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Clarification and control of the mechanism of motor and sensory nerve regeneration after transection

横断后运动和感觉神经再生机制的阐明和控制

基本信息

批准号：
08407050
负责人：
OCHI Mitsuo
金额：
$ 11.46万
依托单位：
Shimane Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1999
项目状态：
已结题

项目摘要

1.To determine the effects of the conditioning lesion on the peripheral nerve regeneration, we measured the axonal outgrowths of sensory neurons in response to peripheral nerve injuries using an in vitro tissue culture system of dorsal root ganglia (DRG) with attached nerve stump. It was concluded that the conditioning effect was not merely restricted to the ipsilateral neurons but also affected undamaged sensory neurons of the contralateral DRG. Furthermore we studied if the conditioning effect affected the nerve regeneration in the contralateral nerves in vivo. In results, the initial delay of regeneration was shorter and the expression of IL-1b and TGF-b1 in the contralateral DRG was higher when the contralateral nerves were previously injured.2.To elucidate the difference in nerve regeneration between sensory neurons and motoneurons, we observed the expression of GAP-43 after transection of the sciatic nerves and confirmed the increased level of GAP-43 in anterior horn (AH) cells f … More ollowed that in DRG cells. In addition, we studied the detail of the initial stage of nerve regeneration. After transected and sutured, the sciatic nerves were retransected at the positive pinch site and exposed the proximal stumps to Fluoro-Gold (F-G). The F-G positive labeling was observed more dominantly in DRG cells than the spinal AH cells. These findings suggested that the regeneration of sensory neurons occurred and started earlier than that of motoneurons.3.The influence of distal nerve segment volume on nerve regeneration in silicon tubes, mass of nerve fragment was examined. The results indicated that the degree of nerve regeneration does not correlate with the volume of distal nerve segment. We also examined whether giving monoclonal antibodies (MoAb) to intercellular adhesion molecule(ICAM-1) and leukocyte function associated antigen (LFA-1) can improve nerve regeneration in allogeneic mice. We conclude that giving MoAb could effectively improve nerve regeneration in grafted allogeneic nerve segments.4.To date, the expression of cytokines in the neurons in the entrapment neuropathy still remains unclear. We observed the changes of IL-1 and TGF-b1 in the DRG cells during both formation and recovery process, together with electrophysiological changes. After expression of IL-1 reached its peak, expression on TGF-b1 peaked and thereafter changes of motor nerve conduction velocity followed the changes of cytokines in the formation as well as the recovery process. In conclusion, cytokines are deeply involved in the formation as well as the recovery process of entrapment neuropathy. Less

1.采用背根神经节（DRG）体外组织培养技术，观察周围神经损伤后感觉神经元轴突的生长情况，探讨条件性损伤对周围神经再生的影响。结果表明，条件反射的作用不仅限于同侧神经元，而且也影响对侧背根神经节未受损的感觉神经元。此外，我们还研究了在体条件作用是否影响对侧神经的再生。结果表明，对侧背根神经损伤后，再生延迟时间较短，且对侧背根神经节中IL-1b和TGF-β 1的表达较高。2.为了阐明感觉神经元和运动神经元在神经再生方面的差异，我们观察了坐骨神经切断后GAP-43的表达，并证实了GAP-43在前角（AH）细胞中的表达水平增加， ...更多信息在背根神经节细胞中也是如此。此外，我们还研究了神经再生初期的细节。切断并缝合后，在正夹点处再次切断坐骨神经，并将近端残端暴露于Fluoro-Gold（F-G）。F-G阳性标记主要见于DRG细胞，而脊髓AH细胞则较少见。实验结果表明，感觉神经元的再生早于运动神经元。3.在硅胶管、神经碎片质量中，观察神经远端节段体积对神经再生的影响。结果表明，神经再生的程度与远端神经节段的体积无关。我们还研究了给予细胞间粘附分子（ICAM-1）和白细胞功能相关抗原（LFA-1）的单克隆抗体（MoAb）是否能促进同种异体小鼠的神经再生。结论：给予单克隆抗体能有效促进同种异体神经移植段的神经再生。4.迄今为止，卡压性神经病神经元中细胞因子的表达尚不清楚。我们观察了DRG细胞在形成和恢复过程中IL-1和TGF-β 1的变化以及电生理变化。在IL-1表达达到高峰后，TGF-β 1表达达到高峰，运动神经传导速度的变化与细胞因子的变化相一致。总之，细胞因子在嵌压性神经病的形成和恢复过程中起重要作用。少