Neuron Plasticity and Recovery of Function After Stroke

描述：（申请人摘要中的逐字记录）中风是一种毁灭性的疾病， 导致神经元死亡和功能丧失的临床问题。 有趣的是，在围产期类似的脑损伤往往会导致 更好的功能结果。这种改善的恢复被认为是由于 年轻大脑固有的“可塑性”，随着新的 神经解剖学连接从备用神经组织取代受损 途径。本提案的主要目标是促进神经解剖学 可塑性成人脑损伤后，从而提高功能 结果。我们最近发现一种诱导成年人 可塑性是通过阻断髓鞘相关的神经突抑制蛋白 诺戈A我们现在计划使用临床相关的局灶性缺血性卒中模型 以确定Nogo-A阻断是否导致神经解剖学可塑性， 功能恢复和假设：局灶性脑缺血后 损伤，髓鞘相关神经突抑制蛋白Nogo-A的阻断 与单克隆抗体IN-1的结合将导致皮质传出可塑性 和改善的功能结果。 将在以下具体目标中检验这一假设： 具体目标#1将确定中风后Nogo-A的阻断是否导致 未切除皮质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将确定中风后Nogo-A的阻断是否导致 使用中风影响的前肢表现的行为恢复 对前肢运动和感觉功能的特殊测试。 具体目标#3将确定改善前肢使用的恢复是否直接 与新的结构可塑性从备用皮质使用 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返回 对患有缺血性以及其他原因的患者失去功能 通过增强大脑的固有能力来使用未受损的脑损伤 组织修复和恢复。

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.