Neuron Plasticity and Recovery of Function After Stroke

描述：(逐字摘自申请者的摘要)中风是一种毁灭性的打击 导致神经元死亡和功能丧失的临床问题。 有趣的是，围产期类似的脑损伤通常会导致 更好的功能结果。这种改善的复苏被认为是由于 年轻大脑与生俱来的“可塑性”，随着新的 备用神经组织替代受损神经组织的神经解剖连接 小路。本提案的主要目标是促进神经解剖学 成人脑损伤后的可塑性，从而改善功能 结果。我们最近展示了一种强大的技术来诱导成人 可塑性是通过阻断髓鞘相关的轴突抑制蛋白来实现的 NOGO-A我们现在计划使用一种临床相关的局灶性缺血性中风模型 为了确定阻断Nogo-A是否会导致神经解剖可塑性和 功能恢复和假设：局灶性脑缺血后 髓鞘相关神经突起抑制蛋白Nogo-A的损伤和阻断 使用单抗IN-1将导致皮质传出可塑性 从保留的、未损伤的皮质中分离出来，并改善功能结果。 这一假设将在以下具体目标中得到检验： 具体目标1将确定卒中后阻断Nogo-A是否会导致 未消融的备用皮质中分离皮质纤维的结构可塑性 使用神经解剖追踪技术。 具体目标#2将确定卒中后阻断Nogo-A是否会导致 中风对前肢功能的行为恢复的影响 前肢运动和感觉功能的特殊测试。 具体目标#3将确定在前肢使用中提高恢复是否直接 与来自备用皮质的新结构可塑性有关 电生理学方法来定义新的神经元通路。 这些研究的结果可能会导致新的治疗方法 缺血性脑缺血患者的功能丧失以及其他原因 通过增强大脑使用未受损的固有能力而造成的脑损伤 用于修复和恢复的组织。

DESCRIPTION: (Verbatim from the Applicant's Abstract) Stroke is a devastating clinical problem which leads to neuronal death and functional loss. Interestingly, similar brain damage in the perinatal period often results in better functional outcome. This improved recovery is thought to be due to the inherent "plasticity" of the young brain, with the formation of new neuroanatomical connections from spared neural tissue replacing damaged pathways. The main goal of the present proposal is to promote neuroanatomical plasticity following adult brain damage, and thereby improve functional outcome. We have recently shown that a powerful technique to induce adult plasticity is by blockade of the myelin associated neurite inhibitory protein Nogo-A. We now plan to use a clinically relevant model of focal ischemic stroke to determine if Nogo-A blockade results in neuroanatomical plasticity and functional recovery and Hypothesize that: following focal ischemic brain damage, blockade of the myelin associated neurite inhibitory protein Nogo-A with the monoclonal antibody IN-1 will result in cortico-efferent plasticity from the spared, unlesioned cortex and improved functional outcome. This hypothesis will be tested in the following Specific Aims: Specific aim #1 will determine if blockade of Nogo-A following stroke leads to structural plasticity of corticofugal fibers from the spared, unablated cortex using neuroanatomical tracing techniques. Specific aim #2 will determine if blockade of Nogo-A following stroke leads to behavioral recovery in forelimb performance affected by the stroke using specific tests for forelimb motor and sensory function. Specific aim #3 will determine if improved recovery in forelimb use is directly related to the new structural plasticity from the spared cortex using electrophysiological methods to define the new neuronal pathways. The results of these studies may lead to new therapeutic approaches to return lost functions to patients suffering from ischemic as well as other causes of brain damage by enhancing the inherent ability of the brain to use undamaged tissue to repair and recover.