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Dystrophic functions of aged astrocytes following traumatic brain injury

创伤性脑损伤后老化星形胶质细胞的营养不良功能

基本信息

批准号：
9434350
负责人：
Josh Morganti
金额：
$ 22.95万
依托单位：
UNIVERSITY OF KENTUCKY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-30 至 2020-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9434350
关键词：
Acute Adult Affect Age Aging Alzheimer&apos s Disease Animals Astrocytes Behavioral Biological Response Modifiers Brain Brain Injuries CCL2 gene Cell Separation Chemotactic Factors Chronic Cognitive Data Dementia Development Disease Environment Environmental Risk Factor Epidemic Experimental Designs Flow Cytometry Gene Expression Genes Glial Fibrillary Acidic Protein Goals Healthcare Healthcare Systems Impaired cognition Incidence Individual Inflammation Inflammatory Inflammatory Response Injections Injury Knowledge Leukocytes Light Link Magnetism Measures Mediating Microglia Modeling Molecular Molecular Profiling Mus Myelogenous Nerve Degeneration Neurodegenerative Disorders Neurons Outcome Outcome Measure Parkinson Disease Pathologic Pathology Pathway interactions Peripheral Population Production Radial Recovery of Function Research Design Resolution Risk Risk Factors Rodent Role Severities Signal Transduction Stimulus Survivors Synapses Therapeutic Therapeutic Intervention Time Traumatic Brain Injury Traumatic Brain Injury recovery United States Water age effect aged aging brain aging population arm cognitive function controlled cortical impact cytokine demographics improved inflammatory milieu injured knowledge base macrophage monocyte nano-string neurotoxic novel prevent recruit response response to injury restoration targeted treatment therapeutic target transcription factor young adult

项目摘要

The broad and long-term goals of this proposal are to form a significant knowledge-base surrounding the role aged astrocytes in the propogation of neurodegenerative sequelae after TBI. TBI in the aged population represents a significant unmet healthcare challenge, as advanced aging is the greatest risk factor for acquiring a TBI, and subsequently developing neurodegenerative disease such as dementia, Alzheimer’s- and Parkinson’s disease. Cumulatively, the research design takes advantage of specific inflammatory hallmarks and functional modulators associated with dystrophic astrocytes, in an attempt to delineate their respective contributions to neuronal pathology and cognitive dysfunction. Ultimately, we will determine if harnessing astrocytes via novel AAV constructs in aged TBI models is associated with improving neuronal and cognitive outcome measures.

该提案的广泛和长期目标是形成一个重要的知识库围绕老化星形胶质细胞在 TBI 后神经退行性后遗症传播中的作用。随着先进技术的发展，老年人群中的 TBI 代表了一个重大的未满足的医疗保健挑战衰老是发生 TBI 并随后发展为 TBI 的最大风险因素神经退行性疾病，例如痴呆症、阿尔茨海默病和帕金森病。总的来说，研究设计利用了特定的炎症标志和与营养不良的星形胶质细胞相关的功能调节剂，试图描绘它们的对神经元病理学和认知功能障碍的各自贡献。最终，我们将确定在老年 TBI 模型中通过新型 AAV 构建体利用星形胶质细胞是否相关改善神经元和认知结果测量。