Abstracts

RATIONALE: In adults, hippocampal neurogenesis is stimulated by seizures. In contrast, we showed a history of only one or two neonatal seizure(s) is sufficient to dramatically suppress granule cell neurogenesis after a critical developmental period, at a time that coincides with an endogenous surge of glucocorticosteroids. Therefore, to determine whether corticosteroid (CORT) baseline levels may be boosted for a prolonged period by neonatal seizures, plasma CORT levels were examined at times after single or multiple injections of kainic acid (KA) during early postnatal development (at ages: P6, P9, P13 or P20).
METHODS: CORT plasma levels were measured by radioimmunoassay (RIA) before and during the seizure and at time points of the seizure-free period. Brains were processed for bromo-deoxyuridine (BrdU) immunohistochemistry at corresponding ages.
RESULTS: At P6, basal CORT levels were low (554 [plusminus] 250 pg/ml), and increased linearly between P9 and P20. Following one episode of status epilepticus at P6, a biphasic response was observed such that CORT levels escalated rapidly within 30 min, reached a peak by 1 hr (to 13730 [plusminus] 5513 pg/ml) then returned to baseline levels between 3-8 hrs. Half-maximal levels reappeared and persisted for 24-72 hrs. After a series of two KA injections at P6 and P9, CORT levels were elevated when measured 4 days later (65477[plusminus] 3700 vs. controls 32500 [plusminus] 6500). Similar increases in CORT levels were achieved by one KA seizure induced at P20 when measured at 24 hrs (65666 [plusminus] 1939 pg/ml).
CONCLUSIONS: The data suggest that raised circulating levels of CORT during the seizure-free period may contribute to the delayed effects that neonatal seizures have on suppressing granule cell neurogenesis.