Ibotenate-induced neuronal degeneration in immature rat brain

Stereotaxic microinjections of the excitotoxin, ibotenic acid, were made into the striatum, hippocampus or cerebellum of the immature (7-day-old) rat. Two days later, pups were decapitated and the brains processed for light microscopic examination or neurochemical analyses. 10 micrograms ibotenate caused a complete loss of nerve cell bodies throughout the striatum and hippocampus while intracerebellar injections produced no detectable damage. In the striatum, catecholamine histofluorescence was abolished and dopamine uptake severely reduced, indicating also a loss of afferent nerve terminals. Co-injection of 10 micrograms ibotenate with equimolar amounts of the selective amino acid antagonist, (-)-2-amino-7-phosphonoheptanoic acid, resulted in the protection of both striatal cell bodies and dopaminergic nerve terminals. The neurotoxic properties of ibotenate described here are in marked contrast to those of kainic acid, a related excitotoxin. Differences in the ontogenetic pattern of receptors which mediate neurodegenerative events may account for the pharmacological and regional selectivity and the partial lack of axon-sparing properties of ibotenic acid lesions in the immature brain.