Cognitive Recovery and Neuronal Plasticity after Stroke in the Aged

描述（由申请人提供）：中风是残疾的主要原因，包括记忆障碍。我们的实验室已经表明，一种新的治疗，抗Nogo-A免疫疗法导致啮齿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被研究。本提案的目的是研究抗Nogo-A免疫疗法作为治疗干预，以改善老年啮齿动物中风后的记忆障碍。目的1采用Morris水迷宫实验研究抗Nogo-A免疫治疗对老年人脑卒中后记忆障碍的影响。Morris水迷宫将用于评价空间参考和工作记忆。目的2将采用Golgi-Cox分析来确定中风后抗Nogo-A免疫治疗是否诱导海马和内嗅皮层中的树突可塑性，这两种大脑结构参与学习和记忆。将通过量化树突状分支、棘密度和棘形态，检查Golgi-Cox处理脑的海马（CA 1锥体细胞、CAS锥体细胞和DG颗粒细胞）和内嗅皮质（II层星状细胞、III层锥体细胞和V层锥体细胞）中的神经元的结构神经元可塑性。这些实验通过解决中风后记忆障碍引起的生活质量显著下降而与临床实践相关。此外，这些实验的翻译相关性最大限度地通过模拟老年人群体，其中中风是最普遍的，与老年啮齿动物。此外，抗Nogo-A免疫疗法是一种有前途的治疗干预，可以迅速转化为中风的临床试验。这一点已在欧洲开始的1期临床试验中得到证实，该试验旨在测试抗Nogo-A作为脊髓损伤的治疗干预。在美国，中风是残疾的主要原因，并且在许多情况下，残疾是由认知障碍（包括记忆障碍）引起的。这一提议将有助于开发中风后认知障碍包括记忆障碍的治疗方法。此外，这一建议将导致重要的信息有关的作用，神经元可塑性脑修复后中风。

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.