Plasticity and Regeneration in the Primate Spinal Cord

灵长类脊髓的可塑性和再生

• 批准号: 8640211
• 负责人: JACQUELINE C BRESNAHAN
• 金额: $ 111.68万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-15 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8640211
• 关键词: Aftercare; Anatomy; Animal Model; Behavioral; Brain Stem; Cell Nucleus; Cervical spinal cord structure; Chondroitinases; Chronic; Collaborations; DNA Sequence Rearrangement; Distal; Effectiveness; Electrodes; Exhibits; Flexor; Forelimb; Goals; Grant; Human; Hyaluronidase; Implanted Electrodes; Injury; Intervention; Knowledge; Locomotion; Methods; Modeling; Molecular; Monkeys; Motor Cortex; Motor Skills; Movement; Muscle; Natural regeneration; Nervous System Trauma; Primates; Property; Recovery; Recovery of Function; Reporting; Research; Rodent; Spinal Cord; Spinal cord injury; Synapses; System; Techniques; Testing; Time; Translations; Treatment Efficacy; Work; awake; efficacy testing; functional improvement; functional outcomes; nonhuman primate; novel strategies; programs; research study; working group

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.

描述(申请人提供)：这是加州大学圣迭戈分校、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的专家合作研究非人类灵长类脊髓的可塑性和再生。我们的目标是增进脊髓损伤(SCI)研究的知识和翻译相关性。鉴于过去5年在该模型中的发现，我们将重点放在更好地理解和放大灵长类系统中揭示的内源性可塑性的努力上，并测试在非灵长类模型中发现的主要潜在治疗方法的翻译。目的1：研究灵长类脊髓损伤后自发性前肢功能改善的电生理和解剖学机制。像人类一样，猴子在C7半切后表现出自发的改善(但不是完全恢复)，我们已经发现与这种功能改善相关的灵长类动物皮质脊髓投射的自发萌发程度显著。目标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)机制的时间进程。目标2和3：测试促进康复的候选疗法脊髓损伤的灵长类模型不仅对于测试在啮齿动物身上发现的疗法的有效性，而且对于开发向更大的灵长类系统提供潜在治疗的方法也是重要的。在这笔赠款的最后一期，我们已经测试了几种疗法，并计划在当前的赠款期间专注于新的、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相同的技术来检查以下各项的功能、电生理和解剖学后果：目标2：使用皮质植入电极的慢性、间歇性刺激，以驱动备用皮质脊髓投射和脊髓内回路的可塑性。目的3：脊髓损伤后的Chase治疗。