再次修复远侧吻合口促进神经移植后轴突再生的研究
|
摘要
周围神经缺损的修复是外科领域至今尚未解决的难题之一。尽管许多学者对异体神经移植、异种神经移植、非神经组织材料替代移植、组织工程人工神经移植修复神经缺损进行了大量的研究,但自体神经移植仍是目前临床用于修复神经缺损的首选方法。然而,自体神经移植特别是长段神经移植后,临床疗效仍不尽人意。长段移植神经的血供、移植神经周围的瘢痕组织、跨越两个吻合口对神经再生的影响等因素,是目前许多学者重点关注的问题。但是,关于远侧吻合口与近侧吻合口在影响神经再生方面的作用有何不同?依据神经再生的速度,择期切除远侧吻合口并进行重新吻合后,对促进再生轴突跨越远端吻合口的作用如何?择期切除远侧吻合口,对相关感觉、运动神经元功能状况的影响如何?国内外相关研究少见。
作为阐明上述问题系列研究的一部分,本课题采用大鼠坐骨神经原位移植模型,应用免疫组化、RT-PCR、Western-blot等技术,观察神经吻合口内I型和III型胶原的表达变化;观察择期切除远侧吻合口再修复后,相关感觉、运动神经元内AChE、ACP、BDNF的表达变化。以明确远侧吻合口瘢痕增生的情况;明确择期切除再吻合后瘢痕组织与神经轴突再生的状况;明确择期切除远侧吻合口,对相关感觉、运动神经元部分功能状况的影响。
研究结果:1、择期切除移植神经的远侧吻合口再吻合后,术后4w时,实验组与对照组I型和III型胶原的表达无显著性差异,8w时实验组明显低于对照组。2、择期切除移植神经的远侧吻合口再吻合后,实验组运动神经元内AChE、ACP损伤性反应依然存在,但与对照组相比损伤反应减轻,差异具有显著性。3、择期切除移植神经的远侧吻合口再吻合后,BDNF在相应脊髓和背根神经节中再次出现表达高峰,与对照组有显著性差异。
研究结论:1、择期切除移植神经的远侧吻合口再吻合后,明显减轻了远侧吻合口瘢痕组织的增生,有利于再生轴突跨越远端吻合口。2、择期切除移植神经的远侧吻合口再吻合后,尽管相应运动神经元仍存在酶学指标的损伤性反应,但其损伤程度明显减轻。3、择期切除移植神经的远侧吻合口再吻合后,相关感觉、运动神经元内促进轴突再生的能力再次得到激活和增强。
It is one of the difficult problems left unsolved in surgical field to repair the peripheral nerve defect.Although many scholars have investigated a lot on xenogenous nerve graft, heterogenous nerve graft, alternating autologous biological tissue and tissue-engineered bioartificial nerve to repair nerve defect, autologous nerve graft has always been the first consideration for nerve restorative procedure in clinic. However, the healing efficacy of autologous nerve graft is still not so satisfactory, especially long nerve graft. Blood supply of long nerve graft, surrounding scar tissue and axons stepping over two anastomotic stomata influence the nerve regeneration are concentrated on by many scholars. But if there were the differences between the impacts from distal and proximal anastomotic stoma on nerve regeneration, how are the effects on regenerated axon growing through distal anastomotic stoma of re-anastomosis after selective excision of distal anastomotic stoma according to the speed of nerve regeneration? How will affect the function of sensory and motor neurons after selective excision of distal anastomotic stoma? These are still rare all over the world on these studies.
Purposes:
The distal anastomotic stoma after nerve graft was excised and re- anastomsed, then we observed whether hyperplasia of scar tissue could be suppressed and the growth through distal anastomotic stoma of regenerated axon could be promoted. Meanwhile, functional status of axons was observed which had grown to distal anastomotic stoma to see whether axonal growth promotion could be aroused again by sensory and motor neurons.
Methods:
Sciatic nerve graft in situ was built on Wistar mouse. The mice were grouped randomly into sham operation group (nerve exposed only), control group (nerve graft in situ) and experimental group (excision and repair distal anastomotic stoma 8 weeks after nerve graft). Nerve tissue of distal anastomotic stoma, corresponding spinal cord and dorsal root ganglion were excised in different time spots. Immunohistochemical methods were used to test the expression changes of collagen type I and III ,which could obtain the condition of hyperplastic scar tissue in distal anastomotic stoma. The changes of AChE, ACP and BDNF in sensory and motor neurons after re-anatomsis were detected by immunohistochemical methods, Rt-PCR and western blot .These changes could identify the state of axon regeneration and scar tissue and the influences on partical function of corresponding sensory and motor neurons.
Results:
1. There was no significant variation in expression of collagen type I and III in control group and experimental group 4 weeks after the re-anastomosis and 8 weeks later. It was lower in experimental group compared with control group.
2. AChE and ACP leading to impaired reaction of motor neuron still existed after re-anastomosis in experimental group. There was significant deviation of AChE expression in experimental group than that of control group from 7th to 28th day (P<0.01).There was significant deviation of ACP expression in experimental group lower than control group from 7th to 56th day (P<0.01)
3. After the re-anastomosis, there was a BDNF expression peak in spinal cord and dorsal root ganglion in 14th day and the deviation was significant between control group and experimental group(P<0.01).The expression went down gradually after 42th day .At 56th day, BDNF expression is still higher than that of control group (P<0.01).
Conclusions:
1. Re-anastomosis after selective excision of distal anastomotic stoma strongly suppresses hyperplasia of scar tissue and is helpful to stimulate axon growing throu- gh distal anas- tomotic stoma.
2. Although there is still enzyme changes caused by selective excision in motor neurons,but the injury degree is obviously less than that caused by previous injury.
3. Capability of promoting axon regeneration is aroused and enhanced in sensory and motor neurons after the re-anastomosis.
4. According to the speed of peripheral nerve regeneration, re-anastomosis after selective excision of distal anastomotic stoma could suppress hyperplasia of scar tissue and promote regenerative axon growing through distal anastomotic stoma preferably. It could stimulate efficiently the grown axons which have reached distal anastomotic stoma, which could evoke functional status of promoting axon growth in the correlated sensory and motor neurons once more.
作为阐明上述问题系列研究的一部分,本课题采用大鼠坐骨神经原位移植模型,应用免疫组化、RT-PCR、Western-blot等技术,观察神经吻合口内I型和III型胶原的表达变化;观察择期切除远侧吻合口再修复后,相关感觉、运动神经元内AChE、ACP、BDNF的表达变化。以明确远侧吻合口瘢痕增生的情况;明确择期切除再吻合后瘢痕组织与神经轴突再生的状况;明确择期切除远侧吻合口,对相关感觉、运动神经元部分功能状况的影响。
研究结果:1、择期切除移植神经的远侧吻合口再吻合后,术后4w时,实验组与对照组I型和III型胶原的表达无显著性差异,8w时实验组明显低于对照组。2、择期切除移植神经的远侧吻合口再吻合后,实验组运动神经元内AChE、ACP损伤性反应依然存在,但与对照组相比损伤反应减轻,差异具有显著性。3、择期切除移植神经的远侧吻合口再吻合后,BDNF在相应脊髓和背根神经节中再次出现表达高峰,与对照组有显著性差异。
研究结论:1、择期切除移植神经的远侧吻合口再吻合后,明显减轻了远侧吻合口瘢痕组织的增生,有利于再生轴突跨越远端吻合口。2、择期切除移植神经的远侧吻合口再吻合后,尽管相应运动神经元仍存在酶学指标的损伤性反应,但其损伤程度明显减轻。3、择期切除移植神经的远侧吻合口再吻合后,相关感觉、运动神经元内促进轴突再生的能力再次得到激活和增强。
It is one of the difficult problems left unsolved in surgical field to repair the peripheral nerve defect.Although many scholars have investigated a lot on xenogenous nerve graft, heterogenous nerve graft, alternating autologous biological tissue and tissue-engineered bioartificial nerve to repair nerve defect, autologous nerve graft has always been the first consideration for nerve restorative procedure in clinic. However, the healing efficacy of autologous nerve graft is still not so satisfactory, especially long nerve graft. Blood supply of long nerve graft, surrounding scar tissue and axons stepping over two anastomotic stomata influence the nerve regeneration are concentrated on by many scholars. But if there were the differences between the impacts from distal and proximal anastomotic stoma on nerve regeneration, how are the effects on regenerated axon growing through distal anastomotic stoma of re-anastomosis after selective excision of distal anastomotic stoma according to the speed of nerve regeneration? How will affect the function of sensory and motor neurons after selective excision of distal anastomotic stoma? These are still rare all over the world on these studies.
Purposes:
The distal anastomotic stoma after nerve graft was excised and re- anastomsed, then we observed whether hyperplasia of scar tissue could be suppressed and the growth through distal anastomotic stoma of regenerated axon could be promoted. Meanwhile, functional status of axons was observed which had grown to distal anastomotic stoma to see whether axonal growth promotion could be aroused again by sensory and motor neurons.
Methods:
Sciatic nerve graft in situ was built on Wistar mouse. The mice were grouped randomly into sham operation group (nerve exposed only), control group (nerve graft in situ) and experimental group (excision and repair distal anastomotic stoma 8 weeks after nerve graft). Nerve tissue of distal anastomotic stoma, corresponding spinal cord and dorsal root ganglion were excised in different time spots. Immunohistochemical methods were used to test the expression changes of collagen type I and III ,which could obtain the condition of hyperplastic scar tissue in distal anastomotic stoma. The changes of AChE, ACP and BDNF in sensory and motor neurons after re-anatomsis were detected by immunohistochemical methods, Rt-PCR and western blot .These changes could identify the state of axon regeneration and scar tissue and the influences on partical function of corresponding sensory and motor neurons.
Results:
1. There was no significant variation in expression of collagen type I and III in control group and experimental group 4 weeks after the re-anastomosis and 8 weeks later. It was lower in experimental group compared with control group.
2. AChE and ACP leading to impaired reaction of motor neuron still existed after re-anastomosis in experimental group. There was significant deviation of AChE expression in experimental group than that of control group from 7th to 28th day (P<0.01).There was significant deviation of ACP expression in experimental group lower than control group from 7th to 56th day (P<0.01)
3. After the re-anastomosis, there was a BDNF expression peak in spinal cord and dorsal root ganglion in 14th day and the deviation was significant between control group and experimental group(P<0.01).The expression went down gradually after 42th day .At 56th day, BDNF expression is still higher than that of control group (P<0.01).
Conclusions:
1. Re-anastomosis after selective excision of distal anastomotic stoma strongly suppresses hyperplasia of scar tissue and is helpful to stimulate axon growing throu- gh distal anas- tomotic stoma.
2. Although there is still enzyme changes caused by selective excision in motor neurons,but the injury degree is obviously less than that caused by previous injury.
3. Capability of promoting axon regeneration is aroused and enhanced in sensory and motor neurons after the re-anastomosis.
4. According to the speed of peripheral nerve regeneration, re-anastomosis after selective excision of distal anastomotic stoma could suppress hyperplasia of scar tissue and promote regenerative axon growing through distal anastomotic stoma preferably. It could stimulate efficiently the grown axons which have reached distal anastomotic stoma, which could evoke functional status of promoting axon growth in the correlated sensory and motor neurons once more.
引文
[1] Schmitt A B,Breuer S,Liman J,et a1.Identification of regeneration-associated genes after central and peripheral nerve injury in the adult rat[J].BMC Neuroscience,2003,4: 1471-2202,
[2] Keith F,Tessa G.Axonal regeneration in the peripheral and central nervous systems- current issues and advances [J].J Neurol Sci,2004,31:142-156
[3] Torigoe K, Hashimoto K, Lundborg G. A role of migratory Schwann cells in a conditioning effect of peripheral nerve regeneration [J]. Exp Neurol,1999,160(1):99-108.
[4] Somkova I,Krieglstein J.Neuroprotection mediated via neurotrophic factors and induction of neurotrophic factors[J]. Brain Res Rev,1999,30(2):176-188.
[5] Frostick SP,Yin Q,Kemp GJ.Schwann cells,neurotrophic factors and peripheral nerve regeneration [J].Microsurgery,1998,l8(7):397-405.
[6] Neuberger TJ,CeVries GH.Distribution of fibroblast growth factor in cultured dorsal root ganglion neurons and Schwann cells localization during maturation in vitro[J].J Neurocytol,1993,22(6):436-448.
[7] Dubovy P.Schwann cells and endconeurial extracellular matrix molecules as potential cues for sorting of regenerated axons[J].Anat Soi Int,2004,79(4):198-208
[8] Li X,Lynn BD,Olson C,et al.Connexin29 expression,immunocytochemistry and freeze- fracture replica immunogold labeling (FRIL)in sciatic nerve.Eur J Neurosci.2002, 16:795-806
[9] Dezawa M,Mutoh T,Dezawa A,et al.Putative gap junctional communication between axon and regenerating Schwann cells during mammalian peripheral nerve regeneration. Neuroscience,1998,85:663-667.
[10] Sieard RE.Differential inflammatory and immunological responses in tissue regeneration and repair [M].Ann N Y Acad Sci,2002,961:368-371
[11] Mantovani A,Sozzani S,Locati M,et a1.Macrophage polarization:Tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes[J].Trends Immune, 2002,23(11): 549-560
[12]李立钧,陈统一.周围神经损伤与再生中的细胞和细胞分子.国外医学:骨科学分册,2004,25(5):280-283.
[13] Akassoglou K,Yu WM,Akpinar P,et a1.Fibrin inhibits peripheral nerve remyelination by regulating Schwann cell differentiation [J].Neuron,2002,33(6):861-875
[14] Mligiliche N,Endo K,Okamoto K,et al. Extracellular matrix of human amion manufactured into tubes as conduits for peripheral nerve regeneration[J].J BiomedMater Res 2002; 63 (5): 591-600.
[15] Takeda Y ,Murakami Y ,Asou H,et a1.The roles of cell adhesion molecules on the formation of peripheral myelin.Keio J Med,2001.50:240-248
[16] Fox GB,Kjoller C,Murphy K J,et al.The modulations of NCAM polysialylation state that follow transient global ischemia are brief on neurons but enduring on glia. J Neuropathol Exp Neurol,2001,60(2):132-140
[17] Paddok HN, Schultz GS, Barker HV,et al.Analysis of gene expression patterns in human postburn hypertrophic scars .J Bum Care Rehbil 2003;24(6):371-377
[18]陈中伟主编.周围神经损伤基础与临床研究.人民卫生出版社,1996:120-135
[19] Stamenkovic I,Extracellular matric remodeling :the role of matric metalloprtenases Pathol 2003;(4):448-464
[20] Cohen JK. Highlights on the etiology of keloid [J].Surg Forum,1971, 22(5): 488-496.
[21] Coumans JV,Lin TT,et al. Axonal regeneration and functional recovery after complete spinal cord transaction in rats by delayed treatment with transplants and neurotrophins [J].J Neurosci,2001,21(23):9334-9344
[22]陈璧,贾赤宇,汤朝武,等.碱性成纤维细胞生长因子对增生性瘢痕的作用[J].中华普通外科杂志,2002,17(1):45-47.
[23] Rifkin DB, Moscatelli D, Bizik J,et al.Growth factor control of extracellular proteolysis. Cell Differ Dev, 1990, 32:313-318.
[24]盛志勇,郭振荣.主编.危重烧伤治疗与康复学.第1版:北京科学出版社,2000:388-390.
[25]李卫华,李德水,刘洪琪.增生性瘢痕成纤维细胞与正常皮肤成纤维细胞生长差异比较.武警医学院学报,2005,14(2):104-107.
[26] Duncan MR,Hasan A,Berman B.Pentoxitylline and interferons decrease type and procollagen mRNA levels in dermal fibroblasts: revidence for mediation by nuclear factor down-regulation J. Invest Dermatol,1995,104:282-286
[27] Bord WA, Noble NA. TGF-βin Kindney fibrosis:a target for gene therapy. Kidney Int.1997,51:1388-1396
[28]陈统一,张键.周围神经损伤与再生研究的回顾与展望.国外医学.骨科学分册.2004,25(5):259
[29] Tongs J, Rich k M .Diphenylpiperazines enhance regeneration after facial nerve injury. J Neurocyology, 1997, 26(5):339-347
[30] Oliveira AL, Risling M, Deckner M, et al. Neonatal sciatic nerve transection induces TUNEL labeling of neurons in the rat spinal cord and DRG.. Neuroreport, 1997,8 : 2837-2840.
[31] Thompson CB. Apoptosis in the pathogenesis and treatment of disease. Science, 1995,267: 1456-1462.
[32] Lo AC, Houenou LJ, Oppenheim RW. Apoptosis in the nervous system: morphological features, methods, pathology, and prevention.Arch Histol Cytol,1995, 58:139-149.
[33]蔡文琴,阮怀珍,黎海蒂.医用神经生物学基础[M]重庆:西南师范大学出版社,2001:41,416-420
[34] Ernfors P, Nuclear factor-Kb to rescue of cytokine-induced neuronal survival. JCB, 2000,148:223-225
[35] Brushart TM, Mesulam MM. Alteration in connection between muscle and anterior horn motoneurons after peripheral nerve repair. Science, 1980;208(9):603
[36] Wikholm RP, Swett JE, Torigoe Y, et al. Repair of severed peripheral nerve: A superior anatomic and functional recovery with a new“reconnection" technique. Otolaryngol Head Neck Surg, 1988;99(4):353
[37] Gilmour JA, Myles LM, Glasby MA. The fate of motoneurons in the spinal cord after peripheral nerve repair: A quantitative study using the neural tracer horseradish peroxidase. J Neurosurg, 1995;82(4):623
[38] Fernandez E, Pallini R, Marchese E, et al. Quantitative, morphological, and somatotopic nuclear changes after facial nerve regeneration in adult rats: A possible challenge to the“no new neurons" dogma. Neurosurg, 1995;37(3):456
[39]杨抚华主编.医学细胞生物学概论第三版.成都:四川科学技术出版社,1996,157.
[40] Femandes KJL,Da-Peng Fan,Tsui BJ,et a1.Influence of the axotomy to cell bodydistance in rat rubrospinal and spinal motoneurons:differential regulation of GAP- 43. tubulins,and neurofilament. J Comp Neurol,1999,414(4):495-510.
[41] A.Lasorella,J.Stegmuller,D.Guardavaeearo,et al. Degradation of Id2 by the anaphase- promoting complex couples cell cycle exit and axonal growth. Nature,2006,442:471-474
[42] Kwswani SC, Rosenberg B, Hoke A. The use of GAP-43 mRNA quantification in high throughput screening of putative neuroprotective agents in dorsal root ganglion cultures. J Neurosci Methods. 2004;136(2):193-195
[43] Gupta SK,Mishra R, Kusum S, et al .GAP-43 is essential for the neutrophic effects of BDNF and positive AMPA receptor modulator S 18986.Cell Death Differ.2009; 16(4): 624-637
[44] Monnier PP, Sierra A, Schwab JM, et al. The Rho/ROCK pathway mediates neurite growth-inhibitory activity associated with the chondroitin sulfate proteoglycans of the CNS glial scar [J].Mol Cell Neurosci,2003,22:319-330
[45] Krenz NR,WraverL C.Effect of spinal cord transaction on N-Methyl-D-Aspartate receptors in the cord. J Neurotrauma,1998,15:1027-1036
[46] Me-Conkey DJ,Sten O. The role of calcium in the regeneration of apoptosis. J Leukoe Biol,1996,59:775-782
[47] Weikert S etal.Rapid dependent No-production from central nervous system cells in culture measured by NO-nitrite/ozone chemolinescene. Brain Res,1997,748:1-11
[48] GuY,SpasieZ,WuW.The effects of remaining axons on motorneuron Survival and NOS expression following axotomy in adult rats. Dev Neurosi,1997,19:255-259
[49] Waris T.Rechardt L,Kyosola K.Reinnervation of human skin grafts:A histochemical study.Plast Reconstr,Surg.1983,72:439-440
[50]夏保芦,杨敏,张艳,等.大鼠脊髓、脑干和海马乙酰胆碱酯酶活性的研究.中国组织化学与细胞化学杂志,2000,9(4):450-420
[51] Nakamura Hubschmann OR,Nathanson De .The role of calcium and cellular membrane dysfunction in experimental trauma and subarachnoid hemorrhage.J Neurosurg,1985,62: 698-703
[52] Krizba I,Joo F,Pestean A,et a1.Localization and biochemical characterization of acid phosphatase isoforms in the olfactory system of adult rats.Neuroscience.1997,76 (3):799-807
[53] Chen ZY,Chai YF,Cao L,et al.Glial cell line-derived neurotrophic factor enchances axonal regeneration following sciatic nerve transaction in adult rats [J] .Brain Res,2001;902(2):272-276.
[54] Chen YS,Murakami S,Gyo K,et al.Efects of basic fibroblast growth factor (bFGF)- neutralizing antibody and platelet factor 4 on facial nerve regeneration[J] . Exp Neurol,1999;155(2):274-283.
[55] Kerekes N,Landry M,Lundmark K,et al.Efect of NGF,BDNF,bFGF,aFGF and cell density on NPY expression in cultured rat dorsal root ganglion neurones[J].J Auton Nerv Syst,2000;81(13):128-138.
[56] Eric J. Nesstler, Stever E, Hyman, Robert C. Molecular Neuropharmacology. A Foundation for Clinical Neuroscience,2001, 235-252.
[57]王廷华.NGF ,BDNF,NT-3, GDNF在背根节不同神经元的免疫组织化学证据.[J]神经解剖学杂志.2001,5(1):23-25
[58]舒冰,周重建,马迎辉等.神经营养因子在周围神经再生过程中的作用[J]安徽医药2006, 10 (9):641-643
[59] Krekoski CA.Attenuation and recovery of nerve growth factor receptor mRNA in dorsal root qang lion neurons following axtomy.J Neuroscl Res 1996;43(1):1-11
[60]尹方明.P75和TrKA两种NGF受体系[J]国外医学神经病学神经外科学分册,1997,24(4):205-207
[61]孙凤艳主编.医学神经生物学.上海科技出版社.2008:212-213
[62] Xin Wang, Bauer JB, Yong L i, et al. Characterization of a p75NTR apoptotic signaling pathway using a novel cellular model[J ]. J BiolChem , 2001, 276 (36)∶33812.
[63] Johnson EM,Taniuchi M,Distefano P S.Expression and possible function of nerve growth factor receptors on Schwann cells[J].Trends Neurosei,1988,11(7)299-304
[64] Gaiko MJ.Tessier- lavigne M.Function of an axonal chemoattractant modulated by metalloprotease activity [J].Science, 2000, 289(5483): 1365.
[65] Gage FH.Mammalian neural stem[J].Science,2000,287:1433-1438
[66] Levi-Montalcini R. The nerve growth factor 35years late[J]r. Science.1987 ,237:1154
[67] Lipps BV.Isocation of nerve growth factor(NGF) from human body fluid;saliva,serumaand urine;comparison between cobra venom and cobra serm NGF.J Nat Toxins 2000;9 (4):349-356
[68] Lipps BV.Isocation and characterization of nerve growth factor (NGF) excreted from caltured eukaryotic cell. NGF. [J]Nat Toxins 2001;10(3):213-219
[69] Snider WD, Johnson EM. Neurotrophic molecules .Annal Neurol , 1989 ,26:48.
[70] Rende M , Hagg T, M antho rpeM , et al. Nerve growth factor receptor immuno reactivity in neurons of the normal adult rat spinal cord and its modulation after peripheral nerve lesions. J Comp Neurol, 1992, 319: 285.
[71]张玉波,伍亚民,刘磊,等.NGF促再生周围神经中血管生成及其机制研究[J]. 2007,15(6):401-404
[72] Barde YA,Edger D,Thoenen H. Purification of a new neurotrophic factor from mammalian brain. EMBO [J],1982 ;1 (5):549
[73] Leibrock J , Lottspeich H , Hohn A et al .Molecular cloning and expression of brain- derived neurotrophic factor. Nature ,1989 ;341:149
[74] Marini AM,Jiang X,Wu X,et a1.Role of brain-derived neurotrophic factor and NF-kappaB in neuronal plasticity and survival:from genes to phenotype.[J]Rester Neurol Neurosci. 2004;22(2):121-130
[75]赖晓霏,骆文龙.神经营养因子在周围神经损伤后的作用.现代医药卫生,2008,12:1838-1839
[76] Leibrock , Lottspeich F, Hohn A. Molecular cloning and exp ression of brain - derived neurotrophic factor [ J ]. Nature, 341 (6238):149-155
[77] Friedman B, Kleinfeld D, IP NV , et al. BDNF and NT-4/5 exert neurotrophic influence on injured adult spinal motor neurons. J Neuro sci, 1995, 15: 1044-1056
[78] Binder DK, Scharfman HE. Brain-derived neurotrophic factor [J].Growth Factors, 2004, 22(3): 123.
[79] Barakat Walter I. Brain-derived neurotrophic factor like immunoreactivity is localized mainly in small sensory neurons of rat dorsal root ganglia. J Neurosci Methods1996 ;68 (2) :281
[80] Ernfors P, Lee KF. Mice lacking brain derived neurotrophic factor develop with sensory deficits. Nature, 1994; 368: 147
[81]倪师今,王廷华,陈彦红.外周支及中枢支切断对背根节BDNF和NT-3表达的影响华西医大学报.2001; 32 (3) : 350- 352
[82] Zhou XF , Chie ET , Deng YS , et al. Injured primary sensory neurons switch phenotype for brain-derived neurotrophic factor in the rat . Neuroscience , 1999 ; 92 (3) : 841-853
[83] Wu A, Moheni R, Ying Z.A saturated-fat diet aggrawates the outcome of traumatic brain injury on hippocampal plasticity and cognitive function by reducing brain- derived neurotrophic factor[J].Neuroscience,2003, 119: 365
[84] Novikova L,Novikov L,Kellerth JO. Effects of neurotransplants andBDNF on the survival and regeneration of injured adult spinal motoneurons. Eur J Neurosei.1997,9(12): 2774-277
[85] Menei P ,Montero - Menei C ,Whittemore SR , et al . Eur J Neurosci, 1998 ,10 (2) :607 - 621.
[86] Gravel C , Gotz R ,Zorrain A , et al . Adenoviral gene transfer of ciliary neurotrophic factor and brain-derived neurotrophic factor leads to long term survival of axotomized motor neurons [J]. Nature Medicine ,1997 ,3 (7) :765-770
[87] Patrik Ernfors , Carlos F. IbanezTed , Ebendal. Molecular cloning and neurotrophic activites of a protein with structural similarities to nerve growth factor : development and topographical expression in the brain . Proc Natl Acad Sci USA , 1990 ,87 :5454
[88] Maisonpiere P C , Belluscio L. Neurotrophin-3 : a neurotrophic gactor related to NGF and BDNG . Science,1990 ,247 :1446
[89] Ernfors P. Identification of cells in rat brain and peripheral tissues expressing mRNA for members of the nerve growth factor family.Neuron , 1990 ,5 :511
[90]杨宏,伯音,周长满.神经营养因子在小鼠脾的定位.解剖学报,1998 ,29 (4) :374
[91] Maisonpiene P. C . Human and rat brain-derived neurotrophic factors and neurotrophin-3 : gene structure ,distribution genomics ,and chromosomal localizations . Genomics ,1991 , 10 (3) :558
[92] Ockel M, Lewin G R ,Barde Y A . In vivo effects of neurotrophin-3 during sensory neurogenesis. Development , 1996 ,122 (1) :381
[93] Schell L, Schneider R, Kolbeck R, et al. Neurotrophin-3 enchances sprouting of corticospinal tract during development and after adult spinal cord lesion . Nature ,1994 ,367 :170
[94] Sendtmer M , Holtmann B , Hugnes R A . The response of motorneurons to neurotrophins. Neurochem Res ,1996 ,21 (7) :831
[95] Airaksineu M S,Meyer M . Most classes of dorsal root ganglion neurons are severely depleted but not absent in mice lacking neurotrophin-3. Neuroscience ,1996 ,73 (4) :907
[96]郭树章,任先军等.神经营养素-3对大鼠急性脊髓损伤后血中一氧化氮合成酶的影响.中国矫形外科杂志2005,11(22):1730-1732
[97] Schnell L. Neurotrophin-3 enhances sprouting of corticospinal tract during development and after adult spinal cord lesions see commtents [J ] . Nature , 1994 , 367 ( 6459) :170
[98] Malcangio M. Nerve growth factor increases stimulusevoked release of sensory neuropeptides in the rat spinal cord [ J ] . Eur J Neurosci ,1997 ,9 (5) :1101
[99] Blits B, Dijkkuizen P A, Boer GJ, et al. Intercostal nerve implants transduced with an adenoviral vector encoding neurotrophin-3 promote regrowth of injuried rat corticospinal tract fibers and improve hindlimb function . Exp Neurol , 2000 ,164 :25
[100]Lin L F, Doherty DH, Lile JD, et al.GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons[J]. Science ,1993 ,260 (5111) :1130-1132.
[101] Tupp M, Belluardo N,Funakoshl H,el a1.Complementary and overlapping expression of glial cell line-derived neurotrophi factor(GDNF),c-ret pinto-oncogene,and GDNF receptor-alpha indicates multiple mechanisms of trophic actions in the adult rat CNS[J].J Neurosci,1997,17:3554-3567.
[102]袁源,杨志敏,王廷华,等.GDNF的研究进展.神经解剖学杂志,2003,19(1):103-108.
[103]Henderson CE,Philips HS,Pollock RA,et al. GDNF: A potent survival factor for motoneurons present in peripheral nerve and muscle. Science,1994, 266:1062-1066
[104]Saarma M. GDNFαstranger in the TGF-beta superfamily[J].Eur J Biochem ,2000 ,267 (24) :6968-6971.
[105]Bar KJ, Saldanha GJ, Kennedy AJ, et al.GDNF and its receptor component Ret in injured human nerves and dorsal root ganglia. Neuroreport ,1998,9:43-47
[106]Naveihan P,Elshamy WM,Ernfors P.Differential regulation of mRNAs for GDNF and its receptors Ret and GDNFR alpha after sciatic nerve lesion in the mouse.Eur J Neurosci, 1997,9:1450-1460
[107]Watabe K, Sakamoto T, et al. Adenoviral gene transfer of glial cell line-derived neurotrophic factor to injured adult motoneurons [ J ] .Hum Cell , 2001 ,14 (1) :7.
[108]Li L, Wu W, Lin LF, et al. Rescue of adult mouse motoneurons from injury-induced cell death by glial cell line-derived neurotrophic factor.Proc Natl Acad Sci USA,1995, 92:9771-9775
[109]Wong BJ F, Crmley RL. Nerve wound healing. Wound healing for the otolaryngologist- head and neck surgeon, 1995 ;28:881
[110]Sendtner M , Arakawa Y, St?ckli KA , et al. Effect of ciliary neurotrophic factor( CNTF) on motoneuron survival [J ].J Cell Sci Suppl ,1991 ,15 :103-1091
[111]Adler R. Ciliary neurotrophic factor as an injure factor. Current Opinion in Neurobiology , 1993 ;3∶785
[112]柳鹏,赵庆杰.外源性NGF对坐骨神经损伤后脊髓前角细胞CNTF表达的影响[ J ].哈尔滨医科大学学报, 2004, 38 (1) : 51-53.
[113]Zhang J, Lineaweaver WC, Oswald T, et al. Ciliary neurotrophic factor for acceleration of peripheral nerve regeneration: an experiment study [J]. J Reconstr Microsurg, 2004, 20 (4) : 323– 327
[114]许家军,陈尔瑜,路长林,等.重组睫状神经营养因子对周围神经再生中多种细胞的作用[ J ].神经解剖学杂志, 2002, 18 ( 4) :355 - 357
[115]Bradford M.M.A Rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.Anal Biochem. 1976, 72,248-254
[116]Riley DA,Land DH. .Can bomieanhydrase activity of human peripheral nerve:a possible histochermiealaidto nerve repair. J Hand Sury.1984,9(1):112-120.
[117]Rydevik M, Bergstrom F, Mitts C, Danielson N. Locally-applied collagenase and regeneration of transected and repaired rat sciatic nerves [J]. J Plast Reconstr Surg Hand Surg 2002; 36:193-196
[118]Smith X, van Neck JW, A foke A, et al. Reduction of neural adhesions by biodegradable autocross linked hyaluronic acid gel after injury of peripheral nerves: an experimental study [J]. J Neurosurg, 2004, 101:648-652
[119]Xu J, Varitim idis SE, Fisher KJ, et al. The effect of wrapping scarred nerves with autogenous vein graft to treat recurrent chronic nerve compression [J]. J Hand Surg (Am),2000, 25: 93-103
[120]Gorgulu A, Uzal C, Doanay L, et al The effect of low-dose external beam radiation on extraneural scarring after peripheral nerve surgery in rats [J]. Neurosurgery, 2003, 53:1389-1396
[121]Shellswell GB, Restall DJ, et al. Identification and differential distribution of collagen types in the central and peripheral nervous system [J]. Febs Lett,1979, 106:305～31
[122]付小兵,王正国主编.现代高新技术与创伤修复[M].人民军医出版社2002,5
[123]陈振兵,洪光祥,王发斌.大鼠坐骨神经损伤后神经内膜Ⅰ、Ⅲ型胶原含量的变化,中华显微外科杂志1997,20(2):53
[124]Ian R.P.Michael J.B.Susan R.R.Susan E.Effect of tension on nerve regeneration in rat sciatic nerve transection model Annals of Plastic Surgery. 2004,53(4):1688-1693
[125]Robert S. Shahin Z. Rudolf H,et al.Alleviated tension at the repair site enhances functional regeneration: the effect of full range of motion mobilization on the regeneration of peripheral nerves-histological,electro physiologic and functional results in a rat mode. Trauma 2004; 56 (3): 571-584
[126]Lewin GR, Barde YA.Physiology of the neurotrophins [J].Annu Rev Neurosci,1996, 19:289-317
[127]Nakamura M,Fujimura Y,Yato Y,etal. Changes in choline acetyltransferase activity and distribution following in incomplete cervieal spinal cord injury in the rat.Neuroseienee,1996,75:481
[128]朱悦,包峰,王星铎.大鼠脊髓不完全性损伤后前角运动神经元的酶细胞化学改变.中国组织化学与细胞化学杂志,1999,8(2):173-76
[129]DE·Duvo, C.Lysosame .A new group of cytoplasmic particles in subcellular particles. [J].The Ronald press, 1995, 26:33
[130]刘红光,洪光祥,王发斌,等.胚胎枝芽提取物对周围神经损伤后脊髓腹角运动神经元的保护作用.中华创伤杂志,1998,14:223-225
[131]庞清江,罗永湘,房清敏.神经生长因子对脊髓运动神经元的保护作用.中华手外科杂志,1997,13:19-21
[132]Aldskogius H,Arvidsson J,Grant G. The reaction of primary sensory neurons to peripheral nerve injury with particular emphasis on transganglionic change. Brain Res,1985;357(1):27-46
[133]Kledanoff ST. Oxygen metabolism and toxic properties of phagocytes. Ann Int Med,1980;93:480-484
[134]庞清江,罗永湘,毛宾尧.坐骨神经损伤致脊髓前角运动元内酶学变化实验研究的初步报道.中国矫形外科杂志,1996,2:290.
[135]Curits R, Adryan KH Zhu Y, etal.Retrograde axonal transport of CNFT is inereased by peripheral nerve injury. Natrue. 1993, 365:253-255
[136]Rossi C, Angelucci A, Costantin L, et al. Brain-derived neurotrophic Factor (BDNF) is required for the enhancement of hippocampal neurogenesis following environmental enrichment [J].Eur J Neurosci, 2006,24(7): 1850
[137]Rose CR, Blum R, Kafitz KW, et al. From modulator to mediator: rapid effects of BDNF on ion channels [J].Bioessays, 2004, 26(11):1185.
[138]Shirley DM, Williams SA, Santos PM. Brain-derived neurotrophic factor and peripheral nerve regeneration: A function evaluation [J].Laryngoscope.1996,106:629-632
[139]Doughety KD, Dreyfus CF, Black IB. Brain-derived neurotmphic factor in astrocytes oligedendrocyte and microglia macrophages after spinal cord injury[J].Neurobiol, 2000, 7(6): 574.
[140]Snyder SK,Bymes KR,Borke RC,et al.Quantitation of calcitonin-gene-related peptide mRNA and neuronal cell death in facial motor nucleus following axotomy and 633nm low power laser treatment.Lasers SurgMed.2002:31(3):216-222.
[141]Eberhardt KA,Irintchev A,Al-Majed AA,et al. BDNF/TrkB signaling regulates HNK-l Carbohydrate expression in regenerating motornerves and promotes functional recovery after peripheral nerve repair.Exp Neurol.2006: 198(2): 500-510
[142]Marcolw, Kotulska K, Larysz, et al. Extracts obtained from predegenerated nerves improve functional recovery after sciatic nerve transection [J]. Microsurgery, 2005; 25(6): 486- 494.
[2] Keith F,Tessa G.Axonal regeneration in the peripheral and central nervous systems- current issues and advances [J].J Neurol Sci,2004,31:142-156
[3] Torigoe K, Hashimoto K, Lundborg G. A role of migratory Schwann cells in a conditioning effect of peripheral nerve regeneration [J]. Exp Neurol,1999,160(1):99-108.
[4] Somkova I,Krieglstein J.Neuroprotection mediated via neurotrophic factors and induction of neurotrophic factors[J]. Brain Res Rev,1999,30(2):176-188.
[5] Frostick SP,Yin Q,Kemp GJ.Schwann cells,neurotrophic factors and peripheral nerve regeneration [J].Microsurgery,1998,l8(7):397-405.
[6] Neuberger TJ,CeVries GH.Distribution of fibroblast growth factor in cultured dorsal root ganglion neurons and Schwann cells localization during maturation in vitro[J].J Neurocytol,1993,22(6):436-448.
[7] Dubovy P.Schwann cells and endconeurial extracellular matrix molecules as potential cues for sorting of regenerated axons[J].Anat Soi Int,2004,79(4):198-208
[8] Li X,Lynn BD,Olson C,et al.Connexin29 expression,immunocytochemistry and freeze- fracture replica immunogold labeling (FRIL)in sciatic nerve.Eur J Neurosci.2002, 16:795-806
[9] Dezawa M,Mutoh T,Dezawa A,et al.Putative gap junctional communication between axon and regenerating Schwann cells during mammalian peripheral nerve regeneration. Neuroscience,1998,85:663-667.
[10] Sieard RE.Differential inflammatory and immunological responses in tissue regeneration and repair [M].Ann N Y Acad Sci,2002,961:368-371
[11] Mantovani A,Sozzani S,Locati M,et a1.Macrophage polarization:Tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes[J].Trends Immune, 2002,23(11): 549-560
[12]李立钧,陈统一.周围神经损伤与再生中的细胞和细胞分子.国外医学:骨科学分册,2004,25(5):280-283.
[13] Akassoglou K,Yu WM,Akpinar P,et a1.Fibrin inhibits peripheral nerve remyelination by regulating Schwann cell differentiation [J].Neuron,2002,33(6):861-875
[14] Mligiliche N,Endo K,Okamoto K,et al. Extracellular matrix of human amion manufactured into tubes as conduits for peripheral nerve regeneration[J].J BiomedMater Res 2002; 63 (5): 591-600.
[15] Takeda Y ,Murakami Y ,Asou H,et a1.The roles of cell adhesion molecules on the formation of peripheral myelin.Keio J Med,2001.50:240-248
[16] Fox GB,Kjoller C,Murphy K J,et al.The modulations of NCAM polysialylation state that follow transient global ischemia are brief on neurons but enduring on glia. J Neuropathol Exp Neurol,2001,60(2):132-140
[17] Paddok HN, Schultz GS, Barker HV,et al.Analysis of gene expression patterns in human postburn hypertrophic scars .J Bum Care Rehbil 2003;24(6):371-377
[18]陈中伟主编.周围神经损伤基础与临床研究.人民卫生出版社,1996:120-135
[19] Stamenkovic I,Extracellular matric remodeling :the role of matric metalloprtenases Pathol 2003;(4):448-464
[20] Cohen JK. Highlights on the etiology of keloid [J].Surg Forum,1971, 22(5): 488-496.
[21] Coumans JV,Lin TT,et al. Axonal regeneration and functional recovery after complete spinal cord transaction in rats by delayed treatment with transplants and neurotrophins [J].J Neurosci,2001,21(23):9334-9344
[22]陈璧,贾赤宇,汤朝武,等.碱性成纤维细胞生长因子对增生性瘢痕的作用[J].中华普通外科杂志,2002,17(1):45-47.
[23] Rifkin DB, Moscatelli D, Bizik J,et al.Growth factor control of extracellular proteolysis. Cell Differ Dev, 1990, 32:313-318.
[24]盛志勇,郭振荣.主编.危重烧伤治疗与康复学.第1版:北京科学出版社,2000:388-390.
[25]李卫华,李德水,刘洪琪.增生性瘢痕成纤维细胞与正常皮肤成纤维细胞生长差异比较.武警医学院学报,2005,14(2):104-107.
[26] Duncan MR,Hasan A,Berman B.Pentoxitylline and interferons decrease type and procollagen mRNA levels in dermal fibroblasts: revidence for mediation by nuclear factor down-regulation J. Invest Dermatol,1995,104:282-286
[27] Bord WA, Noble NA. TGF-βin Kindney fibrosis:a target for gene therapy. Kidney Int.1997,51:1388-1396
[28]陈统一,张键.周围神经损伤与再生研究的回顾与展望.国外医学.骨科学分册.2004,25(5):259
[29] Tongs J, Rich k M .Diphenylpiperazines enhance regeneration after facial nerve injury. J Neurocyology, 1997, 26(5):339-347
[30] Oliveira AL, Risling M, Deckner M, et al. Neonatal sciatic nerve transection induces TUNEL labeling of neurons in the rat spinal cord and DRG.. Neuroreport, 1997,8 : 2837-2840.
[31] Thompson CB. Apoptosis in the pathogenesis and treatment of disease. Science, 1995,267: 1456-1462.
[32] Lo AC, Houenou LJ, Oppenheim RW. Apoptosis in the nervous system: morphological features, methods, pathology, and prevention.Arch Histol Cytol,1995, 58:139-149.
[33]蔡文琴,阮怀珍,黎海蒂.医用神经生物学基础[M]重庆:西南师范大学出版社,2001:41,416-420
[34] Ernfors P, Nuclear factor-Kb to rescue of cytokine-induced neuronal survival. JCB, 2000,148:223-225
[35] Brushart TM, Mesulam MM. Alteration in connection between muscle and anterior horn motoneurons after peripheral nerve repair. Science, 1980;208(9):603
[36] Wikholm RP, Swett JE, Torigoe Y, et al. Repair of severed peripheral nerve: A superior anatomic and functional recovery with a new“reconnection" technique. Otolaryngol Head Neck Surg, 1988;99(4):353
[37] Gilmour JA, Myles LM, Glasby MA. The fate of motoneurons in the spinal cord after peripheral nerve repair: A quantitative study using the neural tracer horseradish peroxidase. J Neurosurg, 1995;82(4):623
[38] Fernandez E, Pallini R, Marchese E, et al. Quantitative, morphological, and somatotopic nuclear changes after facial nerve regeneration in adult rats: A possible challenge to the“no new neurons" dogma. Neurosurg, 1995;37(3):456
[39]杨抚华主编.医学细胞生物学概论第三版.成都:四川科学技术出版社,1996,157.
[40] Femandes KJL,Da-Peng Fan,Tsui BJ,et a1.Influence of the axotomy to cell bodydistance in rat rubrospinal and spinal motoneurons:differential regulation of GAP- 43. tubulins,and neurofilament. J Comp Neurol,1999,414(4):495-510.
[41] A.Lasorella,J.Stegmuller,D.Guardavaeearo,et al. Degradation of Id2 by the anaphase- promoting complex couples cell cycle exit and axonal growth. Nature,2006,442:471-474
[42] Kwswani SC, Rosenberg B, Hoke A. The use of GAP-43 mRNA quantification in high throughput screening of putative neuroprotective agents in dorsal root ganglion cultures. J Neurosci Methods. 2004;136(2):193-195
[43] Gupta SK,Mishra R, Kusum S, et al .GAP-43 is essential for the neutrophic effects of BDNF and positive AMPA receptor modulator S 18986.Cell Death Differ.2009; 16(4): 624-637
[44] Monnier PP, Sierra A, Schwab JM, et al. The Rho/ROCK pathway mediates neurite growth-inhibitory activity associated with the chondroitin sulfate proteoglycans of the CNS glial scar [J].Mol Cell Neurosci,2003,22:319-330
[45] Krenz NR,WraverL C.Effect of spinal cord transaction on N-Methyl-D-Aspartate receptors in the cord. J Neurotrauma,1998,15:1027-1036
[46] Me-Conkey DJ,Sten O. The role of calcium in the regeneration of apoptosis. J Leukoe Biol,1996,59:775-782
[47] Weikert S etal.Rapid dependent No-production from central nervous system cells in culture measured by NO-nitrite/ozone chemolinescene. Brain Res,1997,748:1-11
[48] GuY,SpasieZ,WuW.The effects of remaining axons on motorneuron Survival and NOS expression following axotomy in adult rats. Dev Neurosi,1997,19:255-259
[49] Waris T.Rechardt L,Kyosola K.Reinnervation of human skin grafts:A histochemical study.Plast Reconstr,Surg.1983,72:439-440
[50]夏保芦,杨敏,张艳,等.大鼠脊髓、脑干和海马乙酰胆碱酯酶活性的研究.中国组织化学与细胞化学杂志,2000,9(4):450-420
[51] Nakamura Hubschmann OR,Nathanson De .The role of calcium and cellular membrane dysfunction in experimental trauma and subarachnoid hemorrhage.J Neurosurg,1985,62: 698-703
[52] Krizba I,Joo F,Pestean A,et a1.Localization and biochemical characterization of acid phosphatase isoforms in the olfactory system of adult rats.Neuroscience.1997,76 (3):799-807
[53] Chen ZY,Chai YF,Cao L,et al.Glial cell line-derived neurotrophic factor enchances axonal regeneration following sciatic nerve transaction in adult rats [J] .Brain Res,2001;902(2):272-276.
[54] Chen YS,Murakami S,Gyo K,et al.Efects of basic fibroblast growth factor (bFGF)- neutralizing antibody and platelet factor 4 on facial nerve regeneration[J] . Exp Neurol,1999;155(2):274-283.
[55] Kerekes N,Landry M,Lundmark K,et al.Efect of NGF,BDNF,bFGF,aFGF and cell density on NPY expression in cultured rat dorsal root ganglion neurones[J].J Auton Nerv Syst,2000;81(13):128-138.
[56] Eric J. Nesstler, Stever E, Hyman, Robert C. Molecular Neuropharmacology. A Foundation for Clinical Neuroscience,2001, 235-252.
[57]王廷华.NGF ,BDNF,NT-3, GDNF在背根节不同神经元的免疫组织化学证据.[J]神经解剖学杂志.2001,5(1):23-25
[58]舒冰,周重建,马迎辉等.神经营养因子在周围神经再生过程中的作用[J]安徽医药2006, 10 (9):641-643
[59] Krekoski CA.Attenuation and recovery of nerve growth factor receptor mRNA in dorsal root qang lion neurons following axtomy.J Neuroscl Res 1996;43(1):1-11
[60]尹方明.P75和TrKA两种NGF受体系[J]国外医学神经病学神经外科学分册,1997,24(4):205-207
[61]孙凤艳主编.医学神经生物学.上海科技出版社.2008:212-213
[62] Xin Wang, Bauer JB, Yong L i, et al. Characterization of a p75NTR apoptotic signaling pathway using a novel cellular model[J ]. J BiolChem , 2001, 276 (36)∶33812.
[63] Johnson EM,Taniuchi M,Distefano P S.Expression and possible function of nerve growth factor receptors on Schwann cells[J].Trends Neurosei,1988,11(7)299-304
[64] Gaiko MJ.Tessier- lavigne M.Function of an axonal chemoattractant modulated by metalloprotease activity [J].Science, 2000, 289(5483): 1365.
[65] Gage FH.Mammalian neural stem[J].Science,2000,287:1433-1438
[66] Levi-Montalcini R. The nerve growth factor 35years late[J]r. Science.1987 ,237:1154
[67] Lipps BV.Isocation of nerve growth factor(NGF) from human body fluid;saliva,serumaand urine;comparison between cobra venom and cobra serm NGF.J Nat Toxins 2000;9 (4):349-356
[68] Lipps BV.Isocation and characterization of nerve growth factor (NGF) excreted from caltured eukaryotic cell. NGF. [J]Nat Toxins 2001;10(3):213-219
[69] Snider WD, Johnson EM. Neurotrophic molecules .Annal Neurol , 1989 ,26:48.
[70] Rende M , Hagg T, M antho rpeM , et al. Nerve growth factor receptor immuno reactivity in neurons of the normal adult rat spinal cord and its modulation after peripheral nerve lesions. J Comp Neurol, 1992, 319: 285.
[71]张玉波,伍亚民,刘磊,等.NGF促再生周围神经中血管生成及其机制研究[J]. 2007,15(6):401-404
[72] Barde YA,Edger D,Thoenen H. Purification of a new neurotrophic factor from mammalian brain. EMBO [J],1982 ;1 (5):549
[73] Leibrock J , Lottspeich H , Hohn A et al .Molecular cloning and expression of brain- derived neurotrophic factor. Nature ,1989 ;341:149
[74] Marini AM,Jiang X,Wu X,et a1.Role of brain-derived neurotrophic factor and NF-kappaB in neuronal plasticity and survival:from genes to phenotype.[J]Rester Neurol Neurosci. 2004;22(2):121-130
[75]赖晓霏,骆文龙.神经营养因子在周围神经损伤后的作用.现代医药卫生,2008,12:1838-1839
[76] Leibrock , Lottspeich F, Hohn A. Molecular cloning and exp ression of brain - derived neurotrophic factor [ J ]. Nature, 341 (6238):149-155
[77] Friedman B, Kleinfeld D, IP NV , et al. BDNF and NT-4/5 exert neurotrophic influence on injured adult spinal motor neurons. J Neuro sci, 1995, 15: 1044-1056
[78] Binder DK, Scharfman HE. Brain-derived neurotrophic factor [J].Growth Factors, 2004, 22(3): 123.
[79] Barakat Walter I. Brain-derived neurotrophic factor like immunoreactivity is localized mainly in small sensory neurons of rat dorsal root ganglia. J Neurosci Methods1996 ;68 (2) :281
[80] Ernfors P, Lee KF. Mice lacking brain derived neurotrophic factor develop with sensory deficits. Nature, 1994; 368: 147
[81]倪师今,王廷华,陈彦红.外周支及中枢支切断对背根节BDNF和NT-3表达的影响华西医大学报.2001; 32 (3) : 350- 352
[82] Zhou XF , Chie ET , Deng YS , et al. Injured primary sensory neurons switch phenotype for brain-derived neurotrophic factor in the rat . Neuroscience , 1999 ; 92 (3) : 841-853
[83] Wu A, Moheni R, Ying Z.A saturated-fat diet aggrawates the outcome of traumatic brain injury on hippocampal plasticity and cognitive function by reducing brain- derived neurotrophic factor[J].Neuroscience,2003, 119: 365
[84] Novikova L,Novikov L,Kellerth JO. Effects of neurotransplants andBDNF on the survival and regeneration of injured adult spinal motoneurons. Eur J Neurosei.1997,9(12): 2774-277
[85] Menei P ,Montero - Menei C ,Whittemore SR , et al . Eur J Neurosci, 1998 ,10 (2) :607 - 621.
[86] Gravel C , Gotz R ,Zorrain A , et al . Adenoviral gene transfer of ciliary neurotrophic factor and brain-derived neurotrophic factor leads to long term survival of axotomized motor neurons [J]. Nature Medicine ,1997 ,3 (7) :765-770
[87] Patrik Ernfors , Carlos F. IbanezTed , Ebendal. Molecular cloning and neurotrophic activites of a protein with structural similarities to nerve growth factor : development and topographical expression in the brain . Proc Natl Acad Sci USA , 1990 ,87 :5454
[88] Maisonpiere P C , Belluscio L. Neurotrophin-3 : a neurotrophic gactor related to NGF and BDNG . Science,1990 ,247 :1446
[89] Ernfors P. Identification of cells in rat brain and peripheral tissues expressing mRNA for members of the nerve growth factor family.Neuron , 1990 ,5 :511
[90]杨宏,伯音,周长满.神经营养因子在小鼠脾的定位.解剖学报,1998 ,29 (4) :374
[91] Maisonpiene P. C . Human and rat brain-derived neurotrophic factors and neurotrophin-3 : gene structure ,distribution genomics ,and chromosomal localizations . Genomics ,1991 , 10 (3) :558
[92] Ockel M, Lewin G R ,Barde Y A . In vivo effects of neurotrophin-3 during sensory neurogenesis. Development , 1996 ,122 (1) :381
[93] Schell L, Schneider R, Kolbeck R, et al. Neurotrophin-3 enchances sprouting of corticospinal tract during development and after adult spinal cord lesion . Nature ,1994 ,367 :170
[94] Sendtmer M , Holtmann B , Hugnes R A . The response of motorneurons to neurotrophins. Neurochem Res ,1996 ,21 (7) :831
[95] Airaksineu M S,Meyer M . Most classes of dorsal root ganglion neurons are severely depleted but not absent in mice lacking neurotrophin-3. Neuroscience ,1996 ,73 (4) :907
[96]郭树章,任先军等.神经营养素-3对大鼠急性脊髓损伤后血中一氧化氮合成酶的影响.中国矫形外科杂志2005,11(22):1730-1732
[97] Schnell L. Neurotrophin-3 enhances sprouting of corticospinal tract during development and after adult spinal cord lesions see commtents [J ] . Nature , 1994 , 367 ( 6459) :170
[98] Malcangio M. Nerve growth factor increases stimulusevoked release of sensory neuropeptides in the rat spinal cord [ J ] . Eur J Neurosci ,1997 ,9 (5) :1101
[99] Blits B, Dijkkuizen P A, Boer GJ, et al. Intercostal nerve implants transduced with an adenoviral vector encoding neurotrophin-3 promote regrowth of injuried rat corticospinal tract fibers and improve hindlimb function . Exp Neurol , 2000 ,164 :25
[100]Lin L F, Doherty DH, Lile JD, et al.GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons[J]. Science ,1993 ,260 (5111) :1130-1132.
[101] Tupp M, Belluardo N,Funakoshl H,el a1.Complementary and overlapping expression of glial cell line-derived neurotrophi factor(GDNF),c-ret pinto-oncogene,and GDNF receptor-alpha indicates multiple mechanisms of trophic actions in the adult rat CNS[J].J Neurosci,1997,17:3554-3567.
[102]袁源,杨志敏,王廷华,等.GDNF的研究进展.神经解剖学杂志,2003,19(1):103-108.
[103]Henderson CE,Philips HS,Pollock RA,et al. GDNF: A potent survival factor for motoneurons present in peripheral nerve and muscle. Science,1994, 266:1062-1066
[104]Saarma M. GDNFαstranger in the TGF-beta superfamily[J].Eur J Biochem ,2000 ,267 (24) :6968-6971.
[105]Bar KJ, Saldanha GJ, Kennedy AJ, et al.GDNF and its receptor component Ret in injured human nerves and dorsal root ganglia. Neuroreport ,1998,9:43-47
[106]Naveihan P,Elshamy WM,Ernfors P.Differential regulation of mRNAs for GDNF and its receptors Ret and GDNFR alpha after sciatic nerve lesion in the mouse.Eur J Neurosci, 1997,9:1450-1460
[107]Watabe K, Sakamoto T, et al. Adenoviral gene transfer of glial cell line-derived neurotrophic factor to injured adult motoneurons [ J ] .Hum Cell , 2001 ,14 (1) :7.
[108]Li L, Wu W, Lin LF, et al. Rescue of adult mouse motoneurons from injury-induced cell death by glial cell line-derived neurotrophic factor.Proc Natl Acad Sci USA,1995, 92:9771-9775
[109]Wong BJ F, Crmley RL. Nerve wound healing. Wound healing for the otolaryngologist- head and neck surgeon, 1995 ;28:881
[110]Sendtner M , Arakawa Y, St?ckli KA , et al. Effect of ciliary neurotrophic factor( CNTF) on motoneuron survival [J ].J Cell Sci Suppl ,1991 ,15 :103-1091
[111]Adler R. Ciliary neurotrophic factor as an injure factor. Current Opinion in Neurobiology , 1993 ;3∶785
[112]柳鹏,赵庆杰.外源性NGF对坐骨神经损伤后脊髓前角细胞CNTF表达的影响[ J ].哈尔滨医科大学学报, 2004, 38 (1) : 51-53.
[113]Zhang J, Lineaweaver WC, Oswald T, et al. Ciliary neurotrophic factor for acceleration of peripheral nerve regeneration: an experiment study [J]. J Reconstr Microsurg, 2004, 20 (4) : 323– 327
[114]许家军,陈尔瑜,路长林,等.重组睫状神经营养因子对周围神经再生中多种细胞的作用[ J ].神经解剖学杂志, 2002, 18 ( 4) :355 - 357
[115]Bradford M.M.A Rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.Anal Biochem. 1976, 72,248-254
[116]Riley DA,Land DH. .Can bomieanhydrase activity of human peripheral nerve:a possible histochermiealaidto nerve repair. J Hand Sury.1984,9(1):112-120.
[117]Rydevik M, Bergstrom F, Mitts C, Danielson N. Locally-applied collagenase and regeneration of transected and repaired rat sciatic nerves [J]. J Plast Reconstr Surg Hand Surg 2002; 36:193-196
[118]Smith X, van Neck JW, A foke A, et al. Reduction of neural adhesions by biodegradable autocross linked hyaluronic acid gel after injury of peripheral nerves: an experimental study [J]. J Neurosurg, 2004, 101:648-652
[119]Xu J, Varitim idis SE, Fisher KJ, et al. The effect of wrapping scarred nerves with autogenous vein graft to treat recurrent chronic nerve compression [J]. J Hand Surg (Am),2000, 25: 93-103
[120]Gorgulu A, Uzal C, Doanay L, et al The effect of low-dose external beam radiation on extraneural scarring after peripheral nerve surgery in rats [J]. Neurosurgery, 2003, 53:1389-1396
[121]Shellswell GB, Restall DJ, et al. Identification and differential distribution of collagen types in the central and peripheral nervous system [J]. Febs Lett,1979, 106:305～31
[122]付小兵,王正国主编.现代高新技术与创伤修复[M].人民军医出版社2002,5
[123]陈振兵,洪光祥,王发斌.大鼠坐骨神经损伤后神经内膜Ⅰ、Ⅲ型胶原含量的变化,中华显微外科杂志1997,20(2):53
[124]Ian R.P.Michael J.B.Susan R.R.Susan E.Effect of tension on nerve regeneration in rat sciatic nerve transection model Annals of Plastic Surgery. 2004,53(4):1688-1693
[125]Robert S. Shahin Z. Rudolf H,et al.Alleviated tension at the repair site enhances functional regeneration: the effect of full range of motion mobilization on the regeneration of peripheral nerves-histological,electro physiologic and functional results in a rat mode. Trauma 2004; 56 (3): 571-584
[126]Lewin GR, Barde YA.Physiology of the neurotrophins [J].Annu Rev Neurosci,1996, 19:289-317
[127]Nakamura M,Fujimura Y,Yato Y,etal. Changes in choline acetyltransferase activity and distribution following in incomplete cervieal spinal cord injury in the rat.Neuroseienee,1996,75:481
[128]朱悦,包峰,王星铎.大鼠脊髓不完全性损伤后前角运动神经元的酶细胞化学改变.中国组织化学与细胞化学杂志,1999,8(2):173-76
[129]DE·Duvo, C.Lysosame .A new group of cytoplasmic particles in subcellular particles. [J].The Ronald press, 1995, 26:33
[130]刘红光,洪光祥,王发斌,等.胚胎枝芽提取物对周围神经损伤后脊髓腹角运动神经元的保护作用.中华创伤杂志,1998,14:223-225
[131]庞清江,罗永湘,房清敏.神经生长因子对脊髓运动神经元的保护作用.中华手外科杂志,1997,13:19-21
[132]Aldskogius H,Arvidsson J,Grant G. The reaction of primary sensory neurons to peripheral nerve injury with particular emphasis on transganglionic change. Brain Res,1985;357(1):27-46
[133]Kledanoff ST. Oxygen metabolism and toxic properties of phagocytes. Ann Int Med,1980;93:480-484
[134]庞清江,罗永湘,毛宾尧.坐骨神经损伤致脊髓前角运动元内酶学变化实验研究的初步报道.中国矫形外科杂志,1996,2:290.
[135]Curits R, Adryan KH Zhu Y, etal.Retrograde axonal transport of CNFT is inereased by peripheral nerve injury. Natrue. 1993, 365:253-255
[136]Rossi C, Angelucci A, Costantin L, et al. Brain-derived neurotrophic Factor (BDNF) is required for the enhancement of hippocampal neurogenesis following environmental enrichment [J].Eur J Neurosci, 2006,24(7): 1850
[137]Rose CR, Blum R, Kafitz KW, et al. From modulator to mediator: rapid effects of BDNF on ion channels [J].Bioessays, 2004, 26(11):1185.
[138]Shirley DM, Williams SA, Santos PM. Brain-derived neurotrophic factor and peripheral nerve regeneration: A function evaluation [J].Laryngoscope.1996,106:629-632
[139]Doughety KD, Dreyfus CF, Black IB. Brain-derived neurotmphic factor in astrocytes oligedendrocyte and microglia macrophages after spinal cord injury[J].Neurobiol, 2000, 7(6): 574.
[140]Snyder SK,Bymes KR,Borke RC,et al.Quantitation of calcitonin-gene-related peptide mRNA and neuronal cell death in facial motor nucleus following axotomy and 633nm low power laser treatment.Lasers SurgMed.2002:31(3):216-222.
[141]Eberhardt KA,Irintchev A,Al-Majed AA,et al. BDNF/TrkB signaling regulates HNK-l Carbohydrate expression in regenerating motornerves and promotes functional recovery after peripheral nerve repair.Exp Neurol.2006: 198(2): 500-510
[142]Marcolw, Kotulska K, Larysz, et al. Extracts obtained from predegenerated nerves improve functional recovery after sciatic nerve transection [J]. Microsurgery, 2005; 25(6): 486- 494.