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Microscale Axon Repair As A Novel Paradigm For Nerve Injuries

微型轴突修复作为神经损伤的新范例

基本信息

批准号：
8094388
负责人：
DAVID W SRETAVAN
金额：
$ 30.28万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-07-15 至 2012-12-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Injuries to the central nervous system result in permanent disability and represent a major unmet challenge in medicine today. In addition to the devastating impact on patient quality of life, these injuries impose a large economic burden on society. Although substantial research efforts are underway to promote the regeneration of injured nerve cell axons, the re-establishment of functional neural circuits remains a distant goal. In contrast, little attention has been paid to the possibility that axons may be surgically repaired at the cellular level in the acute setting to reconstitute function. The barrier to this approach is of course the fact that the precise manipulation of axons as small as one micron in diameter is beyond our current surgical technology. However, it is precisely at this small length scale that micro and nanotechnology excel. In recent work, we developed prototype micro and nanodevices that utilize short-range electrokinetic phenomenon to demonstrate early technical proof of principle for this approach. In this application for EUREKA funding, we propose to critically examine axon micro-repair from a biological perspective in order to determine the true potential of this novel methodology for nerve injury treatment. We will specifically investigate to what degree axonal function is reconstituted after the fusion repair or splicing together of two axon segments. In particular we will address whether the propagation of action potential activity and axonal transport can be demonstrated to occur in axon segments that have been reconnected with one another. Microdevice-assisted reconstruction of axons represents a paradigm shift compared to conventional approaches of stimulating axon re-growth and regeneration after injury. The results from this study may provide the biological underpinnings to a potentially new method of nerve repair and help meet an urgent clinical need. PUBLIC HEALTH RELEVANCE: The experimental studies proposed in this EUREKA application explore the biological underpinnings for a potentially new method of nerve repair. Since medicine today offers no specific therapy that can reconstitute function after injuries to neural pathways, this project has direct relevance to an area of clinical need.

描述（由申请人提供）：中枢神经系统损伤导致永久性残疾，是当今医学中尚未解决的主要挑战。除了对患者的生活质量造成毁灭性影响外，这些伤害还给社会带来了巨大的经济负担。尽管大量的研究工作正在进行中，以促进损伤的神经细胞轴突的再生，功能神经回路的重建仍然是一个遥远的目标。相比之下，很少有人注意到轴突在急性情况下可以在细胞水平上通过手术修复以重建功能的可能性。当然，这种方法的障碍在于精确操纵直径为一微米的轴突超出了我们目前的外科技术。然而，正是在这种小长度尺度上，微型和纳米技术表现出色。在最近的工作中，我们开发了微型和纳米器件原型，利用短程电动现象来证明这种方法的早期技术原理。在EUREKA资助的这项申请中，我们建议从生物学角度严格检查轴突微修复，以确定这种新方法在神经损伤治疗中的真正潜力。我们将具体研究两个轴突片段的融合修复或拼接后轴突功能的重建程度。特别是，我们将讨论动作电位活动的传播和轴突运输是否可以证明发生在彼此重新连接的轴突段中。与刺激损伤后轴突再生的传统方法相比，微设备辅助轴突重建代表了一种范式转变。这项研究的结果可能为神经修复的潜在新方法提供生物学基础，并有助于满足迫切的临床需求。公共卫生相关性：本EUREKA应用程序中提出的实验研究探索了神经修复新方法的生物学基础。由于今天的医学没有提供能够在神经通路损伤后重建功能的特定治疗，因此该项目与临床需求领域直接相关。