未成熟大鼠实验性缺氧缺血性脑白质损伤中F-actin和RhoA的表达变化及毛喉素对神经细胞骨架保护作用探讨
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摘要
第一部分 未成熟大鼠实验性缺氧缺血性脑白质损伤(WMD)模型的建立与评价
目的：建立未成熟大鼠缺氧缺血性脑白质损伤(white matter damage，WMD)模型并对其可行性进行评价。
方法：2日龄SD大鼠随机分为WMD组和对照组，WMD组经右侧颈总动脉扎，术后予以6％O_2、94％N_2混合气体处理4h，以建立WMD的动物模型。对照组仅分离右侧颈总动脉，不予结扎和缺氧处理。用HE染色观察脑组织病理学变化，电镜观察超微结构改变。1m时对WMD组大鼠进行神经行为学评价。
结果：(1) 缺氧缺血(hypoxia-ischemia，HI)后各时段WMD组均观察到右侧脑白质神经细胞(主要观察胼胝体区)较对照组不同程度
The first part: Establishment and evaluation of WMD model in premature rats
Objective:To establish the hypoxic-ischemic WMD model in premature rats and evaluate its feasibility.
Methods:The 2 day-old SD rats were subjected to the ligation of right carotid artery(ischemia),and then they were put into a box full with 6% oxygen and 94% nitrogen for 4 hours(hypoxia).The light microscope was used to observe the brain pathological changes and the electron microscope was used to detect the brain ultrastructural changes after hypoxia and ischemia (HI) . Evaluate the rats at 1 month through psycho-behavior methods. T test was utilized to
目的：建立未成熟大鼠缺氧缺血性脑白质损伤(white matter damage，WMD)模型并对其可行性进行评价。
方法：2日龄SD大鼠随机分为WMD组和对照组，WMD组经右侧颈总动脉扎，术后予以6％O_2、94％N_2混合气体处理4h，以建立WMD的动物模型。对照组仅分离右侧颈总动脉，不予结扎和缺氧处理。用HE染色观察脑组织病理学变化，电镜观察超微结构改变。1m时对WMD组大鼠进行神经行为学评价。
结果：(1) 缺氧缺血(hypoxia-ischemia，HI)后各时段WMD组均观察到右侧脑白质神经细胞(主要观察胼胝体区)较对照组不同程度
The first part: Establishment and evaluation of WMD model in premature rats
Objective:To establish the hypoxic-ischemic WMD model in premature rats and evaluate its feasibility.
Methods:The 2 day-old SD rats were subjected to the ligation of right carotid artery(ischemia),and then they were put into a box full with 6% oxygen and 94% nitrogen for 4 hours(hypoxia).The light microscope was used to observe the brain pathological changes and the electron microscope was used to detect the brain ultrastructural changes after hypoxia and ischemia (HI) . Evaluate the rats at 1 month through psycho-behavior methods. T test was utilized to
引文
1 陈惠金．早产儿脑室周围白质软化的研究进展．实用儿科临床杂志．2004，19(2)：83-86．
2 Rice J, Vannucci R, Brierly J. The influence of immaturity on hypoxia-ischemic brain damage in the rat. Ann Neurol. 1981, 9: 131-141
3 Back SA, Han BH, Luo NL, et al. Selective vulnerability of late oligodendrocyte progenitors to hypoxia-ischemia. J Neurosci. 2002, 22(2): 455-463
4 Paxinos G, Waston C. The rat brain in stereotaxic coordinate. 3rd Edition. Academic Press, Sydney, 1998.
5 Chang YS, Mu DZ, Michael WE, et al. Erythropoietin improves functional and histological outcome in neonatal stroke. Pediatric Res, 2005, 58(1): 106-11
6 袁宝莉，李瑞林，等．新生大鼠脑白质损害模型的建立与评价．新生儿科杂志，2004，19(1)：17-19．
7 Back SA, Luo NL, Borenstein NS, et al. Late oligodendrocyte progenitors coincide with the development window of volunerability for human perinatal white matter injury. J of Neurosci, 2001, 21(4): 1302-12.
8 Cai Z, Pang Y, Xiao F, et al. Chronic ischemia preferentially causes white matter injury in the neonatal rat brain. Brain Res, 2001, 898: 126-35.
9 Kohlhauser C, Mosgoller W, Hoger H, et al. Myelination deficits in brain of rats following perinatal asphyxia. Life Sci, 2000, 67: 2355-68.
10 Redecker C, Hagemann G, Marret S, et al. Long-term evolution of excitotoxic cortical dysgenesis induced in the developing rat brain. Dev Brain Res, 1998, 109: 109-13.
11 Husson I, Mesples B, Bac P, et al. Melatoninergic neuroprotection of the murine periventricular white matter against neonatal excitotoxic challenge. Ann Neurol, 2002, 52: 82-92.
1 余波，姚裕家，等．缺血再灌注损伤对新生鼠肾小管上皮细胞F-actin的影响．上海第二医科大学学报．2004，24：365-70．
2 Aspenstoom P, Fransson A, Saras J. Rho GTPases have diverse effects on the organization of the actin filament system. Biochem, 2004, 337: 327-37.
3 Takai Y, Sasaki T, Motozaki T. Small GTP-binding proteins. Physiol REV, 2001, 81: 153-208.
4 Estienne-Mannevide S, Hall A. Rho GTPase in cell biology. Nature, 2002, 420: 629-35.
5 Wojciak-Stothard B, Tsang LY, Haworth SG. Rac and Rho play opposing roles in the regulation of hypoxia/reoxygenation-induced permeability changes in pulmonary artery endothelial cells. American Journal of Physiology, 2005, 288(14): 749-60.
6 Nobes CD, Hall A. Rho, rac and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia and filopodia. Cell, 2001, 81: 53-62.
7 王华，姚裕家，陈大鹏．缺氧缺血新生鼠脑组织Ng-R含量变化．四川医学，2005，26(4)：362-64．
8 Benitez-King G, Ramires-Rodrigue G. The neuronal cytal cytoskeleton as a potential therapeutical target in neurodegenerative disease and schizaphrenia. Current Drug Targets, 2004, 3(6): 515-33.
9 Niederost B, Oertle T, Fritsche J, etal. Nogo-A and myelin-associated glycoprotein mediate neurite growth inhibition by antagonistic regulation of RhoA and Racl. J of Neurosci, 2002, 22(23): 10368-76.
10 Yin HL, Stoil JT. Proteins that regulate dynamics actin remodeling. in response to membrane signaling minireview series. J of Biol Chem, 1999, 274(46): 32529-30.
11 Cheryl L, Gantto, Barbara J. Local ERM activation and dynamic growth cones at Schwann cell tips implicated in efficient of nodes of Ranvier. The Journal of Cell Biology, 2003, 162(3): 489-98.
12 Raman N, Atkinson SJ. Rho controls actin cytoskeletal assembly in renal epithelial cells during ATP depletion and recovery. American Journal of Physiology, 1999, 276(6): 1312-24.
13 Yoshiyuki T, Emi NA, et al. Proteolysis of neuronal cytoskeletal proteins by calpain contributes to rat retina cell death induced by hypopxia. Brain Research, 2005, 1050: 148-55.
14 Mashima T, Naito M, Tsuruo T. Caspase-mediated cleavage of eytoskeleton actin plays a positive role in the process of morphological apoptosis. Oncogene, 1999, 18(15): 2423-30.
1 Foumier AE, Taldzawa BT, Strittmatter SM. Rho kinase inhibiton enhances axonal regeneration in the injured CNS. J of Neurosci, 2003, 23: 1416-23.
2 Hastie LE, Patton WF, Hechtman HB, et al. H_2O_2 induced filamin redistribution in endothelia cell is modulated by the cyclic AMP-dependant protein kinase pathway. J of Cell Physiol, 1997, 172(3): 373-81.
3 Jin Qiu, Dongming Cai, Haining Dai, et al. Spinal axon regeneration indeced by elevation of cyclic AMP. Neuron, 2002, 34: 895-903.
4 Dongming Cai, Kangwen Deng, Wilfredo M, et al. Arginase Ⅰ and polyamines act downstream from cAMP in overcoming inhibition of axonal growth MAG and myelin in vitro. Neuron, 2002, 35: 711-19.
5 Soto I, Rosentha JJ, Blagbum JM, Blanco RE. Fibroblast growth factors 2 applied to the optic nerve after axotomy up-regulates BDNF and TrkB in ganglion cells by activation the ERK and PKA signaling pathways. Journal of Neurochemistry, 2006, 96(1): 82-96.
6 李良平，徐如祥，等．脑损伤后血脑屏障损害的信号传导机制研究．第一军医大学学报，2001，21(9)：659-61．
7 Perez V, Bouschet T, Fernandez C, Bockaert J. Dynamic reorganization of the a strocyte actin cytoskeleton elicited by cAMP and PACAP: a role for phosphatidylinositol 3-kinase inhibition. European Journal of Neuroscience, 2005, 21(1): 26-32.
1. Schmidt W, Reymann KG. Preliferating cells differentiate into neurons in the hippocampal CA1 region of gerbils after global cerebral ischemic. Neurosci Lett, 2002, 334(3): 153-56.
2. Pcttigrew LC, Holtz ML, Graddack SD, et al. Microtubular proteolysis in focal cerebral ischemia. J Cereb Blood Flow Metab, 1996, 16(6): 1189-202.
3. Turker KL, Meyer M, Barde YA. Neurotrophins are required for nerve growth during development. Nature Neuroscience, 2001, 4(1): 29-37.
4. Benitez-King G, Ramires-Rodrigue G. The neuronal cytal cytoskeleton as a potential therapeutical target in neurodegenerative disease and schizophrenia. Current Drug Targets, 2004, 3(6): 515-33.
5. Yin HL, Stoll JT. Proteins that regulate dynamics actin remodeling in response to membrane signaling minireview series. J of Biol Chem, 1999, 274(46): 32529-30.
6. Cheryl L, Gantto, Barbara J. Local ERM activation and dynamic growth cones at Schwann cell tips implicated in efficient of nodes of Ranvier. The Journal of Cell Biology, 2003, 162(3): 489-98.
7. Kaverina Z, Krylyshkina O, Small JV. Microtubule targeting of substrate contacts promotes their relaxation and dissociation. 1999, 146(5): 1033-44.
8. Conpstom A, Zajicek J, Webb A, et al. Gral lineages and myeiinzation in the central neurons system. Anat, 1997: 161-200.
9. Pekny M, Johansson CB, Eliasson C, et al. Abnormal reaction to central nervous system injury in mice lacking glial fibrillary acidic ptotein and nimentin. Cell Biology, 1999, 145(3): 503-14.
10. Aspenstoom P, Fransson A, Saras J. Rho GTPases have diverse effects on the organization of the actin filament system. Biochem, 2004, 337: 327-37.
11. Takai Y, Sasaki T, Matozaki T. Small GTP-binding proteins. Physiol Rev, 2001, 81: 153-208.
12. Etienne-Mannevide S, HallA. Rho GTPases in cell biology. Nature, 2002, 420: 629-35.
13. Wherlock M, Mellor H. The Rho GTPase family: a Racs to Wrchs story. J of Cell Sci, 2002, 115: 239-40.
14. Nobes CD, Hall A. Rho, rac and cdc42 GTPases regulate the assembly of mulfimolecular focal complexes associated with actin stress fibers, lamellipodia and filopodia. Cell, 2001, 81: 53-62.
15. Wojciak-Stothard B, Tsang LY, Haworth SG. Rac and Rho play opposing roles in the regulation of hypoxia/reoxygenation-induced permeability changes in pulmonary artery endothelial cells. American Journal of Physiology, 2005, 288(14): 749-60.
16. Woolf CJ, Bloechlinger S. It takes more than two to Nogo. Science, 2002, 297(5584): 1132-34.
17. Huber AB, Schwab ME. Nogo-A, a potent inhibitor of neurite outgrowth and regeneration. Biol Chem, 2000, 381: 407-19.
18. He XL, Bazan JF, Mcdermott G, et al. Structure of the Nogo receptor ectodomain: a recognition module implicated in myelin inhibition, Neuron, 2003, 38: 177-85.
19. Niederost B, Oertle T, Fritsche J, et al. Nogo-A and myelin-associated glycoprotein mediate neurite growth inhibition by antagonistic regulation of RhoA and Racl. J of Neurosci, 2002, 22(23): 10368-76.
20. Thornberry NA, Lazebruk Y, NancyA, et al. Caspases: Enemies within. Science, 1998, 281(5381): 1312-1316.
21. Kothakota S, Azuma T, et al. Caspases-3-generated fragment of gelsolin: Effector of morphological change in apoptosis. Science, 1997, 278(5336): 294-298.
22. Rudel T, Bokoch GM, et al. Membrane and morphological changes in apoptotic cells regulated by caspase-mediated activation of PA. Science, 1997, 276(5318): 1571-1574.
23. Mashhna T, Naito M, Tsuruo T. Caspase-mediated cleavage of cytoskeletal actin plays a positive role in the process of morphological apoptosis. Oncogene, 1999, 18(15): 2423-1430.
24. Brancolini C, Lazarevic D, Rodriguez J, Schneider C. Dismantling cell-cell contacts during apoptosis is coupled to a caspase-dependent proteolysis cleavage of beta-catenin. Journal of Cell Biology, 1997, 139(3): 759-71.
25. Lee M, et al. Myelin-associated glycoprotein inhibits neurite/axon growth and causes growth cone collapse. J of Neurosci Res, 1996, 46: 404-14.
26. Bandtlow CE, Schmidt MF, et al. Role of intracellular calcium in NI-35-evoked collapse of neuronal growth cones. Science, 1993, 259: 80-83.
27. Sakamoto Y, Sakai O, et al. Involvement of calpain isoforms in ischemia-reperfusion injury in rat retina. Eye Res, 2000, 21: 571-80.
28. Tamada Y, Fukiage C, et al. Involvement of calpain in hypoxia-induced damage in rat retina in vitro. Comp Biochem Physiol, 2002, 131: 221-25.
29. Yoshiyuki T, Emi NA, et al. Proteolysis of neuronal cytoskeletal proteins vy calpain contributes to rat retina cell death induced by hypoxia. Brain Research, 2005, 1050: 148-55.
30. Kitagawa M, Matsumoto TC, Saido, et al. Species differences in fordrin proteolysis in the ischemic brain. J of Neuroscience Res, 1999, 55: 643-49.
31. Tokota M, Saido TC, et al. Calpain induces proteolysis of neuronal cytoskeleton in ischemic gerbil forebrain. Brain Res, 2003, 984: 122-32.
32. Kusakawa G, Saito T, et al. Calpain-dependant proteolysis cleavage of the p35 cyclin-dependant kinase 5 activator to p25. J of Bio Chem, 2000, 275: 17166-72.
33. Lee MS, Kwon Y, et al. Neurotoxicity induces cleavage of p35 to p25 by calpain. Nature, 2000, 405: 360-64.
34. Nath R, Davis M, et al. Processing of ckd5 activator p35 to its truncated form(p25) by calpain in acutely injury neuronal cell. Biochem Biophys Res, 2000, 274: 16-21.
35. Levy SN, KimchiA. Death associated protein(DAPs): From gene identification to the analysis of their apoptotic and tumor suppressive functions. Oncogene, 1998, 17(25): 3331-40.
36. Spillmann AA, Bandtlow CE, et al. Identification and characterization of a bovine neurite growth inhibitor(bNI-220). J of Biol Chem, 1998, 273: 19283-93.
37. Fiedler M, Horn C, et al. An engineered IN-1 Fab fragment with improved affinity for the Nogo-A axonal growth inhibitor permits immunochemical detection and shows enhanced neutralizing activity. Ptotein Engineering, 2002, 15(11): 941-41.
38. Fouad K, Dietz V, Schwab ME. Improving axonal growth and functional recovery after experimental spinal cord injury by neutralizing myelin associated inhibitors. Brain Res, 2001, 36(2-3): 204-12.
39. Kastin A J, Pan W. Targeting neurite growth inhibitors to induce CNS regeneration. Current Pharmaceutical Design, 2005, 11(10): 1247-53.
40. Grandpre T, Li S, Strittmatter SM. Nogo-66 receptor antagonist peptide promotes axonal regeneration. Nature, 2002, 417: 547-51.
41. Founder AE, Takizawa BT, Strittmatter SM. Rho kinase inhibition enhances axonal regeneration in the injured CNS. J of Neurosci, 2003, 23: 1416-23.
42. Hastie LE, Patton WF, Hechtman HB, et al. H2O2-induced filamin redistribution in endothelial cell is modulated by the cyclic AMP-dependant protein kinase pathway. J of Cell Physiol, 1997, 172(3): 373-81.
43. Jin Qiu, Dongming Cai, Haining Dai, et al. Spinal axon regeneration induced by elevation of cyclic AMP. Neuron, 2002, 34: 895-903.
44. Perez V, Bouschet T, Fernandez C, Bockaert J. Dynamic reorganization of the astrocyte actin cytoskeleton elicited by cAMP and PACAP : a role for phosphatidylinositol 3-kinase inhibition. European Journal of Neuroscience, 2005, 21(1): 26-32.
45. Soto I, Rosentha JJ, Blagburn JM, Blanco RE. Fibroblast growth factor 2 applied to the optic nerve after axotomy up-regulates BDNF and TrkB in ganglion cells by activation the ERK and PKA signaling pathways. Journal of Neurochemistry, 2006, 96(1): 82-96.
46. Dongming Cai, Kangwen Deng, Wilfredo M, et al. Arginase I and polyamines act downstream from cAMP in overcoming inhibition of axonal growth MAG and myelin in vitro. Neuron, 2002, 35: 711-19.
47. Inoue J, Nakamura M, Cui YS, et al. Structure-activity relationship study and drug profile of SJA6017 as a potent calpain inhibitor. J of Med Chem, 2003,46:868-871.
48. Chatterjee PK, Todorovic Z, Sivarajah A, et al. Inhibition of calpain activation (PD150606 AND E-64) and renal ischemia-reperfusion injury. Biochemical Pharmacology, 2005, 69 (7): 1121-31.
49. Balsam LB, Kofidis T, Robbins RC. Caspase-3 inhibition preserves myocardial geometry and long-term function after infarction. Journal of Surgical Research, 2005, 124(2): 194-200.
2 Rice J, Vannucci R, Brierly J. The influence of immaturity on hypoxia-ischemic brain damage in the rat. Ann Neurol. 1981, 9: 131-141
3 Back SA, Han BH, Luo NL, et al. Selective vulnerability of late oligodendrocyte progenitors to hypoxia-ischemia. J Neurosci. 2002, 22(2): 455-463
4 Paxinos G, Waston C. The rat brain in stereotaxic coordinate. 3rd Edition. Academic Press, Sydney, 1998.
5 Chang YS, Mu DZ, Michael WE, et al. Erythropoietin improves functional and histological outcome in neonatal stroke. Pediatric Res, 2005, 58(1): 106-11
6 袁宝莉，李瑞林，等．新生大鼠脑白质损害模型的建立与评价．新生儿科杂志，2004，19(1)：17-19．
7 Back SA, Luo NL, Borenstein NS, et al. Late oligodendrocyte progenitors coincide with the development window of volunerability for human perinatal white matter injury. J of Neurosci, 2001, 21(4): 1302-12.
8 Cai Z, Pang Y, Xiao F, et al. Chronic ischemia preferentially causes white matter injury in the neonatal rat brain. Brain Res, 2001, 898: 126-35.
9 Kohlhauser C, Mosgoller W, Hoger H, et al. Myelination deficits in brain of rats following perinatal asphyxia. Life Sci, 2000, 67: 2355-68.
10 Redecker C, Hagemann G, Marret S, et al. Long-term evolution of excitotoxic cortical dysgenesis induced in the developing rat brain. Dev Brain Res, 1998, 109: 109-13.
11 Husson I, Mesples B, Bac P, et al. Melatoninergic neuroprotection of the murine periventricular white matter against neonatal excitotoxic challenge. Ann Neurol, 2002, 52: 82-92.
1 余波，姚裕家，等．缺血再灌注损伤对新生鼠肾小管上皮细胞F-actin的影响．上海第二医科大学学报．2004，24：365-70．
2 Aspenstoom P, Fransson A, Saras J. Rho GTPases have diverse effects on the organization of the actin filament system. Biochem, 2004, 337: 327-37.
3 Takai Y, Sasaki T, Motozaki T. Small GTP-binding proteins. Physiol REV, 2001, 81: 153-208.
4 Estienne-Mannevide S, Hall A. Rho GTPase in cell biology. Nature, 2002, 420: 629-35.
5 Wojciak-Stothard B, Tsang LY, Haworth SG. Rac and Rho play opposing roles in the regulation of hypoxia/reoxygenation-induced permeability changes in pulmonary artery endothelial cells. American Journal of Physiology, 2005, 288(14): 749-60.
6 Nobes CD, Hall A. Rho, rac and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia and filopodia. Cell, 2001, 81: 53-62.
7 王华，姚裕家，陈大鹏．缺氧缺血新生鼠脑组织Ng-R含量变化．四川医学，2005，26(4)：362-64．
8 Benitez-King G, Ramires-Rodrigue G. The neuronal cytal cytoskeleton as a potential therapeutical target in neurodegenerative disease and schizaphrenia. Current Drug Targets, 2004, 3(6): 515-33.
9 Niederost B, Oertle T, Fritsche J, etal. Nogo-A and myelin-associated glycoprotein mediate neurite growth inhibition by antagonistic regulation of RhoA and Racl. J of Neurosci, 2002, 22(23): 10368-76.
10 Yin HL, Stoil JT. Proteins that regulate dynamics actin remodeling. in response to membrane signaling minireview series. J of Biol Chem, 1999, 274(46): 32529-30.
11 Cheryl L, Gantto, Barbara J. Local ERM activation and dynamic growth cones at Schwann cell tips implicated in efficient of nodes of Ranvier. The Journal of Cell Biology, 2003, 162(3): 489-98.
12 Raman N, Atkinson SJ. Rho controls actin cytoskeletal assembly in renal epithelial cells during ATP depletion and recovery. American Journal of Physiology, 1999, 276(6): 1312-24.
13 Yoshiyuki T, Emi NA, et al. Proteolysis of neuronal cytoskeletal proteins by calpain contributes to rat retina cell death induced by hypopxia. Brain Research, 2005, 1050: 148-55.
14 Mashima T, Naito M, Tsuruo T. Caspase-mediated cleavage of eytoskeleton actin plays a positive role in the process of morphological apoptosis. Oncogene, 1999, 18(15): 2423-30.
1 Foumier AE, Taldzawa BT, Strittmatter SM. Rho kinase inhibiton enhances axonal regeneration in the injured CNS. J of Neurosci, 2003, 23: 1416-23.
2 Hastie LE, Patton WF, Hechtman HB, et al. H_2O_2 induced filamin redistribution in endothelia cell is modulated by the cyclic AMP-dependant protein kinase pathway. J of Cell Physiol, 1997, 172(3): 373-81.
3 Jin Qiu, Dongming Cai, Haining Dai, et al. Spinal axon regeneration indeced by elevation of cyclic AMP. Neuron, 2002, 34: 895-903.
4 Dongming Cai, Kangwen Deng, Wilfredo M, et al. Arginase Ⅰ and polyamines act downstream from cAMP in overcoming inhibition of axonal growth MAG and myelin in vitro. Neuron, 2002, 35: 711-19.
5 Soto I, Rosentha JJ, Blagbum JM, Blanco RE. Fibroblast growth factors 2 applied to the optic nerve after axotomy up-regulates BDNF and TrkB in ganglion cells by activation the ERK and PKA signaling pathways. Journal of Neurochemistry, 2006, 96(1): 82-96.
6 李良平，徐如祥，等．脑损伤后血脑屏障损害的信号传导机制研究．第一军医大学学报，2001，21(9)：659-61．
7 Perez V, Bouschet T, Fernandez C, Bockaert J. Dynamic reorganization of the a strocyte actin cytoskeleton elicited by cAMP and PACAP: a role for phosphatidylinositol 3-kinase inhibition. European Journal of Neuroscience, 2005, 21(1): 26-32.
1. Schmidt W, Reymann KG. Preliferating cells differentiate into neurons in the hippocampal CA1 region of gerbils after global cerebral ischemic. Neurosci Lett, 2002, 334(3): 153-56.
2. Pcttigrew LC, Holtz ML, Graddack SD, et al. Microtubular proteolysis in focal cerebral ischemia. J Cereb Blood Flow Metab, 1996, 16(6): 1189-202.
3. Turker KL, Meyer M, Barde YA. Neurotrophins are required for nerve growth during development. Nature Neuroscience, 2001, 4(1): 29-37.
4. Benitez-King G, Ramires-Rodrigue G. The neuronal cytal cytoskeleton as a potential therapeutical target in neurodegenerative disease and schizophrenia. Current Drug Targets, 2004, 3(6): 515-33.
5. Yin HL, Stoll JT. Proteins that regulate dynamics actin remodeling in response to membrane signaling minireview series. J of Biol Chem, 1999, 274(46): 32529-30.
6. Cheryl L, Gantto, Barbara J. Local ERM activation and dynamic growth cones at Schwann cell tips implicated in efficient of nodes of Ranvier. The Journal of Cell Biology, 2003, 162(3): 489-98.
7. Kaverina Z, Krylyshkina O, Small JV. Microtubule targeting of substrate contacts promotes their relaxation and dissociation. 1999, 146(5): 1033-44.
8. Conpstom A, Zajicek J, Webb A, et al. Gral lineages and myeiinzation in the central neurons system. Anat, 1997: 161-200.
9. Pekny M, Johansson CB, Eliasson C, et al. Abnormal reaction to central nervous system injury in mice lacking glial fibrillary acidic ptotein and nimentin. Cell Biology, 1999, 145(3): 503-14.
10. Aspenstoom P, Fransson A, Saras J. Rho GTPases have diverse effects on the organization of the actin filament system. Biochem, 2004, 337: 327-37.
11. Takai Y, Sasaki T, Matozaki T. Small GTP-binding proteins. Physiol Rev, 2001, 81: 153-208.
12. Etienne-Mannevide S, HallA. Rho GTPases in cell biology. Nature, 2002, 420: 629-35.
13. Wherlock M, Mellor H. The Rho GTPase family: a Racs to Wrchs story. J of Cell Sci, 2002, 115: 239-40.
14. Nobes CD, Hall A. Rho, rac and cdc42 GTPases regulate the assembly of mulfimolecular focal complexes associated with actin stress fibers, lamellipodia and filopodia. Cell, 2001, 81: 53-62.
15. Wojciak-Stothard B, Tsang LY, Haworth SG. Rac and Rho play opposing roles in the regulation of hypoxia/reoxygenation-induced permeability changes in pulmonary artery endothelial cells. American Journal of Physiology, 2005, 288(14): 749-60.
16. Woolf CJ, Bloechlinger S. It takes more than two to Nogo. Science, 2002, 297(5584): 1132-34.
17. Huber AB, Schwab ME. Nogo-A, a potent inhibitor of neurite outgrowth and regeneration. Biol Chem, 2000, 381: 407-19.
18. He XL, Bazan JF, Mcdermott G, et al. Structure of the Nogo receptor ectodomain: a recognition module implicated in myelin inhibition, Neuron, 2003, 38: 177-85.
19. Niederost B, Oertle T, Fritsche J, et al. Nogo-A and myelin-associated glycoprotein mediate neurite growth inhibition by antagonistic regulation of RhoA and Racl. J of Neurosci, 2002, 22(23): 10368-76.
20. Thornberry NA, Lazebruk Y, NancyA, et al. Caspases: Enemies within. Science, 1998, 281(5381): 1312-1316.
21. Kothakota S, Azuma T, et al. Caspases-3-generated fragment of gelsolin: Effector of morphological change in apoptosis. Science, 1997, 278(5336): 294-298.
22. Rudel T, Bokoch GM, et al. Membrane and morphological changes in apoptotic cells regulated by caspase-mediated activation of PA. Science, 1997, 276(5318): 1571-1574.
23. Mashhna T, Naito M, Tsuruo T. Caspase-mediated cleavage of cytoskeletal actin plays a positive role in the process of morphological apoptosis. Oncogene, 1999, 18(15): 2423-1430.
24. Brancolini C, Lazarevic D, Rodriguez J, Schneider C. Dismantling cell-cell contacts during apoptosis is coupled to a caspase-dependent proteolysis cleavage of beta-catenin. Journal of Cell Biology, 1997, 139(3): 759-71.
25. Lee M, et al. Myelin-associated glycoprotein inhibits neurite/axon growth and causes growth cone collapse. J of Neurosci Res, 1996, 46: 404-14.
26. Bandtlow CE, Schmidt MF, et al. Role of intracellular calcium in NI-35-evoked collapse of neuronal growth cones. Science, 1993, 259: 80-83.
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