Rapid activation of microglial cells by hypoxia, kainic acid, and potassium ions in slice preparations of the rat hippocampus

Microglial activation induced by hypoxia, kainic acid and elevated potassiu m concentration, all of which alter neuronal function, was studied in hippo campal slices. The activation of microglia was detected by immunostaining w ith a monoclonal antibody (OX-42) raised against a type 3 complement recept or (CD11b). During activation the phenotype of microglia changes and the in tensity of staining of individual cells increases. Oxygen deprivation depre ssed the focal responses of CA1 neurons to stratum radiatum volleys. Microg lial activation was time dependent. Ten minute hypoxia caused mild activati on, and after 20 min, a strong microglial reaction could be observed. Altho ugh neuronal function returned during reoxygenation, the morphological sign s of microglial activation remained. Epileptiform activity of hippocampal n eurons, followed by depression. was induced by application of 0.5 mM kainic acid, in a time and dose dependent manner. Washing out kainic acid did not alter microglial reaction. Elevated concentrations of potassium ions induc ed microglial changes similar to those induced by hypoxia and kainic acid. It is therefore suggested that an elevated extracellular potassium ion conc entration may be the common factor in microglial activation observed in the se experiments since this is raised both in hypoxia and under the effect of excitotoxins, (C) 2001 Elsevier Science B.V. All rights reserved.