ACTIVATED MICROGLIAL CELLS MIGRATE TOWARDS SITES OF EXCITOTOXIC NEURONAL INJURY INSIDE ORGANOTYPIC HIPPOCAMPAL SLICE CULTURES

The aim of this study was to analyse microglial reactions to excitotox ic N-methyl-D-aspartic acid (NMDA)-induced degeneration of rat dentate and hippocampal neurons in vitro. We used a migration model combining the techniques of microglial single cell culture and organotypic hipp ocampal slice culture (OHSC). Site-specific oxidative damage in OHSCs was induced by pretreatment with 50 mu M NMDA, Neuronal injury determi ned by propidium iodide (PI) uptake included the hippocampal cell laye rs df the dentate gyrus (DC) and the cornu ammonis (CA). Fluorescence- prelabelled microglial cells with ameboid morphology were transferred onto the OHSC and migrated predominantly to the prelesioned cell layer s of DG and CA when compared with unlesioned areas of the OHSC. In NMD A pretreated slices, microglial cells clustered around degenerating gr anule cells in the DG and pyramidal cells in the CA. This effect was s ignificantly inhibited in unlesioned slice cultures and in NMDA-expose d cultures that were pretreated with the NMDA-antagonist MK-801. Our o bservations suggest that microglia - attracted by the presence of stim uli provided by NMDA-induced neuronal death - migrate specifically tow ards these lesioned neurons.