MECHANISMS OF CYTOTOXIC BRAIN EDEMA

细胞毒性脑水肿的机制

• 批准号: 3406445
• 负责人: JAMES E OLSON
• 金额: $ 23.84万
• 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 1994-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3406445
• 关键词: Reye's syndrome; astrocytes; biological fluid transport; blood brain barrier; body fluid osmolarity; brain edema; cell morphology; cerebral ischemia /hypoxia; cytotoxicity; electrolyte balance; electrolytes; hepatic coma /encephalopathy; homeostasis; laboratory rat; membrane channels; membrane permeability; solute; tissue /cell culture

DESCRIPTION (Adapted from Investigator's Abstract): Brain edema 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 in the extracellular space of the brain. The goals of this research project are to understand more definitely the mechanisms by which this cell achieves net movement of water and solute and the relationship between this cell function and the pathogenesis of cytotoxic edema. Cell volume and metabolic responses of astrocytes to conditions of altered osmolarity will be correlated with movements of ions and putative "idiogenic" amino acid osmolytes. The contributions of various ion channels and transport systems to these volume responses will be defined. The control of intracellular calcium of ion movements induced by antiosmotic exposure will be explored. Finally, the effects of astrocyte volume regulation and solute transport of factors which may contribute to cytotoxic edema in Reye's syndrome, hepatic encephalopathy, and conditions of reduced brain energy metabolic state such as ischemia will be studied. In in vivo studies, the ability of the brain to maintain water homeostasis will be quantified. Blood-brain barrier integrity will be determined and solute movements which contribute to water homeostasis in normal rats and rats subjected to states of cerebral edema will be compared with in vitro studies of astrocytes. These studies will provide a greater understanding of the mechanisms of astrocyte volume regulation under physiologic conditions and the processes responsible for the genesis and resolution of brain edema in pathologic states. Knowledge of these mechanisms will provide new testable hypotheses relating to the development and resolution of brain edema in critical clinical states including Reye's syndrome, hepatic encephalopathy, and ischemia. These studies also may suggest rational therapies for cytotoxic brain edema.

描述（根据研究者的摘要改编）：大脑水肿是 导致个人死亡率和发病率的关键因素 具有多种病理状况。 星形胶质细胞被认为 对于维持水量和电解质浓度很重要 大脑的细胞外空间。 该研究项目的目标 更了解该单元的机制 实现水和溶质的网络移动以及这之间的关系 细胞功能和细胞毒性水肿的发病机理。 细胞体积和 星形胶质细胞对改变渗透压的条件的代谢反应将 与离子的运动和推定的“定期”氨基酸相关 渗透。 各种离子渠道和运输系统的贡献 对这些卷响应将被定义。 细胞内的控制 将探索由抗渗透性暴露引起的离子运动的钙。 最后，星形胶质细胞体积调节和溶质转运的影响 可能导致Reye综合征细胞毒性水肿的因素，肝 脑病和降低脑能量代谢状态的条件 由于缺血将被研究。 在体内研究中，大脑的能力 维持水的稳态将被量化。 血脑屏障 将确定完整性并求解有助于水的运动 正常大鼠和受脑水肿状态的大鼠体内平衡 将与星形胶质细胞的体外研究进行比较。 这些研究将对机制有更深入的了解 在生理条件下的星形胶质细胞体积调节和过程 负责病理学中脑水肿的起源和解决 国家。 这些机制的知识将提供新的可检验的假设 与关键的大脑水肿的发展和解决有关 临床状态包括雷耶综合症，肝脑病和 缺血。 这些研究还可能表明细胞毒性的合理疗法 脑水肿。