Neuronal Plasticity and Recovery of Function After Stroke

中风后神经元可塑性和功能恢复

• 批准号: 7760207
• 负责人: GWENDOLYN LOUISE KARTJE
• 金额: $ 3.4万
• 依托单位: LOYOLA UNIVERSITY CHICAGO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-15 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7760207
• 关键词: Acute; Adult; Affect; Age; Animal Welfare; Animals; Antibodies; Antibody Therapy; Area; Astrocytes; Attention; Axon; Behavioral; Bibliography; Brain; Brain Injuries; Brain region; Catheters; Cervical spinal cord structure; Cessation of life; Clinical; Clinical Trials; Clinical Trials Design; Control Animal; Corpus striatum structure; Country; Data; Disease; Environment; Environmental Impact; Equipment; Europe; Forelimb; Funding; Genomics; Golgi Apparatus; Grant; Hindlimb; Human; IACUC; Immunohistochemistry; Immunotherapy; Infusion procedures; Injection of therapeutic agent; International; Investigation; Ischemic Stroke; Knockout Mice; Laboratories; Lateral; Lead; Length; Lesion; Location; Maintenance; Maps; Mediating; Methods; Modeling; Motor Cortex; Movement; Nature; Neurologic; Neuronal Plasticity; Neurons; Nogo protein; Oligodendroglia; Outcome; Pathway interactions; Patients; Phase I Clinical Trials; Principal Investigator; Progress Reports; Proteins; Publications; Rattus; Recovery; Recovery of Function; Red nucleus structure; Relative (related person); Reporting; Research; Research Ethics Committees; Resources; Sensorimotor functions; Side; Site; Spinal cord injury; Staging; Staining method; Stains; Stroke; Stroke Volume; Structure; Switzerland; Testing; Thalamic structure; Therapeutic; Therapeutic Intervention; Time; Tissues; Tracer; Translating; Translations; United States National Institutes of Health; Vertebrates; Walking; abstracting; aged; aging brain; biotinylated dextran amine; clinical application; design; disability; experience; expiration; functional restoration; growth inhibitory proteins; human RTN4 protein; human subject; improved; insight; microstimulation; nerve supply; neuron loss; novel; novel therapeutic intervention; post stroke; professor; programs; protein expression; repaired; research study; stroke recovery; stroke therapy; treatment duration

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.

中风是一种破坏性的疾病，会导致神经元死亡 和神经功能障碍。我们已经证明大脑具有形成新神经元的固有能力 通过中和抑制性质可以增强中风后的连接并恢复失去的功能 通过抗体疗法中和 Nogo-A 蛋白，对成人中枢神经系统产生影响。我们现在计划学习 抗Nogo-A免疫疗法增强功能恢复和神经元可塑性的能力 慢性中风受损大鼠。这是一个令人兴奋且新颖的研究领域，可能会使更多人受益 患有慢性神经功能障碍的患者，即使是由其他原因造成的患者 中风。此外，了解抗 Nogo-A 的可塑性相关分子的变化 在中风慢性阶段给予免疫疗法可能会改善中风的治疗方法 未来的临床使用。因此，我们假设，当给予慢性病患者时，抗Nogo-A免疫疗法 中风受损的老年大鼠将改善功能结果，增强解剖可塑性， 以及对感觉运动恢复重要的大脑区域的特定基因组变化。我们将测试我们的 假设在以下具体目标中：具体目标#1-确定是否使用抗Nogo治疗- 在缺血性中风后两个月进行免疫疗法可导致行为恢复 老老鼠。我们将使用老年动物感觉运动恢复的行为测试并进行长期研究 成果，以加强这些结果到临床应用的转化。具体目标#2——确定 抗Nogo-A免疫疗法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。该目标将采用神经解剖学路径追踪 和高尔基-考克斯染色来检查对感觉运动重要的区域的轴突和树突可塑性 恢复。具体目标#3-确定对侧前肢皮层是否介导行为 老年大鼠中风后两个月给予抗 Nogo-A 免疫疗法即可恢复。这个目标 将研究对侧皮质和其他皮质下连接的重要性 中风后两个月给予抗 Nogo-A 治疗可改善功能结果。具体的 目标#4-检查同侧和对侧皮质区域以及相关的基因组变化 中风两个月后接受抗 Nogo-A 免疫治疗的老年大鼠的皮层下区域。 了解抗 Nogo-A 免疫疗法的可塑性相关分子的变化 中风的慢性阶段可能会导致未来临床使用的治疗方法得到改进。