SOURCES AND EFFECTS OF REACTIVE OXYGEN INTERMEDIATES IN THE BRAIN

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Experiments have been performed on microglia, the resident macrophage in the central nervous system (CNS) cultured from rat cerebral cortex. We have previously shown that these activated cells produce the superoxide radical anion, a reactive oxygen species (ROS). ROS also includes the hydroxyl radical and hydrogen peroxide. Earlier, we found that calcium ions can enter microglial cells when these cells are hyperpolarized. We have continued our studies using the patch-clamp technique in cultured microglial cells on the L-type voltage-dependent calcium channels which open when these cells become depolarized. These channels may play a role in our finding that potassium can modulate the production of the superoxide radical anion from microglial cells. We are also continuing our studies with iron toxicity and its relationship to the production of the highly toxic hydroxyl radical. Survival of dopaminergic neurons grown in the presence of glutathione peroxidase show more diffuse neuronal branching, indicating that hydrogen peroxide is involved.