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REGROWTH OF SPINAL CORD AXONS FOLLOWING COLD INJURY

冷损伤后脊髓轴突的再生

基本信息

批准号：
3407735
负责人：
GEORGE H. COLLINS
金额：
$ 12.86万
依托单位：
UPSTATE MEDICAL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1987
资助国家：
美国
起止时间：
1987-07-01 至 1991-06-30
项目状态：
已结题

项目摘要

Utilizing a newly developed model which produces a freezing injury in rat spinal cords, the reparative and regenerative response of the tissue will be studied. The regrowth of axons in this experimental model provides opportunities to extend our understanding of the regenerative potential of mammalian central nervous tissue following traumatic or other injury. In these experiments we are specifically interested in three areas. In the first, we will develop more information about the current model, particularly in terms of the nature and source of the cellular matrix, the relationship of growing axons to the matrix, the breakdown of tissue in the Wallerian zone and the relationships of growing axons in the Wallerian zone. We will perform these studies, at first, upon the experimental form which is characterized by optimal development of the cellular matrix and axonal regrowth. This lesion will be identified in our initial experiments. Subsequently we plan to explore those lesions which represent identifiable variations from the optimal so as to examine more thoroughly the influence of axons, various glial elements, Schwann cells and mesenchymal components upon the regrowth of axons into the injury zone. Evaluation of these potential changes will be by electron microscopy and immunohistochemistry. Secondly, we will perform experiments which will verify the observation, made by light microscopy, that axons regrow into the lesion. These studies will be performed on the optimal model and on another model in which all the adjacent roots will be cut prior to freezing the cord. Analysis of the effects of these studies will be through the use of tracer techniques. Somatosensory evoked potentials will also be employed to permit in vivo evaluation of the status of axons within the lesion. Long range studies up to 18 months will determine whether axons can spontaneously regrow through the Wallerian zone following phagocytic clean-up of the area. And finally, we plan to investigate the following phagocytic clean-up of the area. We will study the vascular response to the lesion by measuring the permeability of intravenous horseradish peroxidase through the vessel walls. By light and electron microscopy the morphologic changes occurring in glia, axons, myelin, pial and subpial tissues will be evaluated. By immunohistochemistry we will attempt to identify other changes that may occur in the cellular and extra-cellular matrix.

利用一种新开发的模型，大鼠脊髓损伤的修复和再生将研究组织的反应。轴突的再生这个实验模型提供了机会，了解哺乳动物中枢神经系统的再生潜力神经组织创伤或其他损伤。在这些我们对三个方面的实验特别感兴趣。在第一，我们会对现有的模型进行更多的信息，特别是在细胞的性质和来源方面，基质，生长轴突与基质的关系，华勒区组织的破坏以及在沃勒区生长轴突我们将执行这些研究，首先，在实验的形式，这是其特征在于细胞基质的最佳发育，轴突再生这个病变将在我们最初的实验随后我们计划探查那些病变，表示与最优值的可识别变化，更彻底地检查轴突，各种神经胶质细胞，元件，雪旺细胞和间充质成分，轴突再生长到损伤区。评价这些潜在的变化将通过电子显微镜和免疫组化其次，我们将进行实验这将验证光学显微镜的观察结果，轴突在损伤处再生。这些研究将在最优模型和另一个模型，其中所有相邻的在冷冻脐带之前将切断根部。分析这些研究的效果将通过使用示踪剂技术. 体感诱发电位也将是用于允许轴突状态的体内评价在病变内。长达18个月的长期研究将确定轴突是否可以通过吞噬细胞清理该区域后的沃勒区。和最后，我们计划研究以下吞噬清除的区域。我们将研究血管对病变的反应，测定静脉辣根过氧化物酶的渗透性穿过血管壁通过光学和电子显微镜，神经胶质、轴突、髓鞘、软脑膜和评价软膜下组织。通过免疫组织化学，将尝试识别可能发生在细胞外基质。