IN VIVO IMAGING OF SEIZURE-INDUCED ASTROCYTIC INJURY

癫痫发作引起的星形胶质细胞损伤的体内成像

基本信息

批准号：
8999029
负责人：
MICHAEL WONG
金额：
$ 19.06万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-02-01 至 2017-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8999029
关键词：
Acute Affect Animal Model Astrocytes Atrophic Behavior Disorders Brain Brain Injuries Cells Cessation of life Chronic Cognitive deficits Comorbidity Data Dendrites Dendritic Spines Epilepsy Epileptogenesis Evolution Foundations General Population Gliosis Grant Health High Prevalence Homeostasis Image Immune Impaired cognition Inflammatory Injury Ions Lead Mediating Mental disorders Mus Neuroglia Neurologic Neurons Neurotransmitters Patients Physiological Process Public Health Recovery Research Research Proposals Role Seizures Signal Transduction Specimen Status Epilepticus Structural defect Structure Synapses Testing Therapeutic Intervention Work base cell type cellular imaging clinical application clinically significant extracellular imaging modality improved in vivo in vivo imaging innovation kainate neocortical novel novel therapeutics prevent

项目摘要

DESCRIPTION (provided by applicant): Epilepsy is often associated with disabling comorbidities, including cognitive impairment, psychiatric and behavioral disorders, and other neurological deficits. Seizures themselves may cause brain injury, which might, in part, contribute to these comorbid conditions, as well as promote a progressive process of epileptogenesis leading to worsening seizures. Although neurons remain the principal cells mediating epilepsy and its comorbidities, the role of glia in regulating epileptogenesis and associated brain injury has become increasingly recognized. Recent advances with in vivo imaging demonstrate that astrocytes undergo rapid, dynamic structural changes under a variety of physiological and pathological conditions, including neuronal activity-dependent modulation. However, minimal information is available on rapid, dynamic changes in astrocytes occurring in epileptic states. The primary hypothesis of this research proposal is that seizures cause acute, dynamic structural changes in astrocytes, which correlate with injury to neighboring dendrites. In this grant, we will utilize in vivo multiphoton imaging to assess both the acute and evolving chronic effects of kainate-induced seizures on cortical astrocytes in mice. This proposal is innovative in applying cutting-edge in vivo imaging methods for studying seizure-induced brain injury. This work also has strong clinical significance, as it will lay the foundation for dissectig the underlying mechanistic basis of seizure-induced glial injury and testing rational therapeutic interventions for epilepsy targeting astrocytes.

描述（由适用提供）：癫痫通常与残疾合并症有关，包括认知障碍，精神病和行为障碍以及其他神经系统缺陷。癫痫发作本身可能会导致脑损伤，这可能部分导致了这些合并症，并促进了癫痫发生的逐步逐步导致令人担忧的癫痫发作。尽管神经元仍然是介导癫痫及其合并症的主要细胞，但神经胶质在确定癫痫生成和相关脑损伤中的作用已越来越被识别。体内成像的最新进展表明，星形胶质细胞在各种物理和病理条件下（包括神经元活动依赖性调节）经历了快速的动态结构变化。但是，有关在癫痫状态下发生的星形胶质细胞快速，动态变化的最小信息。该研究提案的主要假设是，癫痫发作会导致星形胶质细胞的急性，动态结构变化，这与邻近的树突相关。在这笔赠款中，我们将利用体内多光子成像来评估海藻酸盐诱导的癫痫发作对小鼠皮质星形胶质细胞的急性和不断发展的慢性作用。该提案在应用体内成像方法中用于研究癫痫发作诱导的脑损伤时具有创新性。这项工作也具有强大的临床意义，因为它将为癫痫发作诱导的神经胶质损伤的基础基础奠定基础，并测试针对靶向星形胶质细胞的癫痫病的有理治疗干预措施。