Neuronal Plasticity and Recovery of Function After Stroke

中风是一种会导致神经元死亡的破坏性疾病。 和神经性残疾。我们已经证明了大脑形成新神经元的固有能力 通过中和抑制的性质，可以增强中风后失去的联系和恢复功能 通过中和Nogo-A蛋白的抗体治疗成人中枢神经系统。我们现在计划研究 抗Nogo-A免疫治疗对大鼠神经功能恢复和神经元可塑性的影响 慢性卒中损伤大鼠。这是一个令人兴奋和新颖的研究领域，可能会使更多的人受益 患有慢性神经功能障碍的患者，即使是由其他原因引起的 卒中。此外，了解抗Nogo-A基因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，我们假设当给予抗Nogo-A免疫疗法时，慢性 卒中损伤的老年大鼠将导致功能结果的改善，解剖可塑性增强， 以及对感觉运动恢复至关重要的大脑区域的特定基因组变化。我们将测试我们的 以下具体目标中的假设：具体目标1--确定是否使用抗NOGO治疗-- 缺血性卒中后两个月给予免疫治疗可导致行为恢复 年迈的老鼠。我们将使用老年动物感觉运动恢复的行为学测试，并进行长期研究 结果，以加强将这些结果转化为临床应用。具体目标2--确定 抗Nogo-A免疫治疗在给予时是否会导致神经解剖可塑性 老年大鼠缺血性卒中后2个月。这个目标将使用神经解剖学的轨迹追踪。 高尔基-考克斯染色检查感觉运动重要区域的轴突和树突的可塑性 恢复。具体目标#3-确定对侧前肢皮质是否调节行为 老年大鼠卒中后两个月给予抗Nogo-A免疫治疗后恢复。这一目标 将研究对侧皮质和其他皮质下连接在脑内的重要性 卒中后两个月给予抗Nogo-A治疗可改善功能结果。特定的 目的#4-检查患侧和对侧皮质区域的基因组变化和相关 卒中后两个月给予抗Nogo-A免疫治疗的老年大鼠皮质下区域。 了解参与抗Nogo-A免疫治疗的可塑性相关分子的变化 中风的慢性期可能会为未来的临床使用带来改进的治疗方法。

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.