Open AccessEarly Life Status Epilepticus and Stress Have Distinct and Sex‐Specific Effects on Learning, Subsequent Seizure Outcomes, Including Anticonvulsant Response to Phenobarbital
Author(s) -
Akman Ozlem,
Moshé Solomon L.,
Galanopoulou Aristea S.
Publication year - 2015
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12335
Subject(s) - status epilepticus , phenobarbital , anticonvulsant , pilocarpine , epilepsy , kainic acid , hippocampal formation , medicine , anesthesia , psychology , endocrinology , pharmacology , neuroscience , glutamate receptor , receptor
Summary Aims Neonatal status epilepticus ( SE ) is often associated with adverse cognitive and epilepsy outcomes. We investigate the effects of three episodes of kainic acid‐induced SE (3 KA ‐ SE ) and maternal separation in immature rats on subsequent learning, seizure susceptibility, and consequences, and the anticonvulsant effects of phenobarbital, according to sex, type, and age at early life (EL) event. Methods 3 KA ‐ SE or maternal separation was induced on postnatal days ( PN ) 4–6 or 14–16. Rats were tested on Barnes maze ( PN 16–19), or lithium–pilocarpine SE ( PN 19) or flurothyl seizures ( PN 32). The anticonvulsant effects of phenobarbital (20 or 40 mg/kg/rat, intraperitoneally) pretreatment were tested on flurothyl seizures. FluoroJadeB staining assessed hippocampal injury. Results 3 KA ‐ SE or separation on PN 4–6 caused more transient learning delays in males and did not alter lithium–pilocarpine SE latencies, but aggravated its outcomes in females. Anticonvulsant effects of phenobarbital were preserved and potentiated in specific groups depending on sex, type, and age at EL event. Conclusions Early life 3 KA ‐ SE and maternal separation cause more but transient cognitive deficits in males but aggravate the consequences of subsequent lithium–pilocarpine SE in females. In contrast, on flurothyl seizures, EL events showed either beneficial or no effect, depending on gender, type, and age at EL events.