抗肿瘤坏死因子-α单克隆抗体对大鼠脊髓损伤细胞凋亡的影响
摘要
TNF-α是各种炎症和免疫反应中由多种细胞分泌的一类多向性细胞因子。作为一种炎症细胞因子,在脊髓损伤的急性期,TNF-α有促进细胞凋亡作用,在慢性期还具有诱导小胶质细胞及星形细胞增殖及聚集的作用。本实验旨在通过应用Allen’s改良法复制大鼠SCI模型,同时局部应用抗TNF-α单克隆抗体(Anti - TNF–αmAb)治疗,从形态学角度、细胞因子表达以及凋亡信号转导通路角度观察抗TNF-α单克隆抗体治疗对大鼠SCI发生及愈后的影响,并对其机制作深入探讨,得到如下结论:1.细胞凋亡是SCI早期主要的生物学事件;2.细胞凋亡的调控基因家族bax/bcl-2通过调节细胞凋亡参与SCI的发生发展;3. TNF-α在SCI发生发展中起重要作用,尤其是在调节细胞凋亡信号通路中起重要作用;4.在SCI损伤部位局部应用抗TNF-α特异性抗体,可延缓或抑制SCI的发生发展,其机制主要通过调节bcl-2、bax基因及蛋白表达,使二者表达量比值改变,并可调节IL-6、IL-8等多种炎症相关因子含量,从而实现对SCI的治疗作用。本研究结果可为临床急性脊髓损伤的治疗提供新的思路和方法。
It is a worldwide subject for therapy of spinal cord injury (SCI). Although there have been taken amazing outcome on gene therapy of SCI in experiment study,for the complex effect factor and injury mechanism,there is still a lot of key point unknown for people to study incontinuous.TNF-αis a cytokine of inflammation, which can be released from neuron and others.In this research, we will detect the protection role of monoclone TNF-αAntibody in spinal cord injury.
In this research, the BBB achievement of the SCI group and TNF-αtreated group were lower than that of the sham group at after 12 h, 1 d after SCI.the BBB achievement of the SCI group and TNF-αtreated group were lower than that of the sham group at 3 d, 7 d, and 14 d after SCI,While at 7 d after SCI, compared with sham group, the BBB of TNF-αtreated group was higher significantly than that of SCI group( P < 0.05).While at 14 d after SCI, compared with SCI group, the BBB of TNF-αtreated group was higher significantly than that of SCI group( P < 0.05).
Histology detection found that morphorlogy of spinal cord nerve cell of the sham group was normal. spinal cord nerve cell edema can be seen, but no apoptosis can be seen at 12h after SCI,inflamatory cell infiltration can be seen in spinal cord tissue at 3d after SCI,repair change can be seen in spinal cord tissue at 7d after SCI,scar formation can be seen in injured spinal cord tissue at 14d after SCI,while at 7d after anti- TNF-αtreatment,nerve cell morphology begin to repair, and function of spinal cord. at 14d after anti- TNF-αtreatment, spinal cord tissue structure arrange regular, inflammatory cell disappear.
The immunochemistry results of Image analysis of bcl-2 and bax showed that the index of bcl-2/bax of SCI group decresed significantly at 12 h after SCI, compared with the shamI group, P<0.05. which increase gradually.While at 12h、1d、3d、7d after anti-TNF-αtreatment, the index of bcl-2/bax of TNF-αtreated group increased significantly, compared with SCI group, P<0.05.
The RT-PCR results show that bcl-2 mRNA expression level of SCI group increase at 12h after SCI, reach the peak walue at 24h after SCI, compared with sham group, P<0.05. then which decrease gradually, but which is higher compared with sham group, P<0.05. After treated with anti-TNF-αantibody, the bcl-2 mRNA expression of TNF-αtreated group was higher significantly than that of SCI group(P<0.05)at12 h、1d、3d、7d after SCI.the bax mRNA expression was increasing and reach the peak value at 12h after SCI, compared with sham group, P<0.05.and then decreased.the bax mRNA expression of SCI group was higher significantly than that of sham group(P<0.05)at 1d、3d、7d after SCI.while anti-TNF-αtreated was applied, bax mRNA expression of TNF-αtreated group was no significantly difference from that of SCI group at each time point. (P﹥0.05)
Western blot results show that,the bcl-2 protein expression was increasing at 12 h after SCI and reach the peak value at 24h after SCI, and then decreased. compared with sham group, P<0.05.While anti-TNF-αtreated was applied, bcl-2 protein expression of TNF-αtreated group was significantly higher than that of SCI group, compared with SCI group at each time point., P<0.05.bax protein expression of SCI group was at the peak value at 12h after SCI, and decreased furtherly at 1d、3d and 7d after SCI, compared with sham group, P<0.05.After treated with anti-TNF-αantibody, the bax protein expression of TNF-αtreated group was no significantly difference from that of SCI group at each time point. (P﹥0.05)
ELISA analysis found that
at 12 h after SCI, amount of IL-6 and IL-8 expression was at the peak value, compared with the sham group, P<0.05.with times go on, the amount of IL-6 and IL-8 expression were lower grandually than that of SCI group, and at 14 d after SCI, the amount of IL-6 and IL-8 expression were access to the normal level.While after anti-TNF-αtreatment was applied, IL-6 and IL-8 expression of TNF-αtreated group decreased significantly, compared with SCI group, P<0.05.
TUNEL detection was applied to evaluate the apoptosis in the SCI rats. It was found that the apotosis cell can be seen clearly 3 days after SCI, which can be prevented after treatment of anti-TNF-α.
From our research, we can get these conclusions:1. apoptosis is an important event of SCI; 2. Bax/bcl-2 family take part in the development of SCI through control the processof apoptosis; 3. TNF-αplay an important role in SCI, especially in regulating signal transduction pathway of apoptosis; 4. Anti-TNF-αtreatment by monoclone antibody can regulate the expression of IL-6、IL-8 and bcl-2,inhibit the process of apotosis after SCI in rats.
It is a worldwide subject for therapy of spinal cord injury (SCI). Although there have been taken amazing outcome on gene therapy of SCI in experiment study,for the complex effect factor and injury mechanism,there is still a lot of key point unknown for people to study incontinuous.TNF-αis a cytokine of inflammation, which can be released from neuron and others.In this research, we will detect the protection role of monoclone TNF-αAntibody in spinal cord injury.
In this research, the BBB achievement of the SCI group and TNF-αtreated group were lower than that of the sham group at after 12 h, 1 d after SCI.the BBB achievement of the SCI group and TNF-αtreated group were lower than that of the sham group at 3 d, 7 d, and 14 d after SCI,While at 7 d after SCI, compared with sham group, the BBB of TNF-αtreated group was higher significantly than that of SCI group( P < 0.05).While at 14 d after SCI, compared with SCI group, the BBB of TNF-αtreated group was higher significantly than that of SCI group( P < 0.05).
Histology detection found that morphorlogy of spinal cord nerve cell of the sham group was normal. spinal cord nerve cell edema can be seen, but no apoptosis can be seen at 12h after SCI,inflamatory cell infiltration can be seen in spinal cord tissue at 3d after SCI,repair change can be seen in spinal cord tissue at 7d after SCI,scar formation can be seen in injured spinal cord tissue at 14d after SCI,while at 7d after anti- TNF-αtreatment,nerve cell morphology begin to repair, and function of spinal cord. at 14d after anti- TNF-αtreatment, spinal cord tissue structure arrange regular, inflammatory cell disappear.
The immunochemistry results of Image analysis of bcl-2 and bax showed that the index of bcl-2/bax of SCI group decresed significantly at 12 h after SCI, compared with the shamI group, P<0.05. which increase gradually.While at 12h、1d、3d、7d after anti-TNF-αtreatment, the index of bcl-2/bax of TNF-αtreated group increased significantly, compared with SCI group, P<0.05.
The RT-PCR results show that bcl-2 mRNA expression level of SCI group increase at 12h after SCI, reach the peak walue at 24h after SCI, compared with sham group, P<0.05. then which decrease gradually, but which is higher compared with sham group, P<0.05. After treated with anti-TNF-αantibody, the bcl-2 mRNA expression of TNF-αtreated group was higher significantly than that of SCI group(P<0.05)at12 h、1d、3d、7d after SCI.the bax mRNA expression was increasing and reach the peak value at 12h after SCI, compared with sham group, P<0.05.and then decreased.the bax mRNA expression of SCI group was higher significantly than that of sham group(P<0.05)at 1d、3d、7d after SCI.while anti-TNF-αtreated was applied, bax mRNA expression of TNF-αtreated group was no significantly difference from that of SCI group at each time point. (P﹥0.05)
Western blot results show that,the bcl-2 protein expression was increasing at 12 h after SCI and reach the peak value at 24h after SCI, and then decreased. compared with sham group, P<0.05.While anti-TNF-αtreated was applied, bcl-2 protein expression of TNF-αtreated group was significantly higher than that of SCI group, compared with SCI group at each time point., P<0.05.bax protein expression of SCI group was at the peak value at 12h after SCI, and decreased furtherly at 1d、3d and 7d after SCI, compared with sham group, P<0.05.After treated with anti-TNF-αantibody, the bax protein expression of TNF-αtreated group was no significantly difference from that of SCI group at each time point. (P﹥0.05)
ELISA analysis found that
at 12 h after SCI, amount of IL-6 and IL-8 expression was at the peak value, compared with the sham group, P<0.05.with times go on, the amount of IL-6 and IL-8 expression were lower grandually than that of SCI group, and at 14 d after SCI, the amount of IL-6 and IL-8 expression were access to the normal level.While after anti-TNF-αtreatment was applied, IL-6 and IL-8 expression of TNF-αtreated group decreased significantly, compared with SCI group, P<0.05.
TUNEL detection was applied to evaluate the apoptosis in the SCI rats. It was found that the apotosis cell can be seen clearly 3 days after SCI, which can be prevented after treatment of anti-TNF-α.
From our research, we can get these conclusions:1. apoptosis is an important event of SCI; 2. Bax/bcl-2 family take part in the development of SCI through control the processof apoptosis; 3. TNF-αplay an important role in SCI, especially in regulating signal transduction pathway of apoptosis; 4. Anti-TNF-αtreatment by monoclone antibody can regulate the expression of IL-6、IL-8 and bcl-2,inhibit the process of apotosis after SCI in rats.
引文
[1]Ropper AH. Traumatic injuries of the head and spine.In: Braunwald E, Fauci AS, Kasper DL, Hauser, SL, et al(Eds.). Harrison’s Principles of Internal Medicine, fifteenth ed. McGraw-Hill, New York, 2001, pp: 2441-2442.
[2]Tyor WR, Avgeropoulos N, Ohlandt G, et al. Treatment of spinal cord impact injury in the rat with transforming growth factorbeta. J Neurol Sci, 2002, 200: 33-41.
[3]Beattie MS, Hermann GE, Rogers RC, et al. Cell death in models of spinal cord injury. Prog Brain Res, 2002, 137: 37-47.
[4]Blight AR, Leroy EC Jr, Heyes MP. Quinolinic acid accumulation in injured spinal cord: time course, distribution, and species differences between rat and guinea pig. J Neurotrauma. 1997; 14: 89-98.
[5]Schwartz M, Hauben ET. cell-based therapeutic vaccination for spinal cord injury. Prog.Brain Res, 2002, 137: 401-406.
[6]Young W. Spinal cord contusion models. Prog Brain Res, 2002, 137: 231-255.
[7]Lee M, Lee ES, Kim YS, et al. Ischemic injury-specific gene expression in the rat spinal cord injury model using hypoxia-inducible system. Spine, 2005, 30: 2729-2734.
[8]Balentine JD.Pathology of experimental spinal cord trauma:ultrastructure of axons and myelin. Lab Invest, 1978, 39: 254-266.
[9]Wagner F, Dhormann G, Bucy P. Histopathology of transitory traumatic paraplegia in the monkey. J Neurosurg, 1971, 35:272-276.
[10]Lee M, Lee ES, Kim YS, et al. Epidemiology, demographics, and pathophysiology of acute spinal cord injury. Spine, 2001, 26: S2-S12.
[11]Sekhon LH, Fehlings MG. Carlson GD, et al. Sustained spinal cord compression: part 1: time-dependent effect on long-tern pathophysiology. Bone Joint Surg Am, 2003, 85-A: 86-94.
[12]吴昊天,张英泽,李增炎,等.持续脊髓压迫与神经功能恢复的相关性研究.中国康复医学杂志, 2004, 19: 657-660.
[13]初同伟,吴梅英,马树支,等.不完全性急性脊髓损伤后脊髓病理改变、脊髓灰质血流量和运动诱发电位变化的实验研究.第三军医大学学报, 2000, 22: 750-753.
[14]Park E, Velumian AA, Fehlings G. The role of excitotoxicity in secondary mechanisms of spinal cord injury: a review with an emphasis on the implications for white matter degeneration. Neurotrauma, 2004, 21: 7540-7774.
[15]Akdemir H, Pasaoglu A. Histopathology of experimental spinal cord trauma. Comparison of treatment with TRH, naloxone, and dexamethasone.Res Exp Med (Berl), 1992, 192: 177-183.
[16]Tator CH, Koyanagi I. Vascular mechanisms in the pathophysiology of human spinal cord injury. J Neurosurg, 1997, 86: 483-492.
[17]Koyanagi I, Tator CH, Lea PJ. Three-dimensional analysis of the vascular system in the rat. Spinal cord with scanning electron microscopy of vascular corrosion casts. part2. acute spinal cord injury. Neurosurg, 1993, 33: 285-290.
[18]Koyanagi I, Tator CH, Theriault E. Silicone rubber microangiography of acute spinal cord injury in the rat. Neurosurg, 1993, 33: 285-290.
[19]Salzman SK, Acosta R, Beck G, et al. Spinal endothel contentis elevated moderate local trauma in the rat to levels associated with locomotor dysfunction after intrathecal injection. J Neurotrama, 1996, 13(2): 93-10.
[20]McKenzie-AL. Immunolocalization of endothelin in the traumatized spinal cord: relationship to blood-spinal cord barrier breakdown. J Neurotrauma, 1995, 12: 257.
[21]Yong W. Stratategies for the development of new and better pharma cological treatments for acute spinal cord injury. Adv Neurol, 1993, 59: 249
[22]Hall ED, Wolf DL, Braughler JM. Effects of a single large dose of methylprenisolone sodium succincton experimental post traumatic spinal cord schema: Dose response and time action analysis. J Neurosurg, 1984, 61: 124-130.
[23]Floyd RA, Waston JJ, Wong PK. Sensitive assay of hydroxy1free radical formation utilizing high pressure liquid chromatography with electrochemical detection of phenol and salicylate hydroxylation products. J Biochem Biophys Methods, 1984, 10: 221.
[24]Culmsee, C. Gerling, N. Landshamer, S. et al. Nitric oxide donors induce neurotrophin-like survival signaling and protect neurons against apoptosis. Mol. Pharmacol. 2005, 68: 1006-1017.
[25]Wu W. Neurol nitricoxide synthaseis induced in spinal neurons by traumatic injury. Neurosience, 1994, 61: 719
[26]Emery E, Aldana P, Bunge MB, et al. Apoptosis after traumatic human cord injury. Neurosurg, 2004, 89: 911-920.
[27]Matsushita Y, Shima K, Nawashiro H, et al. Real time monitoring of glutamate following fluid percussion brian injury with hypox in the rat. J Neurotrauma, 2000, 17: 143-153
[28]Krenz NR, Weaver LG.. Effect of spinal cord transtection on N Methyl aspartate receptors in the cord. J Neurotrauma, 1998, 15: 1027-1036
[29]Wrathall JR, Choiniere D, Teng YD. Dose deoendent reduction of tissue loss and functional impairment after spinal cord trauma with the AMPA/kainite antagonist NBQX. Neurosic, 1994, 14: 6598-6607
[30]Gaviria M, Privat A, Arbigny P, et al. Neuroprotective effects of gacyclidinea after experimental photochenmical spinal coed lesion in adult rats: dose window and time window effects. J Neurotrauma, 2000, 1719-173.
[31]Blomgren K, Mcrae A, Elmered A, et al.The calpainproteolytic system in neonatal hypoxic-isxhemia. Ann N Y Acad Sic, 1997, 825: 104-119
[32]Dinsmore JH, Solomon F. Inhibition of MAP-2ex-pression affects both morphological and cell divisionphenotypes of neuronal differentiation. Cell, 1991, 64(4): 817-826
[33]Chen J, Kanai Y, Cowan NJ, et al. Projection domainsof MAP-2and tau determine spacings between mir-crotubules in dendrites and axons. Nature, 1992, 360: 674-677
[34]Nunez J. Immature and mature variants of MAP-2 and tau propteins and neuronal plasticity. Trends Neurosci, 1988, 11: 477-479
[35]Yong J, Robak G, Liu D, et al. A sampling artifact inthe microdialysis study of changes in extracellular[Mg2+] upon apinal cord injury. Anal Biochem, 1997, 245: 203-206
[36]Balentine JD. Pathology of experimental spinal cordtrauma: The necrotic lesion as a function of vascularinjury. Lab Invest, 1978, 39: 236-253
[37]Das OK. Cellular biochemical and molecular aspectsof reperfusion on injury. Ann N Y Acad Sci, 1994, 723: 1-5
[38]Le YL, Shih K, Bao P, et al. Cytokine chemokine ex-pression in contusedrat spinal cord.NeurochemInt, 2000, 36: 417-425
[39]McTigue DM, Tani M, Krivacic K, et al. Selectivechemokine mRNA accumulation in the rat spinalcord after contusion injury. Neurosci Res, 1998, 53: 368-376
[40]Le YL, Shih K, Bao P, et al. Cytokine chemokine expression in contused rat spinal. Neurochem Int, 2000, 36: 417-425
[41]Growe MJ, Bresnahan JC, Shuman SL, et al. Apoptosis and delayed degeneration after spinal cord injuryin rats and monkey. Nature Medicine, 1997, 3: 73-76
[42]Guilin LI, Gregor BR, Mohammad FA, et al. Apoptosis and expression of bcl-2 after compression trau-ma to rat spinal cord. J Neuropha Exp Neurol, 1996, 55: 281-289
[43]Liu XZ, Xu XM, Hu R, et al. Neuronal and glial ap-optsis after traumatic spinal cord injury. J Neu-rosci, 1997, 17: 5394- 5406
[44]Yong C, Arnold PM, Zoubine MN, et al. Apoptosiscellular compartments of rats spinal cord after severecontusion injury.J Neuro trauma, 1998, 15: 459-472
[45]Hansen-Algenstaedt N, Algenstaedt P, Schaefer C, et al. Neural drivenangiogenesis by overexpression of nerve growth factor. Histochem Cell Biol, 2006, 12: 637-649.
[46]Yong W. Stratategies for the development of newand better pharma cological treatments for acutespinal cord injury. Adv Neurol, 1993, 59: 249
[47]Barres BA, Jacobson MD, Schmid R. Dose oligodendrocyte survive depend on axons? . Curr Biol, 1993, 3: 489-497
[48]Dusart I, Schwad EM. Secondary cell death and in-flammatory reaction after dorsal henisction of the ratspinal cord. Eur J Neurosci, 1994, 6: 712-724
[49]Shuman SL, Bresnahan JC, Beattie MS. Apoptosis ofmicroglia and oligodendrocytes after spinal crod con-tusion in rats. J Neurosci Res, 1997, 50: 798-808
[50]Casha Re, Yu W, Fehlings MG. Oligodendroglialapoptosiss occurs along degeneration anons and andis associated with FAS and P75 expression following spinal cord injury. Neuroscience, 2001, 103: 203-218
[51]Zain J, Huang YQ, Feng X, et al. Concentration-de-pendent dual effect of thombin on impaired growth/apoptosis or mitogenes in tumor cells. Blood, 2000, 95:3133-3189.
[52]Donovan FM, Pike CJ, Cotnan CW, et al. Thrombininduces apoptosis in cultured neurons and astrocytesvia a pathway requiring tyrosine kinase and RhoAactivities. J Neurosci, 1997, 17: 5316-5326.
[53]Greenamyre JT, Porter RH. Anatomy and physiology of glutamate in the CNS. . Neurology, 1994, 44(11 Suppl): S7-S1.
[54]Lu, C. L. Liang, H. J. Chen, S. D. et al. Injury severity and cell death mechanisms: effects of concomitant hypovolemic hypotension on spinal cord ischemiareperfusion in rats. Exp Neurol, 2004, 185: 120-132.
[55]Lu P, Jones LL, Tuszynski MH. BDNF-expressing marrow stromal cellssupport extensive axonal growth at sites of spinal cord injury. ExpNeurol, 2005, 191: 344-360.
[56]Koda M, HashimotoM, Murakami M, et al. Adenovirus vector-mediatedin vivo gene transfer of brain-derived neurotrophicfactor(BDNF) promotes rubrospinal axonal regeneration and functional recovery aftercomplete transaction of the adult rat spinal cord. J Neurotrauma, 2004, 21: 329-337.
[57]Jean I, Lavialle C, Barthelaix-Pouplard A, et al. Neurotrophin-3 specif-ically increases mature oligodendrocyte population and enhances remy-elination after chemical demyelination of adult rat CNS. Brain Res, 2003, 972: 110-118.
[58]HaggT, Baker KA, Emsley JG, et al. Prolonged local neurotrophin-3infusion reduces ipsilateral collateral sprouting of spared corticospinalaxons in adult rats. Neuroscience, 2005, 130: 875-887.
[59]Schreyer DJ, Skene JH. Injury-associated induction of GAP-43 expression displays axon branch specificity in rat dorsal root ganglion neurons. J Neurobiol, 1993, 24: 959-970.
[60]Kwon BK, Tetzlaff W. Spinal cord regeneration: from gene to transplants. Spine, 2001; 26(24 supp1): s13-s22.
[61]Herdegen T, Skene P, Bahr M. The c-Jun transcription factor--bipotential mediator of neuronal death, survival and regeneration. Trends Neurosci, l997; 20: 227-23l.
[62]Fernandes KH, Fan DP, Tsui BJ, et a1. Influence of the axotomy to cell body distance in rat rubrospinal and spinal motoneurons: differential regulation ofGAP-43, tubulins, and neurofilament-M. J Comp Neurol, l999; 4l4: 495-5l0.
[63]Frey K, Laux T, Xu L, et a1. Shared and unique roles of CAP23 and GAP43 in actin regulation, neurite outgrowth, and anatomical plasticity. J Cell Biol, 2000; 149: 1443- l454.
[64]Uchida K, Baba H, Maezawa Y, et a1. Progressive changes in neurofilament proteins and growth-associated protein-43 immunoreactivities at the site of cervical spinal cord compression in spinal hyperostotic mice. Spine, 2002, 27: 480- 486.
[65]Becker T, Bernhardt RR, Reinhard E, et al. Readiness of zebrafish brain neurons to regenerate a spinal axon correlates with differential expression of specific cell recognition molecules. J Neurosci, l998; l8: 5789-5803.
[66]Jung M, Petrausch B, Stuermer CA. Axon-regenerating retinal ganglion cells in adult rats synthesize the cell adhesion molecule L1 but not TAG-1 or SC-1. Mol Cell Neurosci, l997; 9: 116-l3l.
[67]Woolhead CL, Zhang Y, Lieberman AR, et a1. Differential effects of autologous peripheral nerve grafts to the corpus striatum of adult rats on the regeneration of axons of striatal and nigral neurons and on the expression of GAP-43 and the cell adhesion molecules N-CAM and L1. J Comp Neurol, l998, 39l: 259-273.
[68]Brosamle C, Huber AB, Fiedler M, et a1. Regeneration of lesioned corticospinal tract fibers in the adult rat induced by a recombinant, humanized IN-1 antibody fragment. J Neurosci, 2000, 20: 8061-8068.
[69]Fitch MT, Silver J. Activated macrophages and the blood-brain barrier: inflammation after CNS injury leads to increases in putative inhibitory molecules. Cell Tissue Ras. 1997, 290: 379-384.
[70]Faweett JW, Asher RA. The glial scar and central nervous system repair. Brain Ras Bull, l999, 49 :377-391
[71]Stichel CC, Hermanns S, Luhmann HJ. et al. Inhibition of collagen IV deposition promotes regeneration of injured CNS axons. Eur J Neurosci, l999, 11: 632-646.
[72]Barinaga M. New view of spinal cord injury. Science, 1996, 274: 1466
[73]崔志明,倪斌,蔡卫华,等.兔慢性颈脊髓压迫减压术后凋亡基因bo1-2和bax的表达.中国临床康复, 2004, 8: 7164-7165.
[74]傅强,侯铁胜,鲁凯伍,等.大鼠脊髓急性损伤后神经细胞凋亡及相关基因表达.中国脊柱脊髓杂志. 2001. 1l: 92-94.
[75]Polyak K, Xia Y, Zweier JL, et al. A model for p53-induced apoptosis. Nature. 1997, 389: 300-305.
[76]Ramer MS, Priestley JV, McMahon SB. Functional regeneration of sensory axons into the adult spinal cord. Nature, 2000, 403: 312-316.
[77]Philips MF, Mattiasson G, Wieloch T, et al. Neuroprotective and behavioral efficacy of nerve growth factor-transfected hippocampal progenitor cell transplants after experimental traumatic brain injury. J Neurosurg, 200l: 94: 765-774.
[78]McKerracher L, David S, Jackson DL, et al. Identification of myelin-associated glycoprotein as a major myelin-drived inhibitor of neurite growth.Neuron. l994, l3: 805-811.
[79]Mukhopadhyay G, Doherty P, Walsh FS, et a1. A novel role of myelin-associated glycoprotein as an inhibitor of axonal regeneration. Neuron, l994: l3: 757-767.
[80]Reynolds BA, Weiss S. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science, 1992, 255: 1707–1710.
[81]Caroni P, Schwab ME. Two membrane protein fractions from rat central myelin with inhibitory properties for neurite growth and fibroblast spreading. J Cell Biol. l988: l06: l28l-1288
[82]Fournier AE, GrandPre T, Strittmatter SM. Identification of a receptor mediating Nogo-66 inhibition of axona1 regeneration. Nature, 200l: 409: 34l-346.
[83]Liu BP, Fournier A, GrandPre T. et al. Myelin-associated glycoprotein as a functional ligand for the Nogo-66 receptor. Scieetce, 2002, 297: 1190-1193.
[84]Merkler D, Metz GA, Raineteau O, et a1.Locomotor reeovery in spinal cord injury rats treated with an antibody neutralizing the myelin-associated neurite growth inhibitor Nogo-A. J Neurosci, 200l, 21: 3665-3673.
[85]Li S, Strittmatter SM. Delayed systemic Nogo-66 receptor antagonist promotes recovery from spinal cord injury. J Neurosci, 2003, 23: 4219-4227.
[86]Tang X, Davies JE, Davies SJ. Changes in distilbution,cell associations, and protein expression 1evels of NG2, neurocan ,phosphacan,brevican, versican V2, and tenascin-C during acute to chronic maturation of spinal cord scar tissue. JNeurosci Res, 2003, 71: 427-444
[87]Davies SJ, Goucher DR, Doller C, et a1. Robust regeneration of aduh sensory axons in degenerating white matter of the adult rat spinal cord.J Neurosci, l999, l9: 58l0-5822.
[88]Bradburv EJ, Moon LD, Popat RJ, el al. Chondroitinase ABC promotes functional recovery after spinal cord injury. Nature, 2002: 416: 636-640
[89]Moon LD, Asher RA, Fawcett JW, et al. Limited growth of severed CNS axons after treatment of adult rat brain with hyaluronidase. J Neurosci Res, 2003, 7l: 23-37.
[90]Azanchi R, Eternal G, Gupta R, et a1.Combined demyelination plus Schwann cell transplan tation therapy increases spread of cells and axonal regeneration following contusion injury. Neurotrauma, 2004, 21: 775-788.
[91]Joosten EA, Houweling DA. Local acute application of BDNF in the lesioned spinal cord and inflammatory and an tioxidant effects. Neu- roreport, 20o4, 15: 1163-1166.
[92]Takami T. Schwann cell but not olfactory ensheathing glia transplants improve hindlimb locomotor performance in the moderately contused adult rat thoracic spinal cord. J. Neurosci, 2002, 22: 6670–6681.
[93]Chen A, Xu XM, Kleitman N, et al. Methylprednisolone administration improves axonal regeneration into Schwann cell grafts in transected adult rat thoracic spinal cord. Exp. Neurol, 1996, 138: 261–276.
[94]Xu XM, Guenard V, KleitmanN, et a1. A combination of BDNF and NT-3 promotes supraspinal axonal regeneration into Schwann cell grafts in adult rat thoracic spinal cord. Exp Neurol, 1995, 134: 261 - 272
[95]Barakat DJ, Gaglani SM, Neravetla SR, et a1. Survival,integration, and axon growth suppo rt of gila transplanted into the chronically con·tused spinal cord.Cell Transplant, 2005, 14: 225-240.
[96]HIll CE, Moon LD, Weed PM, et a1. Labeled Schwann cell tcal-plantation: cell loss, host Schwann cell replacement, and strategies to enhance surviva1. Glia, 2006, 53: 338-343
[97]Ramon-Cueto A, Plant G.W, Avila J,et al. Long-distance axonal regeneration in the transected adult rat spinal cord is promoted by olfactory ensheathing glia transplants. J Neurosci, 1998, 18: 3803-3815.
[98]Guest JD. The ability of cultured human Schwann cells within PAN/PVC guidance channels to support regeneration in the transected nude rat spinal cord. Can. J Neurol Sci, 1996, 23: S1–S2.
[99]Li Y, Field P M, Raisman G.. Repair of adult rat corticospinal tract by transplants of olfactory ensheathing cells. Science, 1997, 277: 2000–2002.
[100]Bianco JI., Perry C, Harkin DG., et al. Neurotrophin 3 promotes purification and proliferation of olfactory ensheathing cells from human nose. Glia, 2004, 45: 111–123.
[101]Kato T, Honmou O, Uede T, et al. Transplantation of human olfactory ensheathing cells elicits remyelination of demyelinated rat spinal cord. Glia, 2000, 30: 209–218.
[102]Barnett SC. Identification of a human olfactory ensheathing cell that can effect transplant-mediated remyelination of demyelinated CNS axons. Brain, 2000, 123: 1581–1588.
[103]Guest J, Herrera LP, Qian T. Rapid recovery of segmental neurological function in a tetraplegic patient following transplantation of fetal olfactory bulb-derived cells. Spinal Cord, 2006, 44: 135–142.
[104]Huang, H. Influence of patients’age on functional recovery after transplantation of olfactory ensheathing cells into injured spinal cord injury. Chin Med J (Engl.), 2003, 116: 1488–1491.
[105]Dobkin BH, Curt A, Guest J. Cellular transplants in China: observational study from the largest human experiment in chronic spinal cord injury. Neurorehabil. Neural Repair, 2006, 20: 5–13.
[106]Jang JE, Shaw K, Yu XJ,et a1.Specific and stable gene transfer to human embryonic stem cells using pseudotyped lentiviral veclors.Stem Cells Dev, 2006, 15: 109-117.
[107]McDonald JW. Transplanted embryonic stem cells survive, differentiate and promote recovery in injured spinal cord. Nature Med., 1999, 5: 1410–1412.
[108]Harper JM. Axonal growth of embryonic stem cell-derived motoneurons in vitro and in motoneuron-injured adult rats. PNAS, 2004, 101: 7123–7128.
[109]Gage FH. Mammalian neural stem cells. Science, 2000, 287: 1433- 1441.
[110]王岩峰,吕刚,李花,等.神经干细胞移植对大鼠脊髓损伤后BDNF- GAP-43 (GAP-43)基因表达的影响.中华矫形外科杂志, 2004, 12: 1870-1872.
[111]Tnda H, Takahushi J, Mizoguchi A, et a1. Neurons generated from adalt rat hippocampal stem cells from functional glutama-rgic and GABAergic synapses in vitro. Exp Nerol, 2000, 165: 66-76
[112]Nakamura M, Toyama Y, Okano H. Transplantation of neural stem cells for spinal cord injury. Rinsho Shinkeigaku, 2005, 45: 874 - 876
[113]James AT, Joseph IE, Sander SS, et al. Embryonic Stem Cell Lines Derived from Human Blastocysts. Science, 1998, 282: 1145-1147.
[114]Fred HG, Inder MV. Stem cells at the dawn of the 21st century. PNAS, 2003, 100: 11817-11818.
[115]Kawaguchi S, lseda T, Nishio T. Effects of an embryonic repair graft on recovery from spinal cord injury. Prog Brain Res, 2004, 144: 155– 162.
[116]Peterson CA, Murphy RJ, Dupont-Versteegden EE, et a1. Cycling exercise and fetal spinal cord transplantation act synergistically on atro- phied muscle following chronic spinal cord injury in rats. Neurorehabil Neural Repair, 2000, 14: 85-91
[117]Cao Q, Benton RL, Whittemore SR. Stem cell repair of central nervous system injury. J. Neurosci Res, 2002, 68: 501–510.
[118]Daniel RM, Richard LG, David G. Stem Cell Biology. Copyright by Cold Spring Harbor Laboratory Press, Cold Spring Laboratory, New York. 2001: 10.
[119]Herrera J. Embryonic-derived glial-restricted precursor cells (GRP cells) can differentiate into astrocytes and oligodendrocytes in vivo. Exp. Neurol, 2001, 171: 11–21.
[120]Hill CE. Acute transplantation of glial-restricted precursor cells into spinal cord contusion injuries: survival, differentiation, and effects on lesion environment and axonal regeneration. Exp. Neurol., 2004, 190: 289–310.
[121]Gerald D. F, Ruth LF. Stem cells: science, policy, and ethics. J Clinical Investi, 2004, 114: 1364-1370.
[122]Schultz SS. Adult stem cell application in spinal cord injury. Curr Drug Targets, 2005, 6: 63–73.
[123]Koshizuka S, Okada S, Okawa A, et al. Transplanted hematopoietic stem cells from bone marrow differentiate into neural lineage cells and promote functional recovery after spinal cord injury in mice. J. Neuropathol. Exp. Neurol, 2004, 63: 64–72.
[124]Koda M, Okada S, Nakayama T, et al. Hematopoietic stem cell and marrow stromal cell for spinal cord injury in mice. Neuroreport, 2005, 16: 1763–1767.
[125]Ankeny DP, Mctigue DM, Jakeman LB, et a1. Bone marrow transplants provide tissue protection and directional guidance for axons after contusive spinal cord iury in rats. Exp Neurol, 2004, 190: 17– 31.
[126]Li Y, Chen J, WangL, et a1.Treatment of stroke in rat with intracarotid administration of marrow stromal cells. Neurology, 2001, 56: 1666-1672.
[127]Mahmood A, Lu D, Wang L, et a1. Intracerebral transplantation of n-ITOw stromal cells cultured with neurotrophic factors promotes functional recovery in adult rats subjected to traumatic brain injury. Neurotrauma, 2002, 19: 1609-1617.
[128]Chen X, Katakowski M, Li Y, et a1. Human bone nlarrow stromal cell cultures conditioned by traumatic brain tissue extracts:growth factor production. Neurosci Res, 2002, 69: 687-691
[129]Satake K, Lou J, Lenke LG. Migration of mesenchymal stem cells through cerebrospinal fluid into injury spinal cord tissue. Spine, 2004, 29(18): 1971-1979.
[130]lnoue M, Honmou O, Oka S, et a1. Comparative analysis of cemyelinating potential of focal an d intravenous administration of autologons bone nlarrow cells into the rat demyelinated spinal cord. Gila, 2003, 44: 111-118.
[131]Byung H, Yoon H, Cheol-Hee A, et al. A hypoxia-inducible gene expression system using erythropoietin 3 untranslated region for the gene therapy of rat spinal cord injury. Neuroscience Letters, 2007, 412: 118-122.
[132]Piantino J, Burdick JA, Goldberg D, et al. An injectable,biodegradable hydrogel for trophic factor delivery enhances axonal rewiring and improves performance after spinal cord injury. Exp Neurol, 2006, 23: 245-251.
[133]Shumsky JS, Tobias CA, Tumolo M, et al. Delayed transplantation of fibroblasts genetically modified to secrete BDNF and NT-3 into a spinal cord injury site is associated with limited recovery of function. Exp Neurol, 2003, 184: 114-130.
[134]McTigue DM, Horner PJ, Strokes BT, et al. Neurotrophin-3 and neurotrophic factors induce oligodendrocyte prolifiration and myelination ofregenerating axons in the contused adult rat spinal cord. Neurosci, 1998, 18: 5354-5365.
[135]Spenger C, Hyman C, Studer L, et al. Efects of BDNF on dopaminergic, serotonergic, and GABA ergic neurons in cultures of human fetal ventral mesencephalon. . Exp Neurol, 1995, 133: 50-63
[136]Jakeman LB, Wei P, Guan Z, et al. Related articles brain-derived neurotrophic factor stimulates hindlimb stepping and sprouting of cholinergic fibers after spinal cord injury. . Exp Neurol, 1998, 154: 170-184.
[137]Hains BC, Fullwood SD, Eaton J. Subdural engraftment of serotonergic neurons folowing spinal hemisection restores spinal serotonin, downregulates serotonin transporter, and increases BDNF tissue content in rat. Brain .Research, 2001, 913: 35-46.
[138]Vavrek R, Girgis J, Tetzlaff W, et al. BDNF promotes connections of corticospinal neurons onto spared descending interneurons in spinal cord injured rats. Brain, 2006, 129(Pt. 6): 1534-1545.
[139]Taylor SJ, Rosenzweig ES, McDonald JW, et al. Delivery of neurotrophin-3 from fibrin enhances neuronal fiber sprouting after spinal cord injury, Control. Release, 2006, 113226-235.
[140]Effect of controlled delivery of neurotrophin-3 from fibrin on spinal cord injury in a long term model Sara. Taylor a, Shelly E. J Control Release, 2006, 116: 204-210.
[141]Blesch A, Uy HS, Gril RJ, et al. Leukemia inhibitory factor augments neurotrophin expression and corticospinal axon growth after adult CNS injury. Neurosci, 1999, 19: 3556-3566.
[142]Lee IT, Green BA. Neuroprotective effects of basic fibroblast growth factor folowing spinal cord contusion injury in the rat. Neurotrauma, 1999, 16: 347-356.
[143]Muchmore SW, Sattler M, Liang H, et al. X-ray and NMR structure of human Bcl-XL, an inhibitor of programmedcell death. Nature. 1996, 381: 335-341.
[144]Nakamura K, Bossy-Wetzel E, Burns K, et al.Changes in endoplasmicreticulum luminal environment affect cell sensitivity to apoptosis. J Cell Biol, 2000, 150 :731-740.
[145]Wu S, Suzuki Y, Ejiri Y, Noda T, et al. Bone marrow stromal cellsenhance differentiation of cocultured neurosphere cells and promote regeneration of injured spinal cord.J. Neurosci. Res, 2003, 72: 343–351.
[146]Bradley JR. TNF-αmediated inflammatory disease. J Pathol, 2008, 214: 149-160.
[147]Lee YB, Yune TY, Baik SY,et al. Role of tumor necrosis factor-alpha in neuronal and glial apoptosis after spinal cord injury. Exp Neurol, 2000: 166:190-195.
[148]Conii AC, Raghupathi R, Trojanowski JQ, et al. Experimental brain injury induces regionally distinct apoptosis during the acute and delayed post-traumatic period. J Neurosei1, 1998, 18: 5663-5672.
[149]Harrington JF, Messier AA, Levine A, Szmydynger-Chodobska J, ChodobskiA: Shedding of tumor necrosis factor type 1 receptor after experimental spinalcord injury. J Neurotrauma, 2005, 22 :919-928.
[150]吴江,高建新,刘克敬,等.实验性大鼠脊髓损伤后运动能力及病理学变化的研究.山东大学学报(医学版), 2006, 144: 231-234.
[151]Marshall LF. Epidemiology and cost of central nervous systeminjury. Clin Neurosurg. 2000, 46: 105-112.
[152]Stevens RD, Bhardwaj A, Kirsh JR, et al. Critical care andperioperative in traumatic spinal cord injury. J Neurosurg Anesthesiol, 2003, 15: 215-229.
[153]沈文,王东.脊髓损伤实验性治疗进展.临床和实验医学杂志, 2008, 7: 551-553.
[154]卢旻鹏,权正学,刘渤.脊髓损伤动物模型的制备及评价.颈腰痛杂志, 2008, 29: 480-483.
[155]Hiruma S, Otsuka K, Satou T, et al. Simple and reproduciblemodel of rat spinal cord injury induced by a controlled corticalimpact device. Neurol Res, 1999, 21: 313-323.
[156]Yeo SJ, Hwang SN, Park SW, et al. Development of a rat modelof graded contusive spinal cord injury using a pneumatic impactdevice. J Korean Med Sci, 2004, 19: 574-580.
[157]Thomas AJ, Nockels RP, Pan HQ, et al. Progesterone isneuroprotective after acute experimental spinal cord traumainrats. Spine, 1999, 24: 2134-2138.
[158]Wyllie AH, Kerr JF, Currie AR. Cell death: the significance of apoptosis.Int Rev Cytol. 1980, 68: 251-306.
[159]Waring P, Kos FJ, Mullbacher A. Apoptosis or programmed cell death. Med Res Rev. 1991,11: 219-236.
[160]Yuan J. Molecular control of life and death. Curr Opin Cell Biol. 1995, 7: 211-214.
[161]Wada S,Yone K, Nagamine Y, et al. Apoptosis following spinal cord injury in rats and preventive effect of N-methyl D asparate receptor antagonist. J Neurosurg (Spina1), 1999, 91: 98.
[162]傅强,侯铁胜,鲁凯伍,等.大鼠脊髓急性损伤后神经细胞凋亡.中华创伤杂志, 2001, 17: 222-224.
[163]Tsujimoto Y. Cell death regulation by the Bcl-2 protein family in the mitochondria. J Cell Physiol, 2003, 195: 158-167.
[164]Yin XM, Oltvai ZN, Korsmeyer SJ. BH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerization with Bax. Nature 1994, 369 (6478): 321-323.
[165]Borner C. The Bcl-2 protein family: sensors and checkpoints for life-or-death decisions. Mol Immunol, 2003, 39: 615-647
[166]DeFalco M, Laforgia V, Fedele V, et al. Vasoactive intestinal peptide stimulation modulates the expression of Bcl-2 family members in the adrenal gland of the lizard Podarcis sicula. Histochem J, 2001, 33(11-12): 639-645
[167]Raisova M, Hossini AM, Eberle J, et al. The Bax/Bcl-2 ratio determines the susceptibility of human melanoma cells to CD95/Fas-mediated apoptosis. J Invest Dermatol 2001, 117: 333-340
[168]Shangary S, Johnson DE. Peptides derived from BH3 domains of Bcl-2 family members: a comparative analysis of inhibition of Bcl-2, Bcl-x (L) and Bax oligomerization, induction of cytochrome c release, and activation of cell death. Biochemistry 2002, 41(30): 9485-9495
[169]Moreau C, Cartron PF, Hunt A, et al. Minimal BH3 peptides promote cell death by antagonizing anti-apoptotic proteins. J Biol Chem 2003, 278: 19426-19435.
[170]赵伟峰,任先军,邓天琼,等.兔颈髓急性牵张性损伤后神经细胞凋亡相关蛋白表达的意义.中国矫形外科杂志, 2004, 12: 753-755.
[171]Chen DF, Schneider GE, Martinou JC, et a1. Bcl-2 promotes regenerationof severed axons in mammalian CNS. Nature, 1997, 385: 434.
[172]Fulle S, Mariggio M A, Belia S, et a1. Nerve growth factor inhibits apoptosis induced by S-100 binding in neuronal PC12 cells. Neurosie, 1997, 76: 159.
[173]Nakash1ma K, Yamashite K, Uesugi SJ, et a1. Temporal and spatial profile of apoptotie cell death in transient intracerebral mass lesion ofthe rat. J Neurotrauma, 1999, 16: 143-151.
[174]李振鹏,孔抗美,齐伟力.减压对慢性压迫性脊髓损伤大鼠凋亡基因bax和bcl-2表达的影响.现代医院, 2007, 7: 10-12
[175]Hoch RC, Rodriguez R, Manning T, et al. Effects of accidental trauma on cytokine and endotoxin prcduction. Crit Care Med, 1993, 197: 1566-l562.
[176]Kawakami M, Kaneko N, Anada H, et al. Measurment of interleukin-6, interlukin-10 and tumor necrmis factor-alpha levels in tissues and p1asma after thermal injury in mice. Surgery, 1997, 121: 440-448
[177]Loddiek SA, Turnbull AV, Rothwell NJ. Cerebral interleukin-6 is neuroprotective during permanent focal cerebral ischemia in the rat. J Cereb Blood Flow Metab, 1998, 18: 176-179.
[178]Nuttin B. Interleuklne-6 en besehadiging van het ruggemerg bij de rat Verh-K-Aead-Geneeskd-Beig,1995, 57: 315-349.
[179]Rot A. Endothetial cell binding of NAP-l/IL-8: role in neutrophile emigration. Immunology today, 1992, 13(2): 291-294.
[180]Kunihara T,Sasaki S,Shiiya N,et al. Lazaroid reduces production of IL-8 and IL-1 receptor antagonist in ischemic spinal cord injury. Ann Thorac Surg, 2000, 69: 792-798.
[181]刘清和,张兆辉,余绍祖.抗肿瘤坏死因子-α单克隆抗体对局灶脑缺血作用的初步研究J.中国神经精神疾病杂志,1999,25(3):169-170.
[182]郭平凡,陈福真.抗肿瘤坏死因子-α单克隆抗体减轻骨骼肌缺血再灌注损伤的研究J.中华实验外科杂志,2002,19(1): 72-73.
[183]刘亮,张万义,叶平.抗肿瘤坏死因子单克隆抗体对心肌细胞凋亡的影响.军医进修学院学报,2004,25(6):404-405
[2]Tyor WR, Avgeropoulos N, Ohlandt G, et al. Treatment of spinal cord impact injury in the rat with transforming growth factorbeta. J Neurol Sci, 2002, 200: 33-41.
[3]Beattie MS, Hermann GE, Rogers RC, et al. Cell death in models of spinal cord injury. Prog Brain Res, 2002, 137: 37-47.
[4]Blight AR, Leroy EC Jr, Heyes MP. Quinolinic acid accumulation in injured spinal cord: time course, distribution, and species differences between rat and guinea pig. J Neurotrauma. 1997; 14: 89-98.
[5]Schwartz M, Hauben ET. cell-based therapeutic vaccination for spinal cord injury. Prog.Brain Res, 2002, 137: 401-406.
[6]Young W. Spinal cord contusion models. Prog Brain Res, 2002, 137: 231-255.
[7]Lee M, Lee ES, Kim YS, et al. Ischemic injury-specific gene expression in the rat spinal cord injury model using hypoxia-inducible system. Spine, 2005, 30: 2729-2734.
[8]Balentine JD.Pathology of experimental spinal cord trauma:ultrastructure of axons and myelin. Lab Invest, 1978, 39: 254-266.
[9]Wagner F, Dhormann G, Bucy P. Histopathology of transitory traumatic paraplegia in the monkey. J Neurosurg, 1971, 35:272-276.
[10]Lee M, Lee ES, Kim YS, et al. Epidemiology, demographics, and pathophysiology of acute spinal cord injury. Spine, 2001, 26: S2-S12.
[11]Sekhon LH, Fehlings MG. Carlson GD, et al. Sustained spinal cord compression: part 1: time-dependent effect on long-tern pathophysiology. Bone Joint Surg Am, 2003, 85-A: 86-94.
[12]吴昊天,张英泽,李增炎,等.持续脊髓压迫与神经功能恢复的相关性研究.中国康复医学杂志, 2004, 19: 657-660.
[13]初同伟,吴梅英,马树支,等.不完全性急性脊髓损伤后脊髓病理改变、脊髓灰质血流量和运动诱发电位变化的实验研究.第三军医大学学报, 2000, 22: 750-753.
[14]Park E, Velumian AA, Fehlings G. The role of excitotoxicity in secondary mechanisms of spinal cord injury: a review with an emphasis on the implications for white matter degeneration. Neurotrauma, 2004, 21: 7540-7774.
[15]Akdemir H, Pasaoglu A. Histopathology of experimental spinal cord trauma. Comparison of treatment with TRH, naloxone, and dexamethasone.Res Exp Med (Berl), 1992, 192: 177-183.
[16]Tator CH, Koyanagi I. Vascular mechanisms in the pathophysiology of human spinal cord injury. J Neurosurg, 1997, 86: 483-492.
[17]Koyanagi I, Tator CH, Lea PJ. Three-dimensional analysis of the vascular system in the rat. Spinal cord with scanning electron microscopy of vascular corrosion casts. part2. acute spinal cord injury. Neurosurg, 1993, 33: 285-290.
[18]Koyanagi I, Tator CH, Theriault E. Silicone rubber microangiography of acute spinal cord injury in the rat. Neurosurg, 1993, 33: 285-290.
[19]Salzman SK, Acosta R, Beck G, et al. Spinal endothel contentis elevated moderate local trauma in the rat to levels associated with locomotor dysfunction after intrathecal injection. J Neurotrama, 1996, 13(2): 93-10.
[20]McKenzie-AL. Immunolocalization of endothelin in the traumatized spinal cord: relationship to blood-spinal cord barrier breakdown. J Neurotrauma, 1995, 12: 257.
[21]Yong W. Stratategies for the development of new and better pharma cological treatments for acute spinal cord injury. Adv Neurol, 1993, 59: 249
[22]Hall ED, Wolf DL, Braughler JM. Effects of a single large dose of methylprenisolone sodium succincton experimental post traumatic spinal cord schema: Dose response and time action analysis. J Neurosurg, 1984, 61: 124-130.
[23]Floyd RA, Waston JJ, Wong PK. Sensitive assay of hydroxy1free radical formation utilizing high pressure liquid chromatography with electrochemical detection of phenol and salicylate hydroxylation products. J Biochem Biophys Methods, 1984, 10: 221.
[24]Culmsee, C. Gerling, N. Landshamer, S. et al. Nitric oxide donors induce neurotrophin-like survival signaling and protect neurons against apoptosis. Mol. Pharmacol. 2005, 68: 1006-1017.
[25]Wu W. Neurol nitricoxide synthaseis induced in spinal neurons by traumatic injury. Neurosience, 1994, 61: 719
[26]Emery E, Aldana P, Bunge MB, et al. Apoptosis after traumatic human cord injury. Neurosurg, 2004, 89: 911-920.
[27]Matsushita Y, Shima K, Nawashiro H, et al. Real time monitoring of glutamate following fluid percussion brian injury with hypox in the rat. J Neurotrauma, 2000, 17: 143-153
[28]Krenz NR, Weaver LG.. Effect of spinal cord transtection on N Methyl aspartate receptors in the cord. J Neurotrauma, 1998, 15: 1027-1036
[29]Wrathall JR, Choiniere D, Teng YD. Dose deoendent reduction of tissue loss and functional impairment after spinal cord trauma with the AMPA/kainite antagonist NBQX. Neurosic, 1994, 14: 6598-6607
[30]Gaviria M, Privat A, Arbigny P, et al. Neuroprotective effects of gacyclidinea after experimental photochenmical spinal coed lesion in adult rats: dose window and time window effects. J Neurotrauma, 2000, 1719-173.
[31]Blomgren K, Mcrae A, Elmered A, et al.The calpainproteolytic system in neonatal hypoxic-isxhemia. Ann N Y Acad Sic, 1997, 825: 104-119
[32]Dinsmore JH, Solomon F. Inhibition of MAP-2ex-pression affects both morphological and cell divisionphenotypes of neuronal differentiation. Cell, 1991, 64(4): 817-826
[33]Chen J, Kanai Y, Cowan NJ, et al. Projection domainsof MAP-2and tau determine spacings between mir-crotubules in dendrites and axons. Nature, 1992, 360: 674-677
[34]Nunez J. Immature and mature variants of MAP-2 and tau propteins and neuronal plasticity. Trends Neurosci, 1988, 11: 477-479
[35]Yong J, Robak G, Liu D, et al. A sampling artifact inthe microdialysis study of changes in extracellular[Mg2+] upon apinal cord injury. Anal Biochem, 1997, 245: 203-206
[36]Balentine JD. Pathology of experimental spinal cordtrauma: The necrotic lesion as a function of vascularinjury. Lab Invest, 1978, 39: 236-253
[37]Das OK. Cellular biochemical and molecular aspectsof reperfusion on injury. Ann N Y Acad Sci, 1994, 723: 1-5
[38]Le YL, Shih K, Bao P, et al. Cytokine chemokine ex-pression in contusedrat spinal cord.NeurochemInt, 2000, 36: 417-425
[39]McTigue DM, Tani M, Krivacic K, et al. Selectivechemokine mRNA accumulation in the rat spinalcord after contusion injury. Neurosci Res, 1998, 53: 368-376
[40]Le YL, Shih K, Bao P, et al. Cytokine chemokine expression in contused rat spinal. Neurochem Int, 2000, 36: 417-425
[41]Growe MJ, Bresnahan JC, Shuman SL, et al. Apoptosis and delayed degeneration after spinal cord injuryin rats and monkey. Nature Medicine, 1997, 3: 73-76
[42]Guilin LI, Gregor BR, Mohammad FA, et al. Apoptosis and expression of bcl-2 after compression trau-ma to rat spinal cord. J Neuropha Exp Neurol, 1996, 55: 281-289
[43]Liu XZ, Xu XM, Hu R, et al. Neuronal and glial ap-optsis after traumatic spinal cord injury. J Neu-rosci, 1997, 17: 5394- 5406
[44]Yong C, Arnold PM, Zoubine MN, et al. Apoptosiscellular compartments of rats spinal cord after severecontusion injury.J Neuro trauma, 1998, 15: 459-472
[45]Hansen-Algenstaedt N, Algenstaedt P, Schaefer C, et al. Neural drivenangiogenesis by overexpression of nerve growth factor. Histochem Cell Biol, 2006, 12: 637-649.
[46]Yong W. Stratategies for the development of newand better pharma cological treatments for acutespinal cord injury. Adv Neurol, 1993, 59: 249
[47]Barres BA, Jacobson MD, Schmid R. Dose oligodendrocyte survive depend on axons? . Curr Biol, 1993, 3: 489-497
[48]Dusart I, Schwad EM. Secondary cell death and in-flammatory reaction after dorsal henisction of the ratspinal cord. Eur J Neurosci, 1994, 6: 712-724
[49]Shuman SL, Bresnahan JC, Beattie MS. Apoptosis ofmicroglia and oligodendrocytes after spinal crod con-tusion in rats. J Neurosci Res, 1997, 50: 798-808
[50]Casha Re, Yu W, Fehlings MG. Oligodendroglialapoptosiss occurs along degeneration anons and andis associated with FAS and P75 expression following spinal cord injury. Neuroscience, 2001, 103: 203-218
[51]Zain J, Huang YQ, Feng X, et al. Concentration-de-pendent dual effect of thombin on impaired growth/apoptosis or mitogenes in tumor cells. Blood, 2000, 95:3133-3189.
[52]Donovan FM, Pike CJ, Cotnan CW, et al. Thrombininduces apoptosis in cultured neurons and astrocytesvia a pathway requiring tyrosine kinase and RhoAactivities. J Neurosci, 1997, 17: 5316-5326.
[53]Greenamyre JT, Porter RH. Anatomy and physiology of glutamate in the CNS. . Neurology, 1994, 44(11 Suppl): S7-S1.
[54]Lu, C. L. Liang, H. J. Chen, S. D. et al. Injury severity and cell death mechanisms: effects of concomitant hypovolemic hypotension on spinal cord ischemiareperfusion in rats. Exp Neurol, 2004, 185: 120-132.
[55]Lu P, Jones LL, Tuszynski MH. BDNF-expressing marrow stromal cellssupport extensive axonal growth at sites of spinal cord injury. ExpNeurol, 2005, 191: 344-360.
[56]Koda M, HashimotoM, Murakami M, et al. Adenovirus vector-mediatedin vivo gene transfer of brain-derived neurotrophicfactor(BDNF) promotes rubrospinal axonal regeneration and functional recovery aftercomplete transaction of the adult rat spinal cord. J Neurotrauma, 2004, 21: 329-337.
[57]Jean I, Lavialle C, Barthelaix-Pouplard A, et al. Neurotrophin-3 specif-ically increases mature oligodendrocyte population and enhances remy-elination after chemical demyelination of adult rat CNS. Brain Res, 2003, 972: 110-118.
[58]HaggT, Baker KA, Emsley JG, et al. Prolonged local neurotrophin-3infusion reduces ipsilateral collateral sprouting of spared corticospinalaxons in adult rats. Neuroscience, 2005, 130: 875-887.
[59]Schreyer DJ, Skene JH. Injury-associated induction of GAP-43 expression displays axon branch specificity in rat dorsal root ganglion neurons. J Neurobiol, 1993, 24: 959-970.
[60]Kwon BK, Tetzlaff W. Spinal cord regeneration: from gene to transplants. Spine, 2001; 26(24 supp1): s13-s22.
[61]Herdegen T, Skene P, Bahr M. The c-Jun transcription factor--bipotential mediator of neuronal death, survival and regeneration. Trends Neurosci, l997; 20: 227-23l.
[62]Fernandes KH, Fan DP, Tsui BJ, et a1. Influence of the axotomy to cell body distance in rat rubrospinal and spinal motoneurons: differential regulation ofGAP-43, tubulins, and neurofilament-M. J Comp Neurol, l999; 4l4: 495-5l0.
[63]Frey K, Laux T, Xu L, et a1. Shared and unique roles of CAP23 and GAP43 in actin regulation, neurite outgrowth, and anatomical plasticity. J Cell Biol, 2000; 149: 1443- l454.
[64]Uchida K, Baba H, Maezawa Y, et a1. Progressive changes in neurofilament proteins and growth-associated protein-43 immunoreactivities at the site of cervical spinal cord compression in spinal hyperostotic mice. Spine, 2002, 27: 480- 486.
[65]Becker T, Bernhardt RR, Reinhard E, et al. Readiness of zebrafish brain neurons to regenerate a spinal axon correlates with differential expression of specific cell recognition molecules. J Neurosci, l998; l8: 5789-5803.
[66]Jung M, Petrausch B, Stuermer CA. Axon-regenerating retinal ganglion cells in adult rats synthesize the cell adhesion molecule L1 but not TAG-1 or SC-1. Mol Cell Neurosci, l997; 9: 116-l3l.
[67]Woolhead CL, Zhang Y, Lieberman AR, et a1. Differential effects of autologous peripheral nerve grafts to the corpus striatum of adult rats on the regeneration of axons of striatal and nigral neurons and on the expression of GAP-43 and the cell adhesion molecules N-CAM and L1. J Comp Neurol, l998, 39l: 259-273.
[68]Brosamle C, Huber AB, Fiedler M, et a1. Regeneration of lesioned corticospinal tract fibers in the adult rat induced by a recombinant, humanized IN-1 antibody fragment. J Neurosci, 2000, 20: 8061-8068.
[69]Fitch MT, Silver J. Activated macrophages and the blood-brain barrier: inflammation after CNS injury leads to increases in putative inhibitory molecules. Cell Tissue Ras. 1997, 290: 379-384.
[70]Faweett JW, Asher RA. The glial scar and central nervous system repair. Brain Ras Bull, l999, 49 :377-391
[71]Stichel CC, Hermanns S, Luhmann HJ. et al. Inhibition of collagen IV deposition promotes regeneration of injured CNS axons. Eur J Neurosci, l999, 11: 632-646.
[72]Barinaga M. New view of spinal cord injury. Science, 1996, 274: 1466
[73]崔志明,倪斌,蔡卫华,等.兔慢性颈脊髓压迫减压术后凋亡基因bo1-2和bax的表达.中国临床康复, 2004, 8: 7164-7165.
[74]傅强,侯铁胜,鲁凯伍,等.大鼠脊髓急性损伤后神经细胞凋亡及相关基因表达.中国脊柱脊髓杂志. 2001. 1l: 92-94.
[75]Polyak K, Xia Y, Zweier JL, et al. A model for p53-induced apoptosis. Nature. 1997, 389: 300-305.
[76]Ramer MS, Priestley JV, McMahon SB. Functional regeneration of sensory axons into the adult spinal cord. Nature, 2000, 403: 312-316.
[77]Philips MF, Mattiasson G, Wieloch T, et al. Neuroprotective and behavioral efficacy of nerve growth factor-transfected hippocampal progenitor cell transplants after experimental traumatic brain injury. J Neurosurg, 200l: 94: 765-774.
[78]McKerracher L, David S, Jackson DL, et al. Identification of myelin-associated glycoprotein as a major myelin-drived inhibitor of neurite growth.Neuron. l994, l3: 805-811.
[79]Mukhopadhyay G, Doherty P, Walsh FS, et a1. A novel role of myelin-associated glycoprotein as an inhibitor of axonal regeneration. Neuron, l994: l3: 757-767.
[80]Reynolds BA, Weiss S. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science, 1992, 255: 1707–1710.
[81]Caroni P, Schwab ME. Two membrane protein fractions from rat central myelin with inhibitory properties for neurite growth and fibroblast spreading. J Cell Biol. l988: l06: l28l-1288
[82]Fournier AE, GrandPre T, Strittmatter SM. Identification of a receptor mediating Nogo-66 inhibition of axona1 regeneration. Nature, 200l: 409: 34l-346.
[83]Liu BP, Fournier A, GrandPre T. et al. Myelin-associated glycoprotein as a functional ligand for the Nogo-66 receptor. Scieetce, 2002, 297: 1190-1193.
[84]Merkler D, Metz GA, Raineteau O, et a1.Locomotor reeovery in spinal cord injury rats treated with an antibody neutralizing the myelin-associated neurite growth inhibitor Nogo-A. J Neurosci, 200l, 21: 3665-3673.
[85]Li S, Strittmatter SM. Delayed systemic Nogo-66 receptor antagonist promotes recovery from spinal cord injury. J Neurosci, 2003, 23: 4219-4227.
[86]Tang X, Davies JE, Davies SJ. Changes in distilbution,cell associations, and protein expression 1evels of NG2, neurocan ,phosphacan,brevican, versican V2, and tenascin-C during acute to chronic maturation of spinal cord scar tissue. JNeurosci Res, 2003, 71: 427-444
[87]Davies SJ, Goucher DR, Doller C, et a1. Robust regeneration of aduh sensory axons in degenerating white matter of the adult rat spinal cord.J Neurosci, l999, l9: 58l0-5822.
[88]Bradburv EJ, Moon LD, Popat RJ, el al. Chondroitinase ABC promotes functional recovery after spinal cord injury. Nature, 2002: 416: 636-640
[89]Moon LD, Asher RA, Fawcett JW, et al. Limited growth of severed CNS axons after treatment of adult rat brain with hyaluronidase. J Neurosci Res, 2003, 7l: 23-37.
[90]Azanchi R, Eternal G, Gupta R, et a1.Combined demyelination plus Schwann cell transplan tation therapy increases spread of cells and axonal regeneration following contusion injury. Neurotrauma, 2004, 21: 775-788.
[91]Joosten EA, Houweling DA. Local acute application of BDNF in the lesioned spinal cord and inflammatory and an tioxidant effects. Neu- roreport, 20o4, 15: 1163-1166.
[92]Takami T. Schwann cell but not olfactory ensheathing glia transplants improve hindlimb locomotor performance in the moderately contused adult rat thoracic spinal cord. J. Neurosci, 2002, 22: 6670–6681.
[93]Chen A, Xu XM, Kleitman N, et al. Methylprednisolone administration improves axonal regeneration into Schwann cell grafts in transected adult rat thoracic spinal cord. Exp. Neurol, 1996, 138: 261–276.
[94]Xu XM, Guenard V, KleitmanN, et a1. A combination of BDNF and NT-3 promotes supraspinal axonal regeneration into Schwann cell grafts in adult rat thoracic spinal cord. Exp Neurol, 1995, 134: 261 - 272
[95]Barakat DJ, Gaglani SM, Neravetla SR, et a1. Survival,integration, and axon growth suppo rt of gila transplanted into the chronically con·tused spinal cord.Cell Transplant, 2005, 14: 225-240.
[96]HIll CE, Moon LD, Weed PM, et a1. Labeled Schwann cell tcal-plantation: cell loss, host Schwann cell replacement, and strategies to enhance surviva1. Glia, 2006, 53: 338-343
[97]Ramon-Cueto A, Plant G.W, Avila J,et al. Long-distance axonal regeneration in the transected adult rat spinal cord is promoted by olfactory ensheathing glia transplants. J Neurosci, 1998, 18: 3803-3815.
[98]Guest JD. The ability of cultured human Schwann cells within PAN/PVC guidance channels to support regeneration in the transected nude rat spinal cord. Can. J Neurol Sci, 1996, 23: S1–S2.
[99]Li Y, Field P M, Raisman G.. Repair of adult rat corticospinal tract by transplants of olfactory ensheathing cells. Science, 1997, 277: 2000–2002.
[100]Bianco JI., Perry C, Harkin DG., et al. Neurotrophin 3 promotes purification and proliferation of olfactory ensheathing cells from human nose. Glia, 2004, 45: 111–123.
[101]Kato T, Honmou O, Uede T, et al. Transplantation of human olfactory ensheathing cells elicits remyelination of demyelinated rat spinal cord. Glia, 2000, 30: 209–218.
[102]Barnett SC. Identification of a human olfactory ensheathing cell that can effect transplant-mediated remyelination of demyelinated CNS axons. Brain, 2000, 123: 1581–1588.
[103]Guest J, Herrera LP, Qian T. Rapid recovery of segmental neurological function in a tetraplegic patient following transplantation of fetal olfactory bulb-derived cells. Spinal Cord, 2006, 44: 135–142.
[104]Huang, H. Influence of patients’age on functional recovery after transplantation of olfactory ensheathing cells into injured spinal cord injury. Chin Med J (Engl.), 2003, 116: 1488–1491.
[105]Dobkin BH, Curt A, Guest J. Cellular transplants in China: observational study from the largest human experiment in chronic spinal cord injury. Neurorehabil. Neural Repair, 2006, 20: 5–13.
[106]Jang JE, Shaw K, Yu XJ,et a1.Specific and stable gene transfer to human embryonic stem cells using pseudotyped lentiviral veclors.Stem Cells Dev, 2006, 15: 109-117.
[107]McDonald JW. Transplanted embryonic stem cells survive, differentiate and promote recovery in injured spinal cord. Nature Med., 1999, 5: 1410–1412.
[108]Harper JM. Axonal growth of embryonic stem cell-derived motoneurons in vitro and in motoneuron-injured adult rats. PNAS, 2004, 101: 7123–7128.
[109]Gage FH. Mammalian neural stem cells. Science, 2000, 287: 1433- 1441.
[110]王岩峰,吕刚,李花,等.神经干细胞移植对大鼠脊髓损伤后BDNF- GAP-43 (GAP-43)基因表达的影响.中华矫形外科杂志, 2004, 12: 1870-1872.
[111]Tnda H, Takahushi J, Mizoguchi A, et a1. Neurons generated from adalt rat hippocampal stem cells from functional glutama-rgic and GABAergic synapses in vitro. Exp Nerol, 2000, 165: 66-76
[112]Nakamura M, Toyama Y, Okano H. Transplantation of neural stem cells for spinal cord injury. Rinsho Shinkeigaku, 2005, 45: 874 - 876
[113]James AT, Joseph IE, Sander SS, et al. Embryonic Stem Cell Lines Derived from Human Blastocysts. Science, 1998, 282: 1145-1147.
[114]Fred HG, Inder MV. Stem cells at the dawn of the 21st century. PNAS, 2003, 100: 11817-11818.
[115]Kawaguchi S, lseda T, Nishio T. Effects of an embryonic repair graft on recovery from spinal cord injury. Prog Brain Res, 2004, 144: 155– 162.
[116]Peterson CA, Murphy RJ, Dupont-Versteegden EE, et a1. Cycling exercise and fetal spinal cord transplantation act synergistically on atro- phied muscle following chronic spinal cord injury in rats. Neurorehabil Neural Repair, 2000, 14: 85-91
[117]Cao Q, Benton RL, Whittemore SR. Stem cell repair of central nervous system injury. J. Neurosci Res, 2002, 68: 501–510.
[118]Daniel RM, Richard LG, David G. Stem Cell Biology. Copyright by Cold Spring Harbor Laboratory Press, Cold Spring Laboratory, New York. 2001: 10.
[119]Herrera J. Embryonic-derived glial-restricted precursor cells (GRP cells) can differentiate into astrocytes and oligodendrocytes in vivo. Exp. Neurol, 2001, 171: 11–21.
[120]Hill CE. Acute transplantation of glial-restricted precursor cells into spinal cord contusion injuries: survival, differentiation, and effects on lesion environment and axonal regeneration. Exp. Neurol., 2004, 190: 289–310.
[121]Gerald D. F, Ruth LF. Stem cells: science, policy, and ethics. J Clinical Investi, 2004, 114: 1364-1370.
[122]Schultz SS. Adult stem cell application in spinal cord injury. Curr Drug Targets, 2005, 6: 63–73.
[123]Koshizuka S, Okada S, Okawa A, et al. Transplanted hematopoietic stem cells from bone marrow differentiate into neural lineage cells and promote functional recovery after spinal cord injury in mice. J. Neuropathol. Exp. Neurol, 2004, 63: 64–72.
[124]Koda M, Okada S, Nakayama T, et al. Hematopoietic stem cell and marrow stromal cell for spinal cord injury in mice. Neuroreport, 2005, 16: 1763–1767.
[125]Ankeny DP, Mctigue DM, Jakeman LB, et a1. Bone marrow transplants provide tissue protection and directional guidance for axons after contusive spinal cord iury in rats. Exp Neurol, 2004, 190: 17– 31.
[126]Li Y, Chen J, WangL, et a1.Treatment of stroke in rat with intracarotid administration of marrow stromal cells. Neurology, 2001, 56: 1666-1672.
[127]Mahmood A, Lu D, Wang L, et a1. Intracerebral transplantation of n-ITOw stromal cells cultured with neurotrophic factors promotes functional recovery in adult rats subjected to traumatic brain injury. Neurotrauma, 2002, 19: 1609-1617.
[128]Chen X, Katakowski M, Li Y, et a1. Human bone nlarrow stromal cell cultures conditioned by traumatic brain tissue extracts:growth factor production. Neurosci Res, 2002, 69: 687-691
[129]Satake K, Lou J, Lenke LG. Migration of mesenchymal stem cells through cerebrospinal fluid into injury spinal cord tissue. Spine, 2004, 29(18): 1971-1979.
[130]lnoue M, Honmou O, Oka S, et a1. Comparative analysis of cemyelinating potential of focal an d intravenous administration of autologons bone nlarrow cells into the rat demyelinated spinal cord. Gila, 2003, 44: 111-118.
[131]Byung H, Yoon H, Cheol-Hee A, et al. A hypoxia-inducible gene expression system using erythropoietin 3 untranslated region for the gene therapy of rat spinal cord injury. Neuroscience Letters, 2007, 412: 118-122.
[132]Piantino J, Burdick JA, Goldberg D, et al. An injectable,biodegradable hydrogel for trophic factor delivery enhances axonal rewiring and improves performance after spinal cord injury. Exp Neurol, 2006, 23: 245-251.
[133]Shumsky JS, Tobias CA, Tumolo M, et al. Delayed transplantation of fibroblasts genetically modified to secrete BDNF and NT-3 into a spinal cord injury site is associated with limited recovery of function. Exp Neurol, 2003, 184: 114-130.
[134]McTigue DM, Horner PJ, Strokes BT, et al. Neurotrophin-3 and neurotrophic factors induce oligodendrocyte prolifiration and myelination ofregenerating axons in the contused adult rat spinal cord. Neurosci, 1998, 18: 5354-5365.
[135]Spenger C, Hyman C, Studer L, et al. Efects of BDNF on dopaminergic, serotonergic, and GABA ergic neurons in cultures of human fetal ventral mesencephalon. . Exp Neurol, 1995, 133: 50-63
[136]Jakeman LB, Wei P, Guan Z, et al. Related articles brain-derived neurotrophic factor stimulates hindlimb stepping and sprouting of cholinergic fibers after spinal cord injury. . Exp Neurol, 1998, 154: 170-184.
[137]Hains BC, Fullwood SD, Eaton J. Subdural engraftment of serotonergic neurons folowing spinal hemisection restores spinal serotonin, downregulates serotonin transporter, and increases BDNF tissue content in rat. Brain .Research, 2001, 913: 35-46.
[138]Vavrek R, Girgis J, Tetzlaff W, et al. BDNF promotes connections of corticospinal neurons onto spared descending interneurons in spinal cord injured rats. Brain, 2006, 129(Pt. 6): 1534-1545.
[139]Taylor SJ, Rosenzweig ES, McDonald JW, et al. Delivery of neurotrophin-3 from fibrin enhances neuronal fiber sprouting after spinal cord injury, Control. Release, 2006, 113226-235.
[140]Effect of controlled delivery of neurotrophin-3 from fibrin on spinal cord injury in a long term model Sara. Taylor a, Shelly E. J Control Release, 2006, 116: 204-210.
[141]Blesch A, Uy HS, Gril RJ, et al. Leukemia inhibitory factor augments neurotrophin expression and corticospinal axon growth after adult CNS injury. Neurosci, 1999, 19: 3556-3566.
[142]Lee IT, Green BA. Neuroprotective effects of basic fibroblast growth factor folowing spinal cord contusion injury in the rat. Neurotrauma, 1999, 16: 347-356.
[143]Muchmore SW, Sattler M, Liang H, et al. X-ray and NMR structure of human Bcl-XL, an inhibitor of programmedcell death. Nature. 1996, 381: 335-341.
[144]Nakamura K, Bossy-Wetzel E, Burns K, et al.Changes in endoplasmicreticulum luminal environment affect cell sensitivity to apoptosis. J Cell Biol, 2000, 150 :731-740.
[145]Wu S, Suzuki Y, Ejiri Y, Noda T, et al. Bone marrow stromal cellsenhance differentiation of cocultured neurosphere cells and promote regeneration of injured spinal cord.J. Neurosci. Res, 2003, 72: 343–351.
[146]Bradley JR. TNF-αmediated inflammatory disease. J Pathol, 2008, 214: 149-160.
[147]Lee YB, Yune TY, Baik SY,et al. Role of tumor necrosis factor-alpha in neuronal and glial apoptosis after spinal cord injury. Exp Neurol, 2000: 166:190-195.
[148]Conii AC, Raghupathi R, Trojanowski JQ, et al. Experimental brain injury induces regionally distinct apoptosis during the acute and delayed post-traumatic period. J Neurosei1, 1998, 18: 5663-5672.
[149]Harrington JF, Messier AA, Levine A, Szmydynger-Chodobska J, ChodobskiA: Shedding of tumor necrosis factor type 1 receptor after experimental spinalcord injury. J Neurotrauma, 2005, 22 :919-928.
[150]吴江,高建新,刘克敬,等.实验性大鼠脊髓损伤后运动能力及病理学变化的研究.山东大学学报(医学版), 2006, 144: 231-234.
[151]Marshall LF. Epidemiology and cost of central nervous systeminjury. Clin Neurosurg. 2000, 46: 105-112.
[152]Stevens RD, Bhardwaj A, Kirsh JR, et al. Critical care andperioperative in traumatic spinal cord injury. J Neurosurg Anesthesiol, 2003, 15: 215-229.
[153]沈文,王东.脊髓损伤实验性治疗进展.临床和实验医学杂志, 2008, 7: 551-553.
[154]卢旻鹏,权正学,刘渤.脊髓损伤动物模型的制备及评价.颈腰痛杂志, 2008, 29: 480-483.
[155]Hiruma S, Otsuka K, Satou T, et al. Simple and reproduciblemodel of rat spinal cord injury induced by a controlled corticalimpact device. Neurol Res, 1999, 21: 313-323.
[156]Yeo SJ, Hwang SN, Park SW, et al. Development of a rat modelof graded contusive spinal cord injury using a pneumatic impactdevice. J Korean Med Sci, 2004, 19: 574-580.
[157]Thomas AJ, Nockels RP, Pan HQ, et al. Progesterone isneuroprotective after acute experimental spinal cord traumainrats. Spine, 1999, 24: 2134-2138.
[158]Wyllie AH, Kerr JF, Currie AR. Cell death: the significance of apoptosis.Int Rev Cytol. 1980, 68: 251-306.
[159]Waring P, Kos FJ, Mullbacher A. Apoptosis or programmed cell death. Med Res Rev. 1991,11: 219-236.
[160]Yuan J. Molecular control of life and death. Curr Opin Cell Biol. 1995, 7: 211-214.
[161]Wada S,Yone K, Nagamine Y, et al. Apoptosis following spinal cord injury in rats and preventive effect of N-methyl D asparate receptor antagonist. J Neurosurg (Spina1), 1999, 91: 98.
[162]傅强,侯铁胜,鲁凯伍,等.大鼠脊髓急性损伤后神经细胞凋亡.中华创伤杂志, 2001, 17: 222-224.
[163]Tsujimoto Y. Cell death regulation by the Bcl-2 protein family in the mitochondria. J Cell Physiol, 2003, 195: 158-167.
[164]Yin XM, Oltvai ZN, Korsmeyer SJ. BH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerization with Bax. Nature 1994, 369 (6478): 321-323.
[165]Borner C. The Bcl-2 protein family: sensors and checkpoints for life-or-death decisions. Mol Immunol, 2003, 39: 615-647
[166]DeFalco M, Laforgia V, Fedele V, et al. Vasoactive intestinal peptide stimulation modulates the expression of Bcl-2 family members in the adrenal gland of the lizard Podarcis sicula. Histochem J, 2001, 33(11-12): 639-645
[167]Raisova M, Hossini AM, Eberle J, et al. The Bax/Bcl-2 ratio determines the susceptibility of human melanoma cells to CD95/Fas-mediated apoptosis. J Invest Dermatol 2001, 117: 333-340
[168]Shangary S, Johnson DE. Peptides derived from BH3 domains of Bcl-2 family members: a comparative analysis of inhibition of Bcl-2, Bcl-x (L) and Bax oligomerization, induction of cytochrome c release, and activation of cell death. Biochemistry 2002, 41(30): 9485-9495
[169]Moreau C, Cartron PF, Hunt A, et al. Minimal BH3 peptides promote cell death by antagonizing anti-apoptotic proteins. J Biol Chem 2003, 278: 19426-19435.
[170]赵伟峰,任先军,邓天琼,等.兔颈髓急性牵张性损伤后神经细胞凋亡相关蛋白表达的意义.中国矫形外科杂志, 2004, 12: 753-755.
[171]Chen DF, Schneider GE, Martinou JC, et a1. Bcl-2 promotes regenerationof severed axons in mammalian CNS. Nature, 1997, 385: 434.
[172]Fulle S, Mariggio M A, Belia S, et a1. Nerve growth factor inhibits apoptosis induced by S-100 binding in neuronal PC12 cells. Neurosie, 1997, 76: 159.
[173]Nakash1ma K, Yamashite K, Uesugi SJ, et a1. Temporal and spatial profile of apoptotie cell death in transient intracerebral mass lesion ofthe rat. J Neurotrauma, 1999, 16: 143-151.
[174]李振鹏,孔抗美,齐伟力.减压对慢性压迫性脊髓损伤大鼠凋亡基因bax和bcl-2表达的影响.现代医院, 2007, 7: 10-12
[175]Hoch RC, Rodriguez R, Manning T, et al. Effects of accidental trauma on cytokine and endotoxin prcduction. Crit Care Med, 1993, 197: 1566-l562.
[176]Kawakami M, Kaneko N, Anada H, et al. Measurment of interleukin-6, interlukin-10 and tumor necrmis factor-alpha levels in tissues and p1asma after thermal injury in mice. Surgery, 1997, 121: 440-448
[177]Loddiek SA, Turnbull AV, Rothwell NJ. Cerebral interleukin-6 is neuroprotective during permanent focal cerebral ischemia in the rat. J Cereb Blood Flow Metab, 1998, 18: 176-179.
[178]Nuttin B. Interleuklne-6 en besehadiging van het ruggemerg bij de rat Verh-K-Aead-Geneeskd-Beig,1995, 57: 315-349.
[179]Rot A. Endothetial cell binding of NAP-l/IL-8: role in neutrophile emigration. Immunology today, 1992, 13(2): 291-294.
[180]Kunihara T,Sasaki S,Shiiya N,et al. Lazaroid reduces production of IL-8 and IL-1 receptor antagonist in ischemic spinal cord injury. Ann Thorac Surg, 2000, 69: 792-798.
[181]刘清和,张兆辉,余绍祖.抗肿瘤坏死因子-α单克隆抗体对局灶脑缺血作用的初步研究J.中国神经精神疾病杂志,1999,25(3):169-170.
[182]郭平凡,陈福真.抗肿瘤坏死因子-α单克隆抗体减轻骨骼肌缺血再灌注损伤的研究J.中华实验外科杂志,2002,19(1): 72-73.
[183]刘亮,张万义,叶平.抗肿瘤坏死因子单克隆抗体对心肌细胞凋亡的影响.军医进修学院学报,2004,25(6):404-405
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