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

这一建议旨在扩大轴突发芽的研究 由神经生长因子（ANTI-NGF）抗体诱导。 数据 实验室收集的数据表明， 感觉神经元的突起在手术去神经后发芽。 每日给予神经生长因子（NGF） 促进发芽。 相反，每天给予抗- 神经生长因子增加了50%的感觉轴突发芽手术 失神经和未受伤的哺乳动物。 当前的目标 项目是通过检查脊柱白色来扩展这项工作 物质和背角，突触的网站之一， 感觉神经元 在拨款的第一年，轴突 Lissauer氏束的数目。 的具体目标 建议的项目是1）量化轴突数量的影响 在背柱中，并确定感觉和 和2）量化对突触的影响 给予抗-NGF的未受伤哺乳动物的背角中的数量。 这些方法将是超微结构定量的， 脊髓白色物质的有髓和无髓轴突， 体视学技术应用于超微结构水平， 背角突触的数量 鉴于椎管内发芽可能与功能性 恢复和操纵内源性神经生长因子的水平， 增强脊柱内发芽，这些研究可能会导致 临床上适用的操作。

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.