MICROGLIAL RESPONSE TO N-METHYL-D-ASPARTATE-MEDIATED EXCITOTOXICITY IN THE IMMATURE RAT-BRAIN

The intracerebral injection of N-methyl-D-aspartate (NMDA) has been pr oposed as a model for hypoxic-ischemic insult in the immature brain. I n this light, the aim of this study was to describe the time course of the microglial reaction in the areas undergoing primary degeneration at the site of intracortical NMDA injection as well as in areas underg oing secondary anterograde and/or retrograde degeneration. Fifty nanom oles of NMDA were injected in the sensorimotor cortex of 6-day-old rat s. After survival times ranging from 10 hours to 28 days, cryostat sec tions were stained for routine histology and for the demonstration of microglial cells by means of tomato lectin histochemistry. The areas a ffected by primary degeneration caused by the intracortical injection of NMDA were the neocortex, the hippocampus, and the rostral thalamus. Secondary degeneration (retrograde and anterograde) was observed in t he ventrobasal complex of the thalamus. The cortical lesion also cause d Wallerian degeneration of the cortical descending efferents as obser ved in the basilar pens. Microglial reactivity in all these areas was present at 10 hours postinjection and was restricted to the areas unde rgoing neuronal or axonal degeneration. Reactive microglial cells were stained intensely and showed a round or pseudopodic morphology. At 3 days, an apparent increase in the number of tomato lectin-positive cel ls was observed in the areas undergoing neuronal death. By 7 days afte r the injection, the lesion became nonprogressive, and by 14 and 28 da ys, microglial cells showed moderate lectin binding and a more ramifie d morphology. (C) 1996 Wiley-Liss, Inc.