脊髓损伤后神经营养因子及干细胞治疗对轴突再生的影响:国外基础和临床研究新进展(英文)

Effect of neurotrophic factor and stem cell therapy on axonal regeneration after spinal cord injury: Overseas progress in basic and clinical researches

背景:近几年国外学者在脊髓损伤的病理机制、损伤后神经元的保护、少突胶质细胞的再生及神经干细胞的移植治疗等研究方面取得了实质性地进展。介绍国外近10年来对脊髓损伤的新认识,最新研究成果及未来的科研和治疗方向。资料来源:应6用计算机检索Medline数据库1987-01/2006-10脊髓损伤的相关文章,限定文章语言种类为English,检索词为“脊髓损伤;神经干细胞;轴突;神经营养因子;动物模型”,进行不同组合,选出相关文章。资料选择:对资料进行初审,选择脊髓研究中的与神经干细胞及神经营养因子有关的研究文献查找全文。纳入标准:①脊髓损伤中以探讨其机制及新治疗方法的文章。②探讨脊髓损伤后轴突再生,生长锥作用,引导再生方向的靶点,突触再形成及功能重建的文章。③神经营养因子和内源性神经干细胞治疗的文章。排除标准:①未被SCI收录的文章,相类似的研究。②无英文摘要的文章。资料提炼:共收集到相关文献1166篇,按上述标准纳入101篇,实际采用61篇,脊髓损伤机制相关文献12篇,轴突再生相关文献14篇,增长锥作用相关文献8篇,少突胶质细胞相关文献8篇,神经干细胞相关文献7篇,神经生长因子相关文献12篇。其余文献均被排除。资料综合:①脊髓损伤功能恢复的基础:损伤的轴突再生及增长;轴突穿透损伤瘢痕区的能力;轴突朝着正确的靶区方向再生;轴突增长到一定程度后停止,终端形成突触,与神经元相接;神经传递功能重建及运动功能重新恢复。②脊髓损伤的神经病理分析:脊髓损伤后的原发性损害、继发性损害。③脊髓损伤的分子生物学机制包括3个方面:对于成年人中枢神经系统损伤后的神经元的发展、再生,神经元通路的建立起着重要的作用轴突增长锥;对轴突的再生起到抑制作用中枢神经系统髓鞘蛋白;细胞膜和细胞内信号传递。④脊髓损伤中起重要作用的细胞和因子:少突胶质细胞,白血病抑制因子和Minocycline,内源性神经干细胞。⑤脊髓损伤动物模型:最常使用的模型是全部离断、部分离断模型和挫伤模型。⑥脊髓损伤研究的前景:已经开始把动物实验中神经营养因子和神经干细胞治疗发现用于临床,如白血病抑制因子在国外已经开始临床Ⅳ期实验,对内源性神经干细胞的诱导调控增殖研究也已经越来越受到重视。结论:神经营养因子干预治疗及神经干细胞治疗使脊髓损伤后的功能恢复成为可能。进一步探讨神经营养因子引起轴突再生的机制,将是脊髓损伤研究领域的未来方向,了解引导调控神经干细胞的增殖和分化方向,将在修复脊髓损伤方面发挥巨大的作用。

BACKGROUND： Now, progress has been made in understanding the pathomechanisms, protection of injured neurons, regeneration of oligodendrocytes and transplantation of neural stem ceils. This paper is aimed to introduce the decade progression, latest research and novel therapies in the area of spinal cord injury internationally. DATA SOURCES： Related articles published from January 1987 to October 2006 were chosen from the America Medline Database, and the language was limited to English, with the search keywords of ＂spinal cord injury; neural stem cells; axon; neurotrophic factor and animal model＂. STUDY SELECTION： After the primary trial, the full versions of the articles related to neural stem cell and neurotrophic factor were reviewed according to the following criterias： ① experiments investigating the mechanisms and novel therapies of spinal cord injury. ②papers revealing the axon regeneration, function of growth cone, targets for inducting the regeneration direction as well as synapse and function rebuild. ③ papers reporting neurotrophic factor and endogenous stem cell therapies. Excluded criteria： ①papers with lower impact factor in SCI or studies with similar results.②papers without English abstract. DATA EXTRACTION： A total of 1 166 papers were found in Medline, 101 papers accord with the above criteria, 61 papers were cited in this review, including 12 papers for the mechanism of spinal cord injury, 14 papers for axon regeneration, 8 papers for the function of growth cone, 8 papers for the oligodendrocytes, 7 papers for neural stem cells and the left 12 papers for neurotrophic factor. Other articles were deleted. DATA SYNTHESIS ： ①Base of functional recovery after spinal cord injury： The regeneration and elongation of damaged axons; The capacity of axons to penetrate the scar; Re-growth in the direction of appropriate target regions; Cessation of axonal growth, formation of terminal arbors and formation of synaptic contacts with target neurons; The restoration of functional neurotransmission and the recovery of function.②Neuropathological analysis of spinal cord injury： the primary and secondary damage after spinal cord injury.③Molecular biological mechanism of spinal cord injury： The growth cone is important for the establishment of neural circuitry during neural development and regeneration in the adult CNS after injury; Central nerve system myelin protein is inhibitory for axonal growth; cell membrane and intracellular signal transmission. ④The important cells and cytokine of spinal cord injury： oligodendrocyte, leukemia inhibitory factor, minocycline and endogenous neural stem cells. ⑤Animal models of spinal cord injury： The most common models are total transections, partial transections and contusions. ⑥Prospect of researches on spinal cord injury： The therapy of neurotrophic factor and neural stem cell has been transformed to clinical practice, for example, the leukaemia inhibitory factor has been applied on clinical experiment at Ⅳ phase, and the research of the induction and proliferation of endogenous stem cells has been paid much more attention. CONCLUSION： The regeneration of spinal cord after injury is becoming possible using the therapies of neurotrophic factor and neural stem cell. It would be an ideal direction in the near future to investigate the mechanisms of axon regeneration induced by neurotrophic factor intervention in the research areas of spinal cord injury. It would also play a vital role to reveal the proliferation and differentiation of endogenous neural stem cells in repairing the injury of spinal cord.