AGE-DEPENDENT EFFECTS OF GLUTAMATE TOXICITY IN THE HIPPOCAMPUS

While prolonged seizures can cause brain damage at any age, the extent of brain damage following prolonged seizures is highly age-dependent. Seizures in the immature brain are followed by far less histological damage than seizures of similar duration and intensity in mature anima ls. The reasons for this age-related phenomenon are unclear. Since sei zure-induced cell death may be due to the neurotoxic effects of excess ive glutamate release, we tested the hypothesis that the immature brai n is less vulnerable to glutamate-induced neurotoxicity than the matur e brain. We administered equal amounts of glutamate (0.5 mu mol in 1.0 mu l) unilaterally into the CA1 subfield of the hippocampus of rats a t postnatal (P) days 10, 20, 30, and 60. Equal volumes of saline were injected in the contralateral hippocampus. Rats were killed 7 days lat er and their brains were examined for hippocampal cell loss. The size of the resultant hippocampal lesion was highly age-dependent. Minimal cell loss was noted in the P10 rats; lesions in the P10 rats were smal ler than those at P30 and P60, which were similar in extent. This stud y demonstrates that the extent of glutamate neurotoxicity in the hippo campus is highly age-dependent, with immature hippocampi relatively re sistant to glutamate-induced cell death.