Microscale Axon Repair As A Novel Paradigm For Nerve Injuries

描述(由申请人提供)：中枢神经系统损伤导致永久性残疾，是当今医学中一个重大的未解决的挑战。这些伤害除了对患者的生活质量造成毁灭性的影响外，还给社会带来了巨大的经济负担。尽管促进受损神经细胞轴突再生的大量研究工作正在进行中，但重建功能神经回路仍然是一个遥远的目标。相反，很少有人注意到，在急性发作时，轴突可能会在细胞水平上进行手术修复，以重建功能。这种方法的障碍当然是这样一个事实，即对直径小至一微米的轴突的精确操作超出了我们目前的外科技术范围。然而，正是在这种小的长度尺度上，微米和纳米技术出类拔萃。在最近的工作中，我们开发了利用短程电动现象的微米和纳米原型设备，以证明这种方法原理的早期技术证明。在这次尤里卡基金的申请中，我们建议从生物学角度批判性地检查轴突微修复，以确定这一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段融合修复或拼接后轴突功能重建的程度。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被证明发生在彼此重新连接的轴突节段。与传统的刺激损伤后轴突再生长和再生的方法相比，微设备辅助的轴突重建代表着一种范式的转变。这项研究的结果可能为一种潜在的神经修复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：在这项尤里卡申请中提出的实验研究探索了一种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特定的治疗方法来恢复神经通路损伤后的功能，这个项目与临床需要的一个领域直接相关。

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.