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胶质细胞源性神经营养因子促进脊髓损伤修复的研究进展 第3页

更新时间:2014-12-26:  来源:毕业论文

胶质细胞源性神经营养因子促进脊髓损伤修复的研究进展 第3页

  3  GDNF临床应用需要解决的问题
   
  大量的实验证实GDNF对于SCI有着很强的修复作用,可以保护神经元细胞,促进轴突的再生,但目前GDNF治疗SCI仍处于临床前的实验阶段,要应用于临床应用还需要解决以下问题:(1)疗效问题,SCI目前临床上仍没有确切的治疗方法,所有的方法都停留在实验阶段,GDNF促进SCI修复的作用,体外实验和动物实验都已经证实,但哺乳动物,甚至人体内实验目前尚未有实验证实,这需要有进一步的实验来证实。单独使用GDNF治疗SCI疗效有限,联合其它方法更有临床应用前景;(2)安全问题,目前使用的外源性GDNF是重组的GDNF,作为治疗用药,其药代动力学、稳定性、溶解度、纯度等问题以及可能机体带来的副作用仍不确定,近期有实验表明外源性的GDNF,由于纯度等问题,可以使机体产生抗体,影响疗效,甚至会交叉反应,对抗自体生成的内源性的GDNF,对机体产生不良的影响[26];(3)剂量问题,GDNF浓度与轴突再生的做用非线性关系,在高浓度和低浓度时GDNF作用较弱[15]。甚至有研究表明超出剂量范围使用GDNF反而阻止外周损伤神经元轴突的生长[30]。

  GDNF促进SCI修复作用已经得到很多实验的证实,很多学者也采取了不同的途径对GDNF在治疗脊髓方面探索,取得了不少成果,但由于SCI的修复因素很多,单一使用GDNF无法完成SCI的完全修复,目前GDNF对SCI修复的研究还处于实验阶段。GDNF联合应用细胞移植、基因治疗、其他神经营养因子等方法治疗SCI将是今后研究SCI治疗的主要方向之一。
【参考文献】
    [1]Lin LF,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.

  [2]Farhi J,Ao A,Fisch B,et al.Glial cell linederived neurotrophic factor (GDNF) and its receptors in human ovaries from fetuses, girls,and women[J].Fertil Sterili,2009online.

  [3]Lucini C,Maruccio L,Facello B,et al.Cellular localization of GDNF and its GFRalpha1/RET receptor complex in the developing pancreas of cat[J].J Anat,2008,213(5):565-572.

  [4]Paratcha G,Ledda F.GDNFandGFRα: a versatile molecular complex for developing neurons[J].Trends Neurosci,2008,31(8):384-391.

  [5]Yoong LF,Wan G,Too HP,et al.GDNFinduced cell signaling and neurite outgrowths are differentially mediated by GFRalpha1 isoforms[J].Mol Cell Neurosci,2009,41(4):464-473.

  [6]Kao CH,Chen SH,Chio CC,et al.Exogenous administration of glial cell linederived neurotrophic factor improves recovery after spinal cord injury[J].Resuscitation,2008,77(3):395-400.

  [7]Sharma HS.Posttraumatic application of brainderived neurotrophic factor and gliaderived neurotrophic factor on the rat spinal cord enhances neuroprotection and improves motor function[J].Acta Neurochir Suppl,2006,96:329-334.

  [8]Grumbles RM,Sesodia S,Wood PM,et al.Neurotrophic factors improve motoneuron survival and function of muscle reinnervated by embryonic neurons[J].J Neuropathol Exp Neurol,2009,68(7):736-746.

  [9]Zhou HL,Yang HJ,Li YM,et al.Changes in glial cell linederived neurotrophic factor expression in the rostral and caudal stumps of the transected adult rat spinal cord[J].Neurochem Res,2008,33(5):927-937.

  [10]Zhang L,Ma Z,Smith GM,et al.GDNFenhanced axonal regeneration and myelination following spinal cord injury is mediated by primary effects on neurons[J].Glia,2009,57(11):1178-1191.

  [11]潘世鹏,刘强,吴斗.局部应用GDNF对脊髓前角运动神经元的保护作用研究[J].中国骨伤,2009,22(2):122-124.

  [12]Guzen FP,de Almeida,Leme RJ,et al.Glial cell linederived neurotrophic factor added to a sciatic nerve fragment grafted in a spinal cord gap ameliorates motor impairments in rats and increases local axonal growth[J].Restorative Neurol Neurosci,2009,27(1):1-16.

  [13]Annette Markus,Tushar D,Patel,William D.Snider.Neurotrophic factors and axonal growth[J].Curr Opin Neurobiol,2002,12(5):523-531.

  [14]Uwe Ernsberger.The role of GDNF family ligand signaling in the differentiation of sympathetic and dorsal root ganglion neurons[J].Cell Tissue Res,2008,333(3):353-371.

  [15]Charles D.Mills,Andrew J.Allchorne,Robert S.Griffin,et al.GDNF selectively promotes regeneration of injuryprimed sensory neurons in the lesioned spinal cord[J].Mol Cell Neurosci,2007,36(2):185-194.

  [16]Ronald Deumens,Guido C,Koopmans A,Elbert AJ,et al.Regeneration of descending axon tracts after spinal cord injury[J].Neurobiology,2005,77(1-2):57-89.

  [17]Chu TH,Li SY,Guo A,et al.Implantation of neurotrophic factortreated sensory nerve graft enhances survival and axonal regeneration of motoneurons after spinal root avulsion[J].J Neuropathol Exp Neurol,2009,68(1):94-101.

  [18]Busch SA,Silver J.The role of extracellular matrix in CNS regeneration[J].Curr Opin Neurobiol,2007,17(1):120-127.

  [19]Adler JE,Nico L,VandeVord P,et al.Modulation of neuropathic pain by a glialderived factor[J].Pain Medicine (Malden,Mass),2009,10(7):1229-1236.

  [20]Wang YC,Wu YT,Huang HY,et al.Sustained intraspinal delivery of neurotrophic factor encapsulated in biodegradable nanoparticles following contusive spinal cord injury[J].Biomaterials,2008,29(34):4546-4553.

  [21]Liu S,Bohl D,Blanchard S,et al.Combination of microsurgery and gene therapy for spinal dorsal root injury repair[J].Mol Ther,2009,17(6):992-1002.

  [22]Madduri S,Papaloizos M,Gander B,et al.Synergistic effect of GDNF and NGF on axonal branching and elongation in vitro[J].Neurosci Res,2009,65(1):88-97.

  [23]Tannemaat MR,Eggers R,Hendriks WT,et al.Differential effects of lentiviral vectormediated overexpression of nerve growth factor and glial cell linederived neurotrophic factor on regenerating sensory and motor axons in the transected peripheral nerve[J]. Eur J Neurosci,2008,28(8):1467-1479.

  [24]Eggers R,Hendriks WT,Tannemaat MR,et al.Neuroregenerative effects of lentiviral vector-mediated GDNF expression in reimplanted ventral roots[J].Mol Cell Neurosci,2008,39(1):105-117.

  [25]Zhou Z,Peng X,Fink DJ,et al.HSVmediated transfer of artemin overcomes myelin inhibition to improve outcome after spinal cord injury[J].Mol Ther,2009,17(7):1173-1179.

  [26]Ansorena E,Garbayo E,Lanciego JL,et al.Production of highly pure human glycosylated GDNF in a mammalian cell line[J].Int J Pharm,2009,online.

  [27]Li C,Li L,Zhe YC,et al.Olfactory ensheathing cells genetically modified to secrete GDNF to promote spinal cord repair[J].Brain,2004,127(Pt 3):535-549.

  [28]Lo WC,Hsu CH,Wu AT,et al.A novel cellbased therapy for contusion spinal cord injury using GDNFdelivering NIH3T3 cells with dual reporter genes monitored by molecular imaging[J].J Nucl Med,2008,49(9):1512-1519.

  [29]刘晓刚,邓宇斌,蔡辉,等.控释胶质细胞源性神经营养因子与骨髓间充质干细胞源性神经元样细胞移植对猴损伤脊髓髓鞘的修复[J].中国组织工程研究与临床康复,2009,13(32):6219-6222.

  [30]Dolbeare D,Houle JD.Restriction of axonal retraction and promotion of axonal regeneration by chronically injured neurons after intraspinal treatment with glial cell linederived neurotrophic factor(GDNF)[J].J Neurotrauma,2003,20(11):1251-1261.

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