title: Distinct behavioral and epileptic phenotype differences in 129/P mice compared to C57BL/6 mice subject to intraamygdala kainic acid-induced status epilepticus.
abstract: Animal models of status epilepticus are important tools to understand the pathogenesis of epileptic brain injury and evaluate potential seizure-suppressive, neuroprotective, and antiepileptogenic treatments. Focal elicitation of status epilepticus by intraamygdala kainic acid in mice produces unilateral hippocampal damage and the emergence of spontaneous recurrent seizures after a short latent period. The model has been characterized in C57BL/6, BALB/c, and SJL mice where strain-specific differences were found in the extent of hippocampal damage. 129/P mice are a common background strain for genetic models and may display unique characteristics in this model. We therefore compared responses to intraamygdala kainic acid between 129/P and C57BL/6 mice. Racine scale-scored convulsive behavior during status epilepticus was substantially lower in 129/P mice compared with that in C57BL/6 mice. Analysis of surface-recorded electroencephalogram (EEG) showed differences between strains in several frequency bands; EEG total power was greater during ictal episodes while duration of seizures was slightly shorter in 129/P mice. Histological analysis revealed similar hippocampal injury between strains, with neuronal death mainly confined to the ipsilateral CA3 subfield. Expression of genes associated with gliosis and neuroinflammatory responses was also similar between strains after seizures. Video-EEG telemetry recordings showed that 129/P mice first display spontaneous seizures within a few days of status epilepticus similar to C57BL/6 mice. However, high mortality in 129/P mice prevented a quantitative comparison of the epileptic seizure phenotypes between strains. This study defined behavioral, EEG, and histopathologic features of this mouse strain in a model increasingly useful for the study of the genetic contribution to acquired epilepsy. Intraamygdala kainic acid in 129/P mice could serve as a model of nonconvulsive status epilepticus, but long-term assessments will require model adjustment to mitigate the severity of the emergent epileptic phenotype.
authors.affiliation: Department of Physiology & Medical Physics, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin, 2, Ireland.
authors.forename: Luiz Fernando
authors.initials: LF
authors.lastname: Almeida Silva
authors.affiliation: Department of Physiology & Medical Physics, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin, 2, Ireland.
authors.forename: Tobias
authors.initials: T
authors.lastname: Engel
authors.affiliation: Department of Physiology & Medical Physics, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin, 2, Ireland.
authors.forename: Cristina R
authors.initials: CR
authors.lastname: Reschke
authors.affiliation: Division of Population Health Sciences, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin, 2, Ireland.
authors.forename: Ronan M
authors.initials: RM
authors.lastname: Conroy
authors.affiliation: Department of Physiology & Medical Physics, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin, 2, Ireland.
authors.forename: Elena
authors.initials: E
authors.lastname: Langa
authors.affiliation: Department of Physiology & Medical Physics, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin, 2, Ireland. Electronic address: dhenshall@rcsi.ie.
authors.forename: David C
authors.initials: DC
authors.lastname: Henshall
mesh_terms: D000679:Amygdala / Q000187:drug effects*; D000818:Animals; D001522:Behavior, Animal; D004195:Disease Models, Animal; D004569:Electroencephalography; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007608:Kainic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D013226:Status Epilepticus / Q000139:chemically induced* / Q000503:physiopathology*
chemical_list: D018690:Excitatory Amino Acid Agonists; D007608:Kainic Acid
keywords: Animal model; Electroencephalogram; Epileptogenesis; Genetic background; Hippocampal sclerosis