ISCHEMIC AND EXCITOTOXIC DAMAGE TO BRAIN-SLICES FROM NORMAL AND MICROENCEPHALIC RATS

Brain slices (olfactory cortex, fronto-parietal cortex and hippocampus ) taken from normal or microencephalic rats, obtained by gestational a dministration of the DNA-alkylating agent methylazoxymethanol acetate (MAM), were subjected to in vitro simulated ischemia or exposed to glu tamate (5 mM) or kainate (1 mM). AU these neurotoxic insults resulted in decreased viability of the slices, as quantitatively assessed by de crease in the rate of protein synthesis. Hippocampal slices subjected to ischemia and olfactory cortex slices exposed to glutamate or kainat e were significantly less sensitive to the neurotoxic insult in microe ncephalic rats than in controls. The increased efflux of neurotransmit ter amino acids (glutamate, aspartate and GABA) in the medium from sli ces subjected to ischemia or exposed to kainate, showed no significant differences among microencephalic and control rats. The present resul ts suggest that the decreased excitotoxic sensitivity of microencephal ic rats is, at least in part, related to intrinsic structural and/or f unctional alterations of some brain regions which undergo decrease in size as a consequence of the gestational treatment. (C) 1997 Elsevier Science Ireland Ltd.