MOLECULAR MECHANISM AND METABOLIC BASIS OF CELLULAR (CYTOTOXIC) EDEMA

细胞（细胞毒性）水肿的分子机制和代谢基础

• 批准号: 3738217
• 负责人: PAK H CHAN
• 金额: --
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3738217
• 关键词: NMDA receptors; antioxidants; arachidonate; astrocytes; brain edema; brain injury; brain metabolism; carbon; cellular pathology; cerebral ischemia /hypoxia; cytotoxicity; electron microscopy; fatty acid metabolism; free radical oxygen; genetically modified animals; glucose metabolism; glutamate receptor; glutamates; high performance liquid chromatography; immunocytochemistry; inhibitor /antagonist; inositol phosphates; laboratory mouse; laboratory rat; mixed tissue /cell culture; neurons; phase contrast microscopy; phospholipase A2; phospholipase C; phospholipase inhibitor; radionuclides; radiotracer; receptor binding; superoxide dismutase; tissue /cell culture

Cellular (cytotoxic) edema is characterized by swelling of all the cellular elements of the brain (neurons, glia and endothelial cells) with a concomitant reduction in the volume of the brain's extracellular space. Irreversible neuronal swelling characteristically precedes cell death in vitro when the cultured neurons are exposed to glutamate, arachidonic acid, hypoxia or "ischemia". We have hypothesized that oxygen radicals are key mediators or injury factors responsible for the amplification of glutamate and arachidonic acid toxicity in cultured neurons. To test this hypothesis and to determine how and why cells swell under pathological conditions, primary cell cultures of neurons and astrocytes of rats and mice will be used to elucidate the mechanisms that underly NMDA and non-NMDA receptor-mediated cellular swelling and injury. The interaction of receptor mediated swelling with the effects of oxygen radical will also be delineated. Our long-term goal of this study is to employ primary cell cultured obtained from transgenic mice with overexpression of human superoxide dismutase and cells with modified levels of endogenous antioxidants to address the question of whether superoxide radicals are the final common mediators linking glutamate and arachidonic acid in their biochemical expression of toxicity in neurons and astrocytes.

细胞（细胞毒性）水肿的特征是所有细胞肿胀