title: Early life status epilepticus and stress have distinct and sex-specific effects on learning, subsequent seizure outcomes, including anticonvulsant response to phenobarbital.
abstract: OBJECTIVE
  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 (3KA-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
  3KA-SE or maternal separation was induced on postnatal days (PN) 4-6 or 14-16. Rats were tested on Barnes maze (PN16-19), or lithium-pilocarpine SE (PN19) or flurothyl seizures (PN32). The anticonvulsant effects of phenobarbital (20 or 40 mg/kg/rat, intraperitoneally) pretreatment were tested on flurothyl seizures. FluoroJadeB staining assessed hippocampal injury.
  
  
  RESULTS
  3KA-SE or separation on PN4-6 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 3KA-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.
authors.affiliation: Saul R. Korey Department of Neurology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA; Department of Physiology, Faculty of Medicine, Istanbul Bilim University, Istanbul, Turkey.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Akman
authors.forename: Solomon L
authors.initials: SL
authors.lastname: Moshé
authors.forename: Aristea S
authors.initials: AS
authors.lastname: Galanopoulou
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000627:therapeutic use*; D003292:Convulsants / Q000633:toxicity; D004195:Disease Models, Animal; D005260:Female; D005452:Fluoresceins; D007859:Learning Disabilities / Q000209:etiology*; D008297:Male; D008426:Maternal Deprivation; D018782:Maze Learning / Q000187:drug effects; D010634:Phenobarbital / Q000627:therapeutic use*; D011247:Pregnancy; D051381:Rats; D012727:Sex Characteristics; D013226:Status Epilepticus / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy; D013315:Stress, Psychological / Q000175:diagnosis* / Q000188:drug therapy / Q000209:etiology
chemical_list: D000927:Anticonvulsants; D003292:Convulsants; D005452:Fluoresceins; C435731:fluoro jade; D010634:Phenobarbital
keywords: Flurothyl; Infant rat; Lithium-pilocarpine; Phenobarbital; Seizures; Status epilepticus