ENHANCED REGENERATION OF NERVE AXONS BY BIOPOLYMERS

生物聚合物增强神经轴突再生

• 批准号: 2204026
• 负责人: GEORGE Davis BITTNER
• 金额: $ 6.85万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-04-01 至 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2204026
• 关键词: axon; axoplasm; denervation; electron microscopy; ethylene glycols; gel; laboratory rat; nervous system regeneration; polymers; sciatic nerve

The slow rate, incomplete extent, and poor specificity of axonal regeneration is an important medical problem associated with significant dysfunction and loss of productivity. Our long term goal is to develop techniques using polymers to improve the rate, extent, and/or specificity of nerve axon regeneration in humans. To begin at attain this goal, in this application we propose to use a biopolymer hydrogel which we have recently developed as substitute for microsuture to hold together the stumps of severed nerved bundles (Specific Aim I). We expect that this hydrogel will produce greater regenerative success than microsuture in vivo because the hydrogel causes less tissue damage. We also propose to use a biopolymer (polyethylene glycol) in hypotonic salines with reduced calcium to fuse (reconnect) the severed halves of crushed nerve axons within minutes in vitro (Specific Aim II). Finally, we propose to use our recently developed biopolymer hydrogel to add mechanical strength to axons reconnected by polyethylene glycol in vivo (Specific Aim III). This biopolymer-based technique would increase the rate (and perhaps the extent) of reconnection of severed axons with denervated tissues. We will assess the ability of these biopolymer to improve the rate, extent, and specificity of regeneration of rat sciatic axons according to morphological criteria (axolemma and axoplasmic continuity in electron micrographs, diffusion of tracers). electrophysiological criteria (conductio of action potentials), and behavioral criteria (sciatic functional index). Given that traumatic injuries to nerve axons are rather common and axonal integrity is essential for proper neuronal function , successful development of one or more of these proposed techniques using biopolymer to improve axonal regeneration would have significant medical implications for humans.

轴突的速度慢、程度不全和特异性差 再生是一个重要的医学问题，与 功能障碍和生产力下降。我们的长远目标是发展 使用聚合物来提高速度、程度和/或特异性的技术 人类神经轴突再生的研究。要从实现这一目标开始，在 在这一应用中，我们建议使用我们已有的生物聚合物水凝胶 作为微缝合的替代品，新近发展起来 被切断的神经束的树桩(特定目标I)。我们预计这一次 水凝胶将产生比微缝合更大的再生成功 活体，因为水凝胶对组织的损伤较小。我们还建议 在低渗盐水中使用生物聚合物(聚乙二醇) 用钙来融合(重新连接)被压碎的神经轴突的一半 在体外数分钟内(特异靶II)。最后，我们建议使用 我们最近开发的生物聚合物水凝胶可以增加机械强度 聚乙二醇体内重联轴突(特指目标III)。 这种基于生物聚合物的技术将提高这一速度(也许 切断的轴突与失神经组织重新连接的程度)。我们 将评估这些生物聚合物提高速度、程度、 大鼠坐骨神经轴突再生的特异性 形态标准(电子轴膜和轴浆连续性 显微照相、示踪剂的扩散)。电生理学标准 (动作电位传导)和行为准则(坐骨神经 功能指数)。 鉴于神经轴突的创伤性损伤相当常见和轴突 完整性对于正常的神经元功能至关重要，成功 使用生物聚合物开发一种或多种这些建议的技术 改善轴突再生将具有重大的医学意义 对人类的影响。