MECHANISMS OF CYTOTOXIC BRAIN EDEMA

细胞毒性脑水肿的机制

• 批准号: 3406448
• 负责人: JAMES E OLSON
• 金额: $ 10.06万
• 依托单位: WRIGHT STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-01 至 1990-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3406448
• 关键词: Reye's syndrome; astrocytes; biological fluid transport; body fluid osmolarity; brain edema; cerebral ischemia /hypoxia; cytotoxicity; electrolyte balance; electrolytes; laboratory rat; membrane channels; membrane permeability; tissue /cell culture

Brain swelling is a critical factor contributing to the mortality and morbidity of individuals with a wide variety of pathologic conditions. The astrocyte is thought to be important in maintaining water volume and electrolyte concentrations and the extracellular space of the brain. The goals of this research proposal include establishing more definitely this critical role of the astrocyte and investigating mechanisms by which this cell achieves net movement of water and solute. A third goal is to determine the relationship between this cell function and the pathogenesis of cytotoxic edema. Cell volume responses of primary cultured astrocytes to altered osmolarity will be studied as a model of astrocyte control of brain water. Techniques developed previously in this laboratory will be refined to permit quantitative measures of water and ion movements during hyper- and hypo-osmotic exposure. The contributions of various ion channels and transport systems to these volume responses will be identified. Finally, we shall study the effects on astrocyte volume regulation of factors which may contribute to the pathogenesis of cytotoxic edema in Reye's Syndrome and cerebral ischemia. We shall correlate these in vitro studies with in vivo states of cerebral edema by quantifying water and ion movements in the brains of animals exposed to those agents which affect astrocyte volume control in vitro. These studies will provide insight into the mechanisms of astrocyte volume control under physiological conditions and the processes important in the genesis and resolution of brain edema in pathologic conditions. Knowledge of these mechanisms will provide testable hypotheses relating to the production and resolution of brain edema in critical clinical states including Reye's Syndrome and cerebral ischemia. In addition, these studies may suggest rational therapies for cytotoxic brain edema.

脑肿胀是导致死亡率和 具有多种病理状况的个体的发病率。 这 星形胶质细胞被认为在维持水量和 电解质浓度和大脑的细胞外空间。 这 这项研究建议的目标包括确定这一点 星形胶质细胞和研究机制的关键作用 细胞实现水和溶质的净运动。 第三个目标是 确定该细胞功能与发病机理之间的关系 细胞毒性水肿。 原代培养星形胶质细胞的细胞体积反应 要改变渗透性，将研究作为星形胶质控制的模型 脑水。 以前在该实验室开发的技术将是 精制以允许对水和离子运动进行定量测量 超渗透性暴露。 各种离子的贡献 这些音量响应的渠道和运输系统将是 确定。 最后，我们将研究对星形胶质细胞体积的影响 调节可能有助于细胞毒性发病机理的因素的调节 Reye综合征和脑缺血的水肿。 我们将将这些关联 通过量化水的体外体内研究的体外研究 以及暴露于那些动物的大脑中的离子运动 在体外影响星形胶质细胞体积控制。 这些研究将洞悉星形胶质细胞体积的机理 在生理条件下的控制和在 病理条件下脑水肿的起源和分辨率。 知识 这些机制将提供与 关键临床状态下脑水肿的生产和分辨 包括雷耶综合症和脑缺血。 另外，这些 研究可能表明细胞毒性脑水肿的合理疗法。