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: 7331811
• 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/7331811
• 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）：中风是导致残疾（包括记忆障碍）的主要原因。我们的实验室已经证明，一种新的治疗方法——抗 Nogo-A 免疫疗法可以使啮齿类动物中风后感觉运动功能恢复。然而，抗Nogo-A免疫疗法在中风后记忆恢复中的作用尚未得到研究。本提案的目的是研究抗 Nogo-A 免疫疗法作为一种治疗干预措施，以改善老年啮齿动物中风后的记忆障碍。目标 1 将利用 Morris 水迷宫来确定老年人中风后抗 Nogo-A 免疫疗法是否可以减轻记忆障碍。莫里斯水迷宫将用于评估空间参考和工作记忆。目标 2 将采用高尔基考克斯分析来确定中风后的抗 Nogo-A 免疫疗法是否会诱导海马体和内嗅皮层（涉及学习和记忆的两种大脑结构）的树突可塑性。高尔基-考克斯处理大脑的海马神经元（CA1锥体细胞、CAS锥体细胞和DG颗粒细胞）和内嗅皮层（第二层星状细胞、第三层锥体细胞和第五层锥体细胞）的神经元将通过树突分枝、脊柱密度和脊柱的量化来检查结构神经元可塑性 形态学。这些实验通过解决中风后记忆障碍引起的生活质量显着下降的问题，与临床实践相关。此外，通过用老年啮齿动物对中风最常见的老年人群进行建模，可以最大限度地提高这些实验的转化相关性。此外，抗Nogo-A免疫疗法是一种有前途的治疗干预措施，可以快速转化为中风的临床试验。欧洲已开始测试抗 Nogo-A 作为脊髓损伤治疗干预措施的 1 期临床试验就证明了这一点。在美国，中风是导致残疾的主要原因，在许多情况下，残疾是由认知障碍（包括记忆障碍）造成的。该提案将有助于开发治疗认知障碍（包括中风后记忆障碍）的方法。此外，该提议还将带来有关神经元可塑性在中风后大脑修复中的作用的重要信息。