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 cultured from cerebral cortices of rat. We have previously shown that these activated cells produce the superoxide radical anion, a reactive oxygen species (ROS). ROS include also the hydroxyl radical and hydrogen peroxide. The resting concentration of intracellular calcium in the microglial cell is about 100 nM. When the calcium ionophore, A23187, is added to the tissue media, superoxide radical anions are released from the microglia. The maximum intracellular calcium that can be reached by this calcium ionophore is about 300 nM. We have shown that beta~A4 peptide, a part of the larger amyloid precursor protein, is aggregated into large, multiple~sized fragments in the presence of activated microglia and certain other peptides.