Neuronal Plasticity and Recovery of Function After Stroke

中风是一种毁灭性的疾病，导致神经元死亡 和神经系统残疾我们已经证明大脑形成新神经元的固有能力 连接和恢复中风后失去的功能可以通过中和抑制性质来增强 通过中和蛋白质Nogo-A的抗体治疗，我们现在计划研究 抗Nogo-A免疫疗法增强脑缺血再灌注损伤中的功能恢复和神经元可塑性的能力， 慢性脑卒中大鼠这是一个令人兴奋和新颖的研究领域，可能会使更多人受益 患有慢性神经功能障碍的患者，即使是那些由除 中风此外，了解抗Nogo-A抗体背后的可塑性相关分子的变化 在中风的慢性阶段给予免疫治疗可能会导致改善治疗方法， 未来的临床应用因此，我们假设，当给予慢性炎症患者抗Nogo-A免疫治疗时， 中风受损的老年大鼠将导致改善的功能结果，增强的解剖可塑性， 以及对感觉运动恢复很重要的大脑区域的特定基因组变化。我们将测试我们的 具体目标#1-确定是否用抗Nogo治疗- 在缺血性中风后两个月给予免疫治疗可导致行为恢复， 老鼠会我们将在老年动物中使用感觉运动恢复的行为测试并进行长期研究 结果，以提高这些结果的临床应用的翻译。具体目标#2-确定 抗Nogo-A免疫治疗是否会导致神经解剖学可塑性， 老年大鼠缺血性中风后两个月。这一目标将采用神经解剖束跟踪 和Golgi-Cox染色以检查感觉运动重要区域中的轴突和树突可塑性 复苏具体目标#3-确定对侧前肢皮质是否介导行为 在老年大鼠中风后两个月给予抗Nogo-A免疫治疗时的恢复。这一目标 将研究病灶对侧皮质和其他皮质下连接的重要性， 在中风后两个月给予抗Nogo-A治疗后改善功能结果。具体 目的#4-检查病灶同侧和对侧皮质区域的基因组变化以及相关的 中风后两个月给予抗Nogo-A免疫治疗的老年大鼠的皮质下区域。 了解抗Nogo-A免疫治疗中可塑性相关分子的变化 中风的慢性阶段可能导致未来临床使用的改进的治疗方法。

Stroke is a devastating disorder that leads to neuronal death and neurologic disability. We have shown that the brain's inherent ability to form new neuronal connections and restore lost function after stroke can be enhanced by neutralizing the inhibitory nature of the adult CNS through antibody therapy that neutralizes the protein Nogo-A. We now plan to study the ability of anti-Nogo-A immunotherapy to enhance functional recovery and neuronal plasticity in the chronic stroke impaired rat. This is an exciting and novel area of research and may benefit many more patients who suffer with chronic neurologic disabilities, even those resulting from causes other than stroke. In addition, understanding changes in plasticity-related molecules underlying anti-Nogo-A immunotherapy given at a chronic stage of stroke could lead to improved therapeutic approaches for future clinical use. Therefore, we hypothesize that anti-Nogo-A immunotherapy when given to chronic stroke-impaired aged rats will result in improved functional outcome, enhanced anatomical plasticity, and specific genomic changes in brain regions important for sensorimotor recovery. We will test our hypothesis in the following specific aims: Specific Aim #1- Determine whether treatment with anti-Nogo- A immunotherapy results in behavioral recovery when given two months after ischemic stroke in the aged rat. We will use behavioral tests of sensorimotor recovery in the aged animal and study long term outcomes in order to enhance the translation of these results to clinical use. Specific Aim #2- Determine whether treatment with anti-Nogo-A immunotherapy results in neuroanatomical plasticity when given two months after ischemic stroke in the aged rat. This aim will employ neuroanatomical tract tracing and Golgi-Cox staining to examine axonal and dendritic plasticity in areas important for sensorimotor recovery. Specific Aim #3- Determine whether the contralesional forelimb cortex mediates behavioral recovery when anti-Nogo-A immunotherapy is given two months after stroke in the aged rat. This aim will investigate the importance of the contralesional cortex and other subcortical connections in improving functional outcome after anti-Nogo-A therapy when given at two months after stroke. Specific Aim #4- Examine genomic changes in ipsilesional and contralesional cortical regions and pertinent subcortical areas in aged rats given anti-Nogo-A immunotherapy two months after stroke. Understanding changes in plasticity-related molecules underlying anti-Nogo-A immunotherapy given at a chronic stage of stroke could lead to improved therapeutic approaches for future clinical use.