Effects of the SCI Microenvironment on Intra-axonal Signaling

轴突在神经系统中提供长距离通信。损伤后轴突的再生 spina！脊髓带来的潜力，重新连接尾脊髓喙！脑干和大脑， 恢复感觉和运动功能。在神经领域取得了重大进展！修理 有希望恢复脊髓损伤的功能，特别是当干预措施可以结合起来， 针对多种修复机制。本项目提出的研究将探索细胞内 脊髓损伤干预改善功能恢复的潜在机制，重点是新的 轴突间室的相互作用。我们将检验受伤者的微环境 spina！旨在克服抑制性微环境的脊髓和干预措施可以调节内 轴突信号事件集中在局部蛋白质合成机制，这有助于轴突 生长和成熟。我们会的！用两个具体目标来检验这一假设， 轴突生长和轴突内信号传导方面的首席研究员，拥有项目1（Houle）的专业知识， 脊髓损伤的再生疗法和脊髓祖细胞疗法的项目II（Fischer） 损伤这个项目的第一个目的是询问已经被证明可以改善的运动/训练方案 脊髓损伤的恢复通过转录后机制调节轴突生长潜力。 将使用原代神经元培养物测试整体和轴突内的翻译控制机制 以及将周围神经移植到横断的脊髓中。第二个目标是询问是否使用前体细胞 可以直接调节轴突内信号传导以调节内在生长潜力， 通过轴突mRNA运输和翻译控制机制促进轴突成熟。我们将整合 这些数据与项目II一起解决宿主轴突与移植前体相互作用时的mRNA翻译 SCI细胞这些实验的总体目标是揭示增强的潜在机制。 轴突生长和信号传导，可用于合理地微调未来的神经修复策略。

Axons provide long-range communication in the nervous system. Regeneration of axons in the injured spina! cord brings the potential to reconnect the caudal spinal cord to rostra! brain stem and cerebrum and restore sensory and motor function. Significant advances have been made in the field of neura! repair that hold promise for restoring function in spinal cord injury, particularly when interventions can be combined to target multiple repair mechanisms. The studies proposed in this project will explore the intracellular mechanisms underlying improved functional recovery in spinal cord injury interventions, focusing on novel interactions in the axonal compartment. We will test the hypothesis that the microenvironment of the injured spina! cord and interventions aimed at overcoming the inhibitory microenvironment can modulate intra- axonal signaling events that converge on the local protein synthesis machinery and this contributes to axonal growth and maturation. We wil! test this hypothesis with two specific aims that bring together expertise of the principal investigator in axonal growth and intra-axonal signaling with expertise from Project 1 (Houle) in regenerative therapies for spinal cord injury and Project II (Fischer) in progenitor cell therapies for spinal cord injury. The first aim of this project asks if exercise/training regimens that have been shown to improve recovery from spinal cord injury regulate axonal growth potential through post-transcriptional mechanisms. Both overall and intra-axonal translational control mechanisms will be tested using primary neuronal cultures and peripheral nerve grafting into the transected spinal cord. The second aim will ask if precursor cells used for spinal cord injury can directly modulate intra-axonal signaling to regulate the intrinsic growth potential and maturation of axons through axonal mRNA transport and translational control mechanisms. We will integrate these data with Project II to address mRNA translation in host axons as they interact with grafted precursor cells in SCI. The overall objective of these experiments is to uncover mechanisms underlying enhanced axonal growth and signaling that can be used to rationally fine tune future neural repair strategies.