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 administration of the DNA alkylating agent methylazoxymethanol acetate (MAM) to the mother during pregnancy. Histological examination of the brains revealed that normal animals underwent neurodegeneration in brain regions sensitive to kainic acid excitotoxicity, such as the olfactory cortex and the hippocampus, while no damage was apparent in the same regions of microencephalic rats. Evaluation of the neurotoxic outcome consequent to the excitotoxic stimulation, was quantitatively performed by measuring the levels of appropriate neurochemical markers 15 days after kainic acid injection. In normal animals, this resulted in significant decrease (up to 60% in the olfactory cortex and 30% in the hippocampus) 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 insult in the microencephalic condition.