SHORT-TERM AND LONG-TERM EFFECTS OF EARLY SEIZURES ON DEVELOPING BRAIN

Objective: To study the short-term and long-term effect of early life seizure on immature brain.

Methods: We established two seizure models: flurothyl inhalation induced seizure (Postnatal day 6) (in vivo model) and magnesium-free treatment induced epileptiform discharge in cultured rat embryonic cortical neurons (in vitro model). Routine molecular biological and electrophysiological methods were used to evaluate the neuronal injury induced by the seizures.

Results: Seizure induced injury of cultured developmental cortical neurons was mainly functional without obvious cell loss; relative immature neurons displayed milder mitochondria function impairment than that of mature neurons. Intracellular [Ca2+] ([Ca2+]i) of neurons was changed either for short time or for long time; IL-1ra can rescue the [Ca2+]i changes either for the short time or for the long time after the seizures. After transient Mg2±free treatment, NMDA receptor subunits mRNA and protein expressions were changed for a long time, and the changes were different between neurons cultured for 6d and for 17d, and MTT conversion rates were decreased for 1 week. The latencies to develop generalized tonic seizures induced by PTZ was reduced in the adult rats who had the early life seizures. The escape latencies from the Morris water maze test of the rats in the recurrent-seizure group were significantly longer than those of the control rats, but there was no difference between the single-seizure group and the control group.

Conclusion: The early-life seizures do have both the short-term and long-term influence on immature rat brain.

Keywords: Seizure, development, brain, NMDA, [Ca2+]i