ABSENCE OF EXCITOTOXIC NEUROPATHOLOGY IN MICROENCEPHALIC RATS AFTER SYSTEMIC KAINIC ACID ADMINISTRATION

We have s.c. injected with kainic acid (12 mg/kg) normal adult rats as well as rats rendered microencephalic by selectively timed administra tion of the DNA alkylating agent methylazoxymethanol acetate (MAM) to the mother during pregnancy. Histological examination of the brains re vealed that normal animals underwent neurodegeneration in brain region s sensitive to kainic acid excitotoxicity, such as the olfactory corte x and the hippocampus, while no damage was apparent in the same region s of microencephalic rats. Evaluation of the neurotoxic outcome conseq uent to the excitotoxic stimulation, was quantitatively performed by m easuring the levels of appropriate neurochemical markers 15 days after kainic acid injection. In normal animals, this resulted in significan t decrease (up to 60% in the olfactory cortex and 30% in the hippocamp us) of markers related to glutamatergic and GABAergic neurons, whereas in MAM-treated rats the same markers were not significantly affected, thus demonstrating a substantial protection against the excitotoxic i nsult in the microencephalic condition.