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 potassium concentration, all of which alter neuronal function, was studied in hippocampal slices. The activation of microglia was detected by immunostaining with a monoclonal antibody (OX-42) raised against a type 3 complement receptor (CD11b). During activation the phenotype of microglia changes and the intensity of staining of individual cells increases. Oxygen deprivation depressed the focal responses of CA1 neurons to stratum radiatum volleys. Microglial activation was time dependent. Ten minute hypoxia caused mild activation, and after 20 min, a strong microglial reaction could be observed. Although neuronal function returned during reoxygenation, the morphological signs of microglial activation remained. Epileptiform activity of hippocampal neurons, 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 induced microglial changes similar to those induced by hypoxia and kainic acid. It is therefore suggested that an elevated extracellular potassium ion concentration may be the common factor in microglial activation observed in these experiments since this is raised both in hypoxia and under the effect of excitotoxins.