NERVE GROWTH FACTOR--AXONAL AND SYNAPTIC CHANGES IN THE SPINAL CORD

这项建议旨在扩大对轴突萌发的研究。 由抗神经生长因子抗体(抗NGF)诱导。数据 在这个实验室收集的数据表明，中央 感觉神经元的突起在手术去神经后萌发。 每日服用神经生长因子(NGF)没有 促进发芽。反之，每日服用抗- 神经生长因子在外科手术中增加50%的感觉轴突出芽 丧失神经和未受伤的哺乳动物。当前的目标是 项目是通过检查脊髓白质来扩展这项工作 物质和背角，突触部位之一 感觉神经元。在拨款的第一年，轴突 Lissauer氏束内的数量。《公约》的具体目标 建议的项目是1)量化对轴突数量的影响 在背侧柱中，并确定感觉和 脊髓固有纤维和2)量化对突触的影响 在给予NGF抗体的情况下，未受伤的哺乳动物的后角中的数目。 该方法将对超微结构进行定量。 脊髓白质有髓轴突和无髓轴突 体视学技术在超微结构水平上的应用 背角突触的定量。 鉴于椎管内发芽可能与功能性 恢复以及内源性NGF水平的操纵可能 增强椎管内萌发，这些研究可能导致 临床上适用的手法。

This proposal is designed to extend studies of axonal sprouting induced by antibodies to Nerve Growth Factor (ANTI-NGF). Data collected in this laboratory demonstrate that the central processes of sensory neurons sprout after surgical denervation. Daily administration of Nerve Growth Factor (NGF) did not enhance the sprouting. Conversely, daily administration of ANTI- NGF increased the sensory axon sprouting by 50% in surgically denervated and uninjured mammals. The objectives of the current projects are to extend this work by examining the spinal white matter and the dorsal horn, one of the synaptic sites of the sensory neurons. During the first year of the grant, the axonal number in Lissauer's tract were determined. Specific aims of the proposed project are 1) to quantify the effects on axonal numbers in the dorsal columns and determine the proportion of sensory and propriospinal fibers and 2) to quantify the effects on synaptic number in the dorsal horn of uninjured mammals given ANTI-NGF. The methods will be ultrastructural quantitation of the myelinated and unmyelinated axons of the spinal white matter and stereological techniques applied at the ultrastructural level for the quantitation of synapses in the dorsal horn. Given the intraspinal sprouting may be related to functional recovery and that manipulating levels of endogenous NGF may enhance intraspinal sprouting, these studies may lead to manipulations that are clinically applicable.