Age-dependent effects of glutamate toxicity in the hippocampus

Abstract

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 animals. The reasons for this age-related phenomenon are unclear. Since seizure-induced cell death may be due to the neurotoxic effects of excessive glutamate release, we tested the hypothesis that the immature brain is less vulnerable to glutamate-induced neurotoxicity than the mature brain. We administered equal amounts of glutamate (0.5 μmol in 1.0 μl) unilaterally into the CA1 subfield of the hippocampus of rats at postnatal (P) days 10, 20, 30, and 60. Equal volumes of saline were injected in the contralateral hippocampus. Rats were killed 7 days later 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 P20 rats were smaller than those at P30 and P60, which were similar in extent. This study demonstrates that the extent of glutamate neurotoxicity in the hippocampus is highly age-dependent, with immature hippocampi relatively resistant to glutamate-induced cell death.