankl A,Pachman L,Poznanski A,Bonafe L,Wang F,Shusterman Y,Fishman DA,Superti-Furga A.Torg syndrome is caused by inactivating mutations in MMP2 and is allelic to NAO and Winchester syndrome.J Bone Miner Res. 2007;22 (2):329-333.
53. Ochieng J,Fridman R,Nangia-Makker P,Kleiner DE,Liotta LA, Stetler-Stevenson WG,Raz A.Galectin-3 is a novel substrate for human matrix metalloproteinases-2 and -9. Biochemistry. 1994;29;33(47):14109-14114.
54. Kleiner DE,Stetler-Stevenson WG.Quantitative zymography: detection of pico-gram quantities of gelatinases.Anal Biochem. 1994;218(2):325-329.
55. Sei S,Kleiner DE,Kopp JB,Chandra R,Klotman PE,Yarchoan R,Pizzo PA,Mitsuya H.Quantitative analysis of viral burden in tissues from adults and children with symptomatic human immunodeficiency virus type 1 infection assessed by polymerase chain reaction.J Infect Dis. 1994;170(2):325-333.
56. Giannini, C,PJ Dyck.The fate of Schwann cell basement membranes in permanently transected nerves. J.Neuropathol,Exp,Neurol,1990;49:550-563.
57. Yurchenko PD,JC Schittny.Molecular architecture of basement membranes. FASEB J,1990;4:1577-1590.
58. Lorimier P,Mezin MF,Labat N.Ultrastructural localization of the major components of the extracellular matrix in normal rat nerve. J. Histochem. Cytochem. 1992;40:859-868.
59. Ide C,Tohyama R,Yokota T,Nitatori.Schwann cell basal lamina and nerve regene-ration.Brain Res.1983;288:61-75.
60. Reichardt LF,Bixby DE,Hall MJ et al.Integrins and cell adhesion molecules:neuronal receptors that regulate axon growth on extra- cellular matrices and cell surfaces. Dev. Neurosci. 1989;11:332 -347.
61. Pittman RN,Williams AGNeurite penetration into collagen gels requires Ca21-dependentmetalloproteinase activity. Dev. Neurosci.l989;11:41-51.
62. Salles, FJ, N Schechter, S Strickland.A plasminogen activator is induced during goldfish optic nerve regeneration.EMBO (Eur. Mol. Biol. Org.) J. 1990;9:2471-2477.
63. Pagensteeher A,Stalder AK,Klneald CL et al. Differential expression of matrix metalloproteinase and tissue inhibitor of matallo proteinase genes in the mouse central nervous system in normal and inflammatory state.Am J Pathol 1998; 152:729-741.
64. Zuo J,Ferguson TA,Hernadez YJ,et al. Neuronal matrix metallo- proteinase-2 degrade and inactivates a neurite-inhibiting chondroitin sulfate Proteoglyean. J Neurosci 1998; 18: 5203- 5211.
65. Bovolenta P,Wandosell F and Nieto-sampedro M.Charaeterization of a neurite outgrowth inhibitor expressed after CNS injury.Eru J Neurosci. 1993;5:454-465.
66. Kern J,Schrage K,Koopmans GC,Joosten EA,McCaffery P,Mey J. Characterization of retinaldehyde dehydrogenase-2 induction in NG2-positive glia after spinal cord contusion injury.Int J Dev Neurosci. 2007;25(1):7-16.
67. Bruckner G,Pavlica S, Morawski M, Palacios AG, Reichenbach A.Organization of brain extracellular matrix in the Chilean fat-tailed mouse opossum Thylamys elegans (Waterhouse, 1839).J Chem Neuroanat. 2006;32(2-4):143-158.
68. Dino MR,Harroch S,Hockfield S,Matthews RT.Monoclonal antibody Cat-315 detects a glycoform of receptor protein tyrosine phosphatase beta/phosphacan early in CNS development that localizes to extrasynaptic sites prior to synapse formation.Neuroscience. 2006;142(4):1055-1069.
69. Ichihara-Tanaka K,Oohira A,Rumsby M,Muramatsu T.Neuroglycan C is a novel midkine receptor involved in process elongation of oligodendroglial precursor-like cells.J Biol Chem. 2006;281 (41):30857-30864.
70. Beggah AT,Dours-Zimmermann MT,Barras FM,Brosius A,Zimmermann DR,Zurn AD.Lesion-induced differential expression and cell association of Neurocan,Brevican, Versican V1 and V2 in the mouse dorsal root entry zone.Neuroscience.2005;133(3):749-762.
71. Lemons ML,Bania S,Abanto ML,Halfter W,Condic ML.Adaptation of sensory neurons to hyalectin and decorin proteoglycans.J Neurosci.2005;18;25(20): 4964-4973.
72. Ferguson TA and Muir D.MMP-2 and MMP-9 increase the neurite- promoting potential of schwann cell basal laminea and are up- regulated in degenerated nerve.Mol Cell Neurosci 2000;16:157-167.
73. Fiteh MT and Silver J.Activated macrophages and the blood brain barrier: Inflammation after CNS injury leads to inereases in putative inhibitory molecules.Exp Neurol 1997;148:587-603.
74. Maclaren RE.Development and role of retinal glia in regener-ation of ganglion cells following retinal injury.Br J Ophthal 1996;80:458-464.
75. Muir D.MetalloProteinase-dependent neurite outgrowth within a synthetic extracellular matrix is induced by nerve growth factor.Exp Cell Res 1994;210:243-252.
76. McQuarrie IG,Jaeob JM.Conditioning nerve crush accelerate cyto-skeletal protein transport in sprouts that form after a subsequent crush[J].J Comp Neurol, 1991;305(1):139-147.
77. Sjoberg J,Kanje M.The initial period of peripheral nerve regeneration and the importance of the local environment for the conditioning lesion effect[J].Brain Res,1990;529(1-2):79-84.
78. TaPia M,Inestrosa NC,Alvarez J.Early axona lregeneration: repression by Sehwa-nn cells and a protease[J].ExpNeurol,1995;131(1):124-132.
79. Iniguez A,Alvarez J.Isolated axons of Wlds mice regrow centralward [J].Neurosci Lett.l999;268(2):108-110.
80. Ziv NE,Spira ME.Localized and transient elevation of intracellular Ca~(2+) induces the dedifferentiation of axonal segments into growth cones[J].J Neurosci.1997;17(10):3568-3579.
81. Gitler D,Spira ME.Real time imaging of caleium-induced localized proteolytic activity after axotomy and its relation to growth cone formation [J]. Neuron. 1998;20(6):1123-1135.
82. Spira ME,Oren R,Dormann A,et al.Caicium,protease activation and cytoskeleton remodeling underlie growth cone formation and neuron- al regeneration [J].Cell Mol Neurobiol.2001;21(6):591-604.
83. Ziv NE,Spira ME.Induetion of growth cone formation by transient and localized inereases of intracellular proteolytic activity [J].J Cell Biol, 1998; 140(1):223-232.
84. Campenot RB,Eng H.Protein synthesis in axons and its possible functions[J].J Neurocytol,2000;29(11-12):793-798.
85. Zheng JQ,Kelly TK,Chang B,et al.A functional role for intra-axonal protein synthesis during axonal regeneration from adult sensory neurons[J].J Neurosci,2001;21(23):9291-9303.
86. Verma P,Chierzi S,Codd AM,et al.Axonal protein synthesis and degradation are necessary for efficient growth cone regeneration[J].J Neurosci, 2005, 25(2): 331-342.
87. Geddis MS,Rehder V.The phosphorylation state of neuronal processes determines growth cone formation after neuronal injury[J].J Neurosci Res, 2003;74(2): 210-220.
88. Smith SJ.Neuronal cytomechanics:The actin-based motility of growth cones[J].Science,1988;242(4879):708-715.
89. Hsu JY, McKeon R, Goussev S, Werb Z, Lee JU, Trivedi A, et al. Matrix metalloproteinase-2 facilitates wound healing events that promote functional recovery after spinal cord injury. J Neurosci,2006;26:9841-9850.
1. Bellamy TC.Presynaptic modulation of parallel fibre signalling to bergmann glia.Neuropharmacology. 2007;52(2):368-375.
2. Pluto CP,Lane RD,Rhoades RW.Local GABA receptor blockade reveals hindlimb responses in the SI forelimb-stump representation of neonatally amputated rats.J Neurophysiol.2004;92(1):372-379.
3. Matsuda S,Kobayashi N,Mominoki K.Morphological transformation of sensory ganglion neurons and satellite cells.Kaibogaku Zasshi. 1998;73(6):603-613.
4. Perry VH,Tsao JW,Fearn S.Radiation-induced reductions in macrophage recruitment have only slight effects on myelin degeneration in sectioned peripheral nerves of mice.Eur J Neurosci. 1995;7(2):271-280.
5. Armstrong R,Toews AD,Morell P.Axonal transport through nodes of Ranvier.Brain Res.1987;412(1):196-199.
6. Smirnov AV.Distribution of type I,III,IV,V collagen and fibronectin in the extracellular matrix of malignant schwannomas (immuno-morphologic study).ArkhPatol. 1991;53(1):34-39.
7. Wakisaka S,Daikoku H,Miyawaki Y.Immunohistochemical observation of growth associated protein 43 (GAP-43) in the developing circumvallate papilla of the rat.Cell Tissue Res. 1998;293(3): 499-507.
8. Lehning EJ,Persaud A,Dyer KR.Biochemical and morphologic characterization of acrylamide peripheral neuropathy.Toxicol Appl Pharmacol.1998;151(2):211-221.
9. Ernfors P,Ibanez CF,Ebendal T.Molecular cloning and neurotrophic activities of a protein with structural similarities to nerve growth factor: developmental and topographical expression in the brain.Proc Natl Acad Sci USA.1990;87(14):5454.5458.
10. Sakama R,Hiruma H,Kawakami T.Effects of extracellular ATP on axonal transport in cultured mouse dorsal root ganglion neurons.Neuroscience.2003;121:531-535.
11. Jacobson C,Schnapp B,Banker GA.A change in the selective translocation of the Kinesin-1 motor domain marks the initial specification of the axon.Neuron.2006;49:797-804.
12.Domeniconi M,Filbin MT.Overcoming inhibitors in myelin to promote axonal regeneration.Neurol Sci,2005,233:43-47.
13.Adele G,Woolley,Katen J.Developmental loss of NT-3 in vivo results in reduced levels of myelin-specific proteins,a reduced extent of myelination and increased apoptosis of Schwann cells.Glia,2008;56:306-317.
14．于炎冰，张黎．神经导引管与周围神经再生．国外医学神经病学神经外科分册，2000，27(5)：250-252
15.Bunge MB,Bunge RP,Kleitman N.Role of peripheral nerve extra-cellular matrix in Schwann cell function and in neurite regeneration[J].Dev Neurosci,1989,11(45):348-360.
16.Dumont CE,Born W.Stimulation of neurite outgrowth in a human nerve scaffold designed for peripheral nerve reconstruction[J].J Biomed Mater Res B Appl Biomater,2005,73 (1):194-202.
17.O'Daly JA,Imaeda T.Electron microscopic study of wallerian degeneration in cutaneous nerves caused by mechanical injury[J].Lab Invest,1967,17(6):744-748.
18.Pola R,Aprahamia TR,Bosch-Marce M.Age-dependent VEGF expression and intraneural neovascularization during regeneration of peripheral nerves[J].Neurobiol Aging,2004,25(10):1361-1368.
19.Radtke C,Akiyama Y,Lankford KL.Integration of engrafted Schwann cells into injured peripheral nerve:axonal association and nodal formation on regenerated axons.Neurosci Lett.2005;387(2):85-89.
20.Levi AD,Guenard V,Aebischer P.The functional characteristics of Schwann cells cultured from human peripheral nerve after transplantation into a gap within the rat sciatic nerve.J Neurosci.1994;14(3):1309-1319.
21.WEISS P,Hiscoe HB.Experiments on the mechanism of nerve growth.J Exp Zool.1948;107(3):315-395.
22.Weiss P.Neuronal dynamics and axonal flow,cellulifugal transport of labeled neuroplasm in isolated nerve preparations.Proc Natl Acad Sci USA.1967;57(5):1239-1245
23.WEISS P.The life history of the neuron.Res Publ Assoc Res Nerv Ment Dis.1956;35:8-18.
24.Montovani JC,Prado RG,Bacchi CE.Experimental surgery of the facial nerve:Evaluation of the intraperitoneal use of exogenous gangliosides.Rev Laryngol Otol Rhinol.1995;116:163-167.
25.Chen ZY,Chai YF,Cao L.Glial cell line-derived neurotrophic factor enhances axonal regeneration following sciatic nerve transection in adult rats.Brain Res.2001;2:272-276.
26.Tos P,Ronchi G,Nicolino S.Employment of the mouse median nerve model for the experimental assessment of peripheral nerve regeneration.J Neurosci Methods.2008;169 (1):119-127.
27.Cunha MTR,Silva AR,Fenelon SB.Comparision of nerve integration after segmentar resection versus epineural burying in crushed rat sciatic nerves.Acta Cir Bras.1997;4:221-225.
28．赵秀军，章为，王廷华．大鼠脊髓半横断损伤对脊髓Ⅱ板层SP表达的影响．四川大学学报医学版，2005；36：184-186．
29.MurakamiY,Furukawa S,Nitta A.Accumulation of nerve growth factor protein at both rostral and caudal stumps in the transected rat spinal cord.J Neurol Sci,2002;198:63-69.
30.Tobias CA,Han SS,Shumsky JS.Alginate encapsulated BDNF-producing fibroblast grafts permit recovery of function after spinal cord injury in the absence of immune suppression.J Neurotrauma,2005,22:138-156.
31.Conti A,Cardali S,Genovese T.Role of inflammation in the secondary injury following experimental spinal cord trauma.J Neurosurg Sci,2003,47:89-94.
32.HofstetterCP,Holmstrom NA,Lilja JA.Allodynia limits the usefulness of intraspinal neural stem cell grafts,directed differentiation improves outcome.Nat Neurosci,2005,8:346-353.
33.SatakeK,MatsuyamaY,KamiyaM.Up-regulation of glial cell line-derived neurotrophic factor (GDNF) following traumatic spinal cord injury.Neuroreport,2000,11:3877-3881.
34.Khullar SM,Brodin P,Messelt EB.The effects of low level laser treatment on recovery of nerve conduction and motor function after compression injury in the rat sciatic nerve.Eur J Oral Sci. 1995;103(5):299-305.
35. Nahm I,Shin T,Watanabe H.Misdirected regeneration of injured recurrent laryn-geal nerve in the cat.Am J Otolaryngol. 1993 Jan-Feb;14(1):43-48.
36. Kostiuk PGCalcium ion channels in the cell membrane]Fiziol Zh SSSR Im I M Sechenova. 1984;70(8):1081-1091.
37. Ozawa Y,Nakao K,Kurihara T,Shimazaki T.Roles of STAT3/SOCS3 pathway in regulating the visual function and ubiquitin-proteasome-dependent degradation of rhodopsin during retinal inflammation.J Biol Chem. 2008;283(36):24561-24570.
38. Pollard JD.Chronic inflammatory demyelinating polyradiculoneuropathy.Curr Opin Neurol. 2002;15(3):279-283.
39. Fu SY,Gordon T.The Cellular and molecular basis of peripheral nerve regene-ration[J].MolNeurobiol,1997,14(1-2):67-116.
40. Waller A.Experiments on the section of glossopharyngeal and hypoglossal nerves of the frog and observations on the alterations produced thereby in the structure of their primitive fibers. Philos Trans R Soc Lond B Biol Sci, 1850;140:423-429.
41. Fregni F,Conforto AB,Martin MGMagnetic resonance imaging of Wallerian degeneration in stroke.Arch Neurol. 2003;60(10):1466-1467.
42. Kazuho Hirata,Hiroki Mitoma,Noriko Ueno.Differential response of macrophage subpopulations to myelin degradation in the injured rat sciatic nerve[J]. Journal of Neurocytology,1999,28(8):685-695.
43. W Beuche,RL Friede.The role of non-resident cells in Wallerian degeneration[J].Journal of Neurocytology,1984,13(5) :161-196.
44. Henry RG,Oh J,Nelson SJ,Pelletier D.Directional diffusion in relapsing-remitting multiple sclerosis: a possible in vivo signature of Wallerian degeneration.J Magn Reson Imaging. 2003;18(4):420-426.
45. Ramaglia V,King RH,Nourallah M,Wolterman R.The membrane attack complex of the complement system is essential for rapid Wallerian degeneration.J Neurosci.2007;27(29): 7663-7672.
46. Leinhase ISchmidt OIThurman JM,Hossini AM. Pharmacological complement inhibition at the C3 convertase level promotes neuronal survival,neuroprotective intracerebral gene expression and neurological outcome after traumatic brain injury.Exp Neurol 2006,199:454-464.
47.Morgan BP.Measurement of complement hemolytic activity,generation of complement-depleted sera,and production of hemolytic intermediates.Methods Mol Biol 2000,150:61-71.
48.O'Hanlon GM,Humphreys PD,Goldman RS,Halstead SK,Bullens RW,Plomp J J,Ushkaryov Y,Willison HJ.Calpain inhibitors protect against axonal degeneration in a model of antiganglioside antibody-mediated motor nerve terminal injury.Brain.2003,126:2497-2509.
49.Arac D.Structures of neuroligin-1 and the neuroligin-1/neurexin-1 beta complex reveal specific protein-protein and protein-Ca(2+) interactions.Neuron.2007;56:992-1003.
50.Dresbach T,Neeb A,Meyer G,Gundelfinger ED,Brose N.Synaptic targeting of neuroligin is independent of neurexin and SAP90/PSD95 binding.Mol Cell Neurosc.2004;27:227-235.
51.Ramaglia V,Wolterman R,de Kok M,Vigar MA.Soluble complement receptor 1 protects the peripheral nerve from early axon loss after injury.Am J Pathol.2008;172(4):1043-1052.
52.Hirata K,Kawabuchi M.Myelin phagocytosis by macrophages and non macrophages during Wallerian degeneration.Microsc Res Tech.2002;57:541-547.
53.Mueller M,Leonhard C,Wacker K.Macrophage response to peripheral nerve injury:the quantitative contribution of resident and hematogenous macrophages]J].Lab Invest,2003,83(2):175-185.
54.Hirata K,Mitoma H,Ueno N.Differential response of macrophage subpopulation to myelin degradation in the injured rat sciatic nerve]J].J Neurocytol,1999,28(8):685-695.
55.Shen ZL,Lassner F,Beeker M.Cellular activity of resident macrophages during Wallerian degeneration[J].Micro surgery,2000,20(5):255-261.
56．黄涛，秦建强，刘大庸等．外周神经损伤后许旺细胞激活巨噬细胞的实验研究．中华显微外科杂志，2002，25(3)：192-193．
57.Carroll SL,Frohnert PW.Expression of JE(monocyte chemoattractant protein-1) is induced by sciatic axotomy in wild type rodents but not in C57BL/Wld(s) mice[J].J Neuropathol Exp Neurol,1998,57(10):915-930.
58. Sugiura S,Lahav R,Han J.Leukaemia inhibitory factor is required for normal inflammatory responses to injury in the peripheral and central nervous systems in vivo and is chemotactic for macrophages in vitro [J]. Eur J Neurosci, 2000,12(2):457-466.
59. Tofaris G,Patterson P,Jessen K,et al. Denervated Sehwann cell attract macrophages by secretion of leukemia inhibitory factor(LIF) and monocyte chemoattractant protein-1 in a process regulated by interleukin-6 and LIF[J].J Neurosci,2002,22(15):6696-6703.
60. Shamash S,Reiehert F,Rotshenker S. The cytokine network of Wallerian degeneration:tumor necrosis factor-alpha,interleukin-l alpha,and interleukin-1 beta [J]J Neurosci,2002;22(8):3052-3060.
61. Liefner M,Siebert H,Saehse T.The role of TNF-alpha during Wallerian degeneration [J].J Neuroimmunol,2000;108 (1-2):147-152.
62. Atanasoski S,Shumas S,Diekson C.Differential cyelin D requirement of proliferating Sehwann cells during development and after injury [J]. Mol Cell Neurosci,2001;18(6):581-592.
63. Atanasoski S,Boller D,De Ventura L,et al. Cell cycle inhibitors p21 and pl6 are required for the regulation of Sehwann cell proliferation[J].Glia, 2006;53(2):147-157.
64. Inoue M,Rashid MH,Fujita R,Contos JJA,Chun J,Ueda H.Initiation of neuro-pathicpain requires lysophosphatidic acid receptor signaling.Nat Med.2004;10:712-718.
65. Furue H; Katafuchi, T; Yoshimura, M. Sensory processing and functional reorganization of sensory transmission under pathological conditions in the spinal dorsal horn.Neuroscience Research.2004;48:361-368.
66. De Falco M,Fedele V,De Luca L.Evaluation of cyclin D1 expression and its subcellular distribution in mouse tissues[J].J Anat,2004,205(5):405-412.
67. Atanasoski S,Shumas S,Dickson C.Differential cyelin D1 requirements of proliferating Schwann cells during development and after injury[J].Mol Cell Neurosci,2001,18(6):581 -592.
68. Donovan N,Becker EB,Konishi Y,Bonni A.JNK phosphorylation and activation of BAD couples the stress-activated signaling pathway to the cell death machinery. J. Biol. Chem. 2002;277:40944-40949.
69. Verma P,Chierzi S,Codd AM,et al.Axonal protein synthesis and degradation are necessary for efficient growth cone regeneration [J].J Neurosci,2005,25(2):331-342.
70. Romero S,Le Clainche C,Didry D.Formin is a processive motor that requires profilin to accelerate actin assembly and asso-ciated ATP hydrolysis.Cell, 2004,119:419-429.
71. Donovan SL,Mamounas LA,Andrews AM,Blue ME,McCasland JS. GAP-43 is critical for normal development of the serotonergic innervation in forebrain.J Neurosci.2002;22:3543-3552.
72. Hu P,McLachlan EM.Selective reactions of cutaneous and muscle afferent neurons to peripheral nerve transection in rats.J Neurosci.2003; 23(33):10559-10567.
73. Grothe C,Meisinger C,Claus P.In vivo expression and localization of the fibroblast growth factor system in the intact and lesioned rat peripheral nerve and spinal ganglia. J Comp Neurol. 2001;434(3):342-357
74. Kataoka K,Kanje M,Dahlin LB.Induction of activating transcription factor 3 after different sciatic nerve injuries in adult rats.Scand J Plast Reconstr Surg Hand Surg. 2007;41:158-166.
75. Jivan S,Novikova LN,Wiberg M,Novikov LN.The effects of delayed nerve repair on neuronal survival and axonal regeneration after seventh cervical spinal nerve axotomy in adult rats.Exp Brain Res.2005,13:l-10.
76. Lee SR,Tsuji K,Lee SR,Lo EH. Role of matrix metalloproteinases in delayed neuronal damage after transient global cerebral ischemia. J Neurosci 2004;24:671-678.
77. Goussev S,Hsu JY,Lin Y,Tjoa T,Maida N,Werb Z.Differential temporal expression of matrix metalloproteinases after spinal cord injury:relationship to revascularization and wound healing. J Neuro surg Spine 2003;99:188-197.
78. Rosenberg GA.Matrix metalloproteinases in neuroinflammation.Glia 2002;39:279-291.
79. Gasche Y,Fujimura M,Morita-Fujimura Y,Copin JC,Kawase M,Massengale J.Early appearance of activated matrix metalloproteinase-9 after focal cerebral ischemia in mice: a possible role in blood-brain barrier dysfunction. J Cereb Blood Flow Metab 1999;19:1020-1028.
80. Hughes PM,Wells GM,Perry VH,Brown MC,Miller KM.Comparison of matrix metalloproteinase expression during Wallerian degeneration in the central and peripheral nervous systems. Neuroscience 2002; 113:273-287.
81. Fujimura M,Gasche Y,Morita-Fujimura Y,Massengale J,Kawase M,Chan PH.Early appearance of activated matrix metalloproteinase-9 and blood-brain barrier disruption in mice after focal cerebral ischemia and reperfusion. Brain Res 1999;842:92-100.
82. Longo FM,Hayman EG,Davis GE.Neurite-promoting factors and extracellular matrix components accumulating in vivo within nerve regeneration chambers [J].Brain Res,1984,309(1):105-117.
83. De Castro,RC Jr,Burns CL,McAdoo DJ,Romanic AM.Metalloproteinase increases in the injured rat spinal cord. NeuroReport 2000;11:3551-3554.
84. Costanzo RM.Neural regeneration and functional reconnection following olfactory nerve transaction in hamster. Brain Res 1985;361:258-266.
85. Costanzo RM,Perrino LA,Kobayashi M. Response of matrix metalloproteinase-9 to olfactory nerve injury. NeuroReport 2006;17:1787-1791.
86. Hsu JY,McKeon R,Goussev S,Werb Z,Lee JU,Trivedi A.Matrix metallo proteinase-2 facilitates wound healing events that promote functional recovery after spinal cord injury. J Neurosci 2006; 26:9841-9850.
87. McKeon RJ,Hoke A,Silver J.Injury-induced proteoglycans inhibit the potential for laminin-mediated axon growth on astrocytic scars. Exp Neurol 1995; 136:32-43.
88. Moon LD,Asher RA,Rhodes KE,Fawcett JW. Regeneration of CNS axons back to their target following treatment of adult rat brain with chondroitinase ABC.Nat Neurosci 2001;4:465-466.
89.Chau CH,Shum DK,Li H,Pei J,Lui YY,Wirthlin L.Chondroitinase ABC enhances axonal regrowth through Schwann cell-seeded guidance channels after spinal cord injury.FASEB J 2004;18:194-196.
90．郭丽丽，陈言汤，牛扶幼，刘林嶓．病理性瘢痕组织中基质金属蛋白酶-1、金属蛋白酶组织抑制剂-1、血小板源性生长因子、增殖细胞核抗原的表达．郑州大学学报(医学版)．2006；11(6)：1027-1031
91.Schwab JM,Bernard F.Injury reactive myelin/oligodendrocyte-derived axon growth inhibition in the adult mammalian central nervous system.Brain Res Brain Res Rev.2005;49(2):295-299.
92.Collombet JM,Four E,Fauquette W,Burckhart MF,Masqueliez C,Bernab(?) D,Baubichon D,Lallement G.Neurotoxicology.Soman poisoning induces delayed astrogliotic scar and angiogenesis in damaged mouse brain areas.2007;28(1):38-48.
93.Trejo O,Reed JA,Prieto VG.Atypical cells in human cutaneous re-excision scars for melanoma express p75NGFR,C56/N-CAM and GAP-43:evidence of early Schwann cell differentiation.J Cutan Pathol.2002;29(7):397-406.
94.Vroemen M,Caioni M,Bogdahn U,Weidner N.Failure of Schwann cells as suppor-ting cells for adult neural progenitor cell grafts in the acutely injured spinal cord.Cell Tissue Res.2007;327(1):1-13.
95.Reimers N,Zafrakas K,Assmann V,Egen C,Riethdorf L,Riethdorf S,Berger J,Ebel S,J(?)nicke F,Sauter G,Pantel K.Expression of extracellular matrix metallo-proteases inducer on micrometastatic and primary mammary carcinoma cells.Clin Cancer Res.2004;10(10):3422-3428.
96.Krekoski CA,Neubauer D,Graham JB.Metalloproteinase-dependent predegene-ration in vitro enhances axonal regeneration within acellular peripheral nerve grafts[J].J Neurosci,2002;22 (23):10408-10415.
97.Blesch A,Yang H,Weidner N,Hoang A,Otero D.Axonal responses to cellularly delivered NT-4/5 after spinal cord injury.Mol Cell Neurosci.2004;27(2):190-201.
98.Weiner JA,Koo SJ,Nicolas S,Fraboulet S,Pfaff SL,Pourqui(?) O,Sanes JR.Axon fasciculation defects and retinal dysplasias in mice lacking the immunoglobulin superfamily adhesion molecule BEN/ALCAM/SC1.Mol Cell Neurosci.2004;27 (1):59-69.
99. Schmit BD,Hornby TG,Tysseling-Mattiace VM,Benz EN.Absence of local sign withdrawal in chronic human spinal cord injury.J Neurophysiol,2003;90 (5):3232-3241.
100.Littleton JT.Mixing and matching during synaptic vesicle endocytosis.Neuron.2006;51(2):149-151.
101.Origasa M,Tanaka S,Suzuki K,Tone S,Lim B,Koike T.Activation of a novel microglial gene encoding a lysosomal membrane protein in response to neuronal apoptosis.Brain Res Mol Brain Res,2001;88(1-2):1-13.
102.Iremonger KJ,Anderson TR,Hu B,Kiss ZH.Cellular mechanisms preventing sustained activation of cortex during subcortical high-frequency stimulation.J Neurophysiol,2006 ;96(2):613-621.
103.Unlu A,Hariharan N,Iskandar BJ.Spinal cord regeneration induced by a voltage-gated calcium channel agonist.Neurol Res.2002;24(7):639-642.
104.Kita T,Tanaka T,Tanaka N,Kinoshita Y.The role of tumor necrosis factor-alpha in diffuse axonal injury following fluid-percussive brain injury in rats.Int J Legal Med.2000;113(4):221-228.
105.LaFleur M,Underwood JL,Rappolee DA.Base mentmem-brane and repair of injury to peripheral nerve:defining a potential role for macrophages,matrix metalloproteinases and tissue inhibitor of metalloproteinases [J].J Exp Med, 1996;184:2311.