Microscale Axon Repair As A Novel Paradigm For Nerve Injuries

描述（由申请人提供）：中枢神经系统损伤会导致永久性残疾，是当今医学界尚未解决的重大挑战。除了对患者生活质量的破坏性影响外，这些伤害还给社会带来了巨大的经济负担。虽然大量的研究工作正在进行中，以促进受损神经细胞轴突的再生，功能性神经回路的重建仍然是一个遥远的目标。相比之下，很少有人关注的可能性，轴突可能是在细胞水平上的手术修复，在急性设置重建功能。当然，这种方法的障碍是，精确操纵直径仅为一微米的轴突超出了我们目前的外科技术。然而，正是在这种小的长度尺度上，微米和纳米技术才脱颖而出。在最近的工作中，我们开发了利用短程电动现象的原型微和纳米器件，以证明这种方法的原理的早期技术证明。在尤里卡基金的申请中，我们建议从生物学的角度严格检查轴突微修复，以确定这种新方法治疗神经损伤的真正潜力。我们将特别研究在两个轴突片段融合修复或拼接在一起后，轴突功能重建到什么程度。特别是，我们将解决是否传播的动作电位活动和轴突运输可以证明发生在轴突节段已重新连接彼此。与刺激损伤后轴突再生长和再生的常规方法相比，微设备辅助的轴突重建代表了范式转变。这项研究的结果可能为潜在的神经修复新方法提供生物学基础，并有助于满足紧迫的临床需求。公共卫生相关性：尤里卡申请中提出的实验研究探索了潜在的神经修复新方法的生物学基础。由于今天的医学没有提供可以在神经通路损伤后重建功能的特定疗法，因此该项目与临床需求领域直接相关。

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.