Plasticity and Regeneration in the Primate Spinal Cord

描述（由申请人提供）：这是加州大学圣地亚哥分校、加州大学洛杉矶分校、加州大学旧金山分校、加州大学欧文分校和加州大学戴维斯分校专家之间的合作，旨在研究非人灵长类动物脊髓的可塑性和再生。我们的目标是提高脊髓损伤（SCI）研究的知识和翻译相关性。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扩大灵长类系统中揭示的内源性可塑性上，并测试在非灵长类模型中发现的领先潜在治疗方法的翻译。目的1：研究灵长类动物脊髓损伤后自发性前肢功能改善的电生理和解剖学机制。与人类一样，猴子在C7半球切除后表现出自发的改善（但不是完全恢复），我们已经发现灵长类动物皮质脊髓投影的自发发芽程度显著与这种功能改善有关。目的1将研究与行为改善相关的分子、电生理和系统水平（皮质脊髓和非皮质脊髓）机制的时间过程。目的2和3：测试促进恢复的候选疗法灵长类动物模型不仅对测试在啮齿动物中发现的治疗方法的有效性很重要，而且对于开发将潜在治疗方法应用于更大的灵长类动物系统也很重要。在本次资助的最后阶段，我们已经测试了几种治疗方法，并计划在当前的资助阶段专注于新的、有希望的方法，以增强可塑性和恢复为目标。我们将使用与目标1中相同的技术来检查以下功能，电生理和解剖学结果：目标2：使用皮质植入电极进行慢性，间歇性刺激以驱动备用皮质脊髓投射和椎内回路的可塑性。目标3：脊髓损伤后的后续治疗。

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.