MOLECULAR MECHANISM AND METABOLIC BASIS OF CELLULAR (CYTOTOXIC) EDEMA

细胞(细胞毒性)水肿的特征是所有细胞肿胀。 大脑的元素(神经元、神经胶质细胞和内皮细胞) 随之而来的是大脑细胞外空间的体积减少。 不可逆的神经元肿胀特征先于细胞死亡 当培养的神经元暴露在谷氨酸，花生四烯酸， 缺氧或“缺血”。我们假设氧自由基是关键 谷氨酸放大的介质或损伤因素 和花生四烯酸对培养神经元的毒性。 为了验证这一假设，并确定细胞如何以及为什么在 神经细胞和星形胶质细胞的病理条件、原代细胞培养 大鼠和小鼠将被用来阐明NMDA不足的机制 以及非NMDA受体介导的细胞肿胀和损伤。这个 受体介导的溶胀与氧效应的相互作用 激进分子也将被描绘出来。我们这项研究的长期目标是 利用从转基因小鼠获得的原代培养细胞 人超氧化物歧化酶的过表达及其修饰细胞 内源性抗氧化剂来解决超氧化物 自由基是连接谷氨酸和花生四烯酸的最终常见媒介 酸性物质在其生化表达中对神经元和星形胶质细胞具有毒性。

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.