Plasticity and Regeneration in the Primate Spinal Cord

描述（由申请人提供）：这是UCSD，UCLA，UCSF，UC Irvine和UC Davis的专家之间的合作，以检查非人类灵长类动物脊髓的可塑性和再生。我们的目标是提高对脊髓损伤（SCI）研究的认识和翻译相关性。鉴于该模型过去5年的研究结果，我们将重点放在更好地理解和放大灵长类动物系统中揭示的内源性可塑性，并测试在非灵长类动物模型中发现的领先潜在治疗方法的翻译上。目的1：研究灵长类动物脊髓损伤后前肢功能自发改善的电生理和解剖机制。 像人类一样，猴子在C7半切后表现出自发性改善（但不是完全恢复），我们已经确定了与这种功能改善相关的灵长类皮质脊髓投射的显著程度的自发发芽。目的1将研究与行为改善相关的分子、电生理和系统水平（包括皮质脊髓和非皮质脊髓）机制的时间过程。目标2和3：SCI的灵长类动物模型不仅对于测试啮齿类动物中发现的治疗方法的有效性非常重要，而且对于开发向更大的灵长类动物系统提供潜在治疗方法也非常重要。我们已经测试了几种疗法在这个补助金的最后一段时间，并计划在当前的补助金期间，重点关注新的，有前途的方法，目标是增强可塑性和恢复。我们将使用与目标1中相同的技术来检查以下内容的功能、电生理和解剖学后果：目标2：使用皮质植入电极进行慢性间歇性刺激，以驱动脊髓皮质投射和椎管内回路的可塑性。目的3：SCI后追踪治疗。

DESCRIPTION (provided by applicant): This is a collaboration between experts at UCSD, UCLA, UCSF, UC Irvine, and UC Davis to examine plasticity and regeneration in the non-human primate spinal cord. Our goal is to enhance knowledge and translational relevance of research on spinal cord injury (SCI). Given findings of the last 5 years in this model, we focus this renewal on efforts to better understand and amplify the endogenous plasticity revealed in the primate system, and to test the translation of leading potential treatments discovered in non-primate models. Aim 1: Examine Electrophysiological and Anatomical Mechanisms Underlying Spontaneous Forelimb Functional Improvement After Primate SCI. Like humans, monkeys exhibit spontaneous improvement (but not full recovery) after C7 hemisection, and we have identified a remarkable degree of spontaneous sprouting of the primate corticospinal projection in association with this functional improvement. Aim 1 will examine the time course of molecular, electrophysiological and systems-level (both corticospinal and non-corticospinal) mechanisms associated with behavioral improvement. Aims 2 and 3: Test Candidate Therapies for Promoting Recovery The primate model of SCI is important not only for testing the efficacy of therapies discovered in rodents, but also for developing methods to deliver potential treatments to the larger primate system. We have tested several therapies in the last period of this grant, and plan to focus on new, promising approaches in the current grant period that target enhancement of plasticity and recovery. We will use the same techniques as in Aim 1 to examine the functional, electrophysiological, and anatomical consequences of the following: Aim 2: Chronic, Intermittent Stimulation with Cortically-Implanted Electrodes to Drive Plasticity of Spared Corticospinal Projections and Intraspinal Circuits. Aim 3: Chase Treatment after SCI.