Stress within the postseizure time window inhibits seizure recurrence

Recurrence is a key characteristic in the development of epilepsy. It remains unclear whether seizure recurrence is sensitive to postseizure stress. Here, tonic-clonic seizures were induced with a convulsive dose of pentylenetetrazole (PTZ), and acute seizure recurrence was evoked with a subconvulsive dose of the drug. We found that stress inhibited seizure recurrence when applied 30 minutes or 2 hours, but not 4 hours, after the tonic-clonic seizure. The time-dependent anti-recurrence effect of stress was mimicked by the stress hormone corticosterone and blocked by co-administration of mineralocorticoid and glucocorticoid receptor antagonists. Furthermore, in a PTZ-induced epileptic kindling model, corticosterone administered 30 minutes after each seizure decreased the extent of seizures both during the kindling establishment and in the following challenge test. These results provide novel insights into both the mechanisms of and therapeutic strategies for epilepsy. (C) 2010 Elsevier Inc. All rights reserved.

We thank Professors Wendy Grus, Peng Shi, Soochin Cho, and Oliver A. Ryder for valuable comments. This work was supported by grants from the State Key Basic Research and Development Plan (2007CB411600); National Natural Science Foundation of China (U0836603 and 30621092); National Undergraduate Students Research Training Fund from Ministry of Education of the People's Republic of China; National Fund for Fostering Talents of Basic Science (Grant No. J0730652); Research Training Fund from Experiment Teaching Center of Life Sciences; and Project of Higher Education Reform and Practice of Science and Engineering from Ministry of Education of the People's Republic of China (Grant No. 239).