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 administration of the DNA-alkylating agent methylazoxymethanol acetate (MAM), were subjected to in vitro simulated ischemia or exposed to glutamate (5 mM) or kainate (1 mM). All these neurotoxic insults resulted in decreased viability of the slices, as quantitatively assessed by decrease in the rate of protein synthesis. Hippocampal slices subjected to ischemia and olfactory cortex slices exposed to glutamate or kainate were significantly less sensitive to the neurotoxic insult in microencephalic rats than in controls. The increased efflux of neurotransmitter amino acids (glutamate, aspartate and GABA) in the medium from slices subjected to ischemia or exposed to kainate, showed no significant differences among microencephalic and control rats. The present results suggest that the decreased excitotoxic sensitivity of microencephalic rats is, at least in part, related to intrinsic structural and/or functional alterations of some brain regions which undergo decrease in size as a consequence of the gestational treatment.