Cognitive Recovery and Neuronal Plasticity after Stroke in the Aged

老年人中风后的认知恢复和神经元可塑性

• 批准号: 7580934
• 负责人: Rebecca Lynn Gillani
• 金额: $ 3.36万
• 依托单位: LOYOLA UNIVERSITY CHICAGO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-22 至 2011-06-21
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7580934
• 关键词: Address; Area; Attenuated; Brain; Clinical; Clinical Trials; Elderly; Europe; Golgi Apparatus; Hippocampus (Brain); Human; Immunotherapy; Impaired cognition; Laboratories; Lead; Learning; Memory; Memory impairment; Modeling; Morphology; Neuronal Plasticity; Neurons; Phase I Clinical Trials; Population; Process; Purpose; Pyramidal Cells; Quality of life; Recovery; Recovery of Function; Rodent; Role; Short-Term Memory; Spinal cord injury; Stroke; Structure; Testing; Therapeutic Intervention; Translating; United States; Vertebral column; aged; cognitive recovery; density; disability; entorhinal cortex; granule cell; human RTN4 protein; improved; morris water maze; novel; repaired; research study; stellate cell; therapy development

DESCRIPTION (provided by applicant): Stroke is a major cause of disability including memory impairment. Our laboratory has shown that a novel treatment, anti-Nogo-A immunotherapy results in sensorimotor functional recovery after stroke in rodents. However, the role of anti-Nogo-A immunotherapy in memory recovery after stroke has not, as of yet, been investigated. The purpose of this proposal is to investigate anti-Nogo-A immunotherapy as a therapeutic intervention to improve memory impairment after stroke in aged rodents. Aim 1 will employ the Morris water maze to determine whether anti-Nogo-A immunotherapy after stroke in the aged attenuates memory impairment. The Morris water maze will be used to evaluate spatial reference and working memory. Aim 2 will employ Golgi-Cox analysis to determine whether anti-Nogo-A immunotherapy after stroke induces dendritic plasticity in the hippocampus and entorhinal cortex, two brain structures involved in learning and memory. Neurons in the hippocampus (CA1 pyramidal cells, CAS pyramidal cells, and DG granule cells) and entorhinal cortex (layer II stellate cells, layer III pyramidal cells, and layer V pyramidal cells) of Golgi-Cox processed brains will be examined for structural neuronal plasticity by quantification of dendritic arborization, spine density, and spine morphology. These experiments are relevant to clinical practice by addressing the significant decrease in quality of life caused by memory impairment after stroke. In addition, the translational relevance of these experiments is maximized by modeling the elderly human population, in which stroke is most prevalent, with aged rodents. Furthermore, anti-Nogo-A immunotherapy is a promising therapeutic intervention that may be quickly translated into a clinical trial for stroke. This is evidenced by the Phase 1 clinical trial that has begun in Europe to test anti-Nogo-A as a therapeutic intervention for spinal cord injury. Stroke is a major cause of disability in the United States and in many cases the disability is contributed to by cognitive impairments including memory impairments. This proposal will contribute to the development of treatments for cognitive impairments including memory impairments after stroke. In addition, this proposal will lead to important information regarding the role of neuronal plasticity in brain repair after stroke.

描述（由申请人提供）：中风是造成残疾的主要原因，包括记忆障碍。我们的实验室表明，一种新型的抗Nogo-A免疫疗法会导致啮齿动物中风后感觉运动功能恢复。然而，尚未研究抗Nogo-A免疫疗法在中风后记忆恢复中的作用。该提案的目的是研究抗Nogo-A免疫疗法作为治疗性干预措施，以改善老年啮齿动物中风后记忆力障碍。 AIM 1将采用莫里斯水迷宫来确定中风后抗Nogo-A免疫疗法是否会减弱记忆力障碍。莫里斯水迷宫将用于评估空间参考和工作记忆。 AIM 2将采用高尔基-Cox分析来确定中风后的抗Nogo-A免疫疗法是否会在海马和内嗅皮层中诱导树突状可塑性，这是两种涉及学习和记忆的大脑结构。海马（CA1锥体细胞，Cas锥体细胞和DG颗粒细胞）和内嗅皮层（II层星状细胞，III层III锥体细胞，V层V锥体细胞）的神经元，将通过质量跨度的神经化的塑料溶液和GOLGI cox处理的大脑检查形态学。这些实验与临床实践有关，通过解决中风后记忆障碍引起的生活质量的显着降低，与临床实践有关。此外，通过对老年人人口进行建模，中风最普遍，具有老化的啮齿动物，使这些实验的翻译相关性最大化。此外，抗Nogo-A免疫疗法是一种有希望的治疗干预措施，可以快速转化为中风的临床试验。这是欧洲开始测试抗Nogo-A作为脊髓损伤的治疗干预措施的第一阶段临床试验证明的。中风是美国残疾的主要原因，在许多情况下，残疾是由包括记忆障碍在内的认知障碍造成的。该提案将有助于发展认知障碍的治疗方法，包括中风后记忆障碍。此外，该建议将导致有关神经元可塑性在中风后脑修复中的作用的重要信息。