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

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.