title: Acute postischemic seizures are associated with increased mortality and brain damage in adult mice.
abstract: Postischemic seizures are associated with worsened outcome following stroke, but the underlying pathophysiology is poorly understood. Here we examined acute seizures in adult mice following hypoxia-ischemia (HI) via combined behavioral, electrophysiological, and histological assessments. C57BL/6 mice aged 4-9 months received a permanent occlusion of the right common carotid artery and then underwent a systemic hypoxic episode. Generalized motor seizures were observed within 72 h following HI. These seizures occurred nearly exclusively in animals with extensive brain injury in the hemisphere ipsilateral to the carotid occlusion, but their generation was not associated with electroencephalographic discharges in bilateral hippocampal and neocortical recordings. Animals exhibiting these seizures had a high rate of mortality, and post-HI treatments with diazepam and phenytoin greatly suppressed these behavioral seizures and improved post-HI animal survival. Based on these data, we conclude that these seizures are a consequence of HI brain injury, contribute to worsened outcome following HI, and that they originate from deep subcortical structures.
authors.affiliation: Division of Fundamental Neurobiology, Toronto Western Research Institute, University Health Network, Toronto, Ontario, Canada M5T 2S8.
authors.forename: Youssef Hanna
authors.initials: YH
authors.lastname: El-Hayek
authors.forename: Chiping
authors.initials: C
authors.lastname: Wu
authors.forename: Rick
authors.initials: R
authors.lastname: Chen
authors.forename: Abdel Rahman
authors.initials: AR
authors.lastname: Al-Sharif
authors.forename: Shelley
authors.initials: S
authors.lastname: Huang
authors.forename: Nisarg
authors.initials: N
authors.lastname: Patel
authors.forename: Chao
authors.initials: C
authors.lastname: Du
authors.forename: Crystal Ann
authors.initials: CA
authors.lastname: Ruff
authors.forename: Michael G
authors.initials: MG
authors.lastname: Fehlings
authors.forename: Peter L
authors.initials: PL
authors.lastname: Carlen
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D004569:Electroencephalography; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D020925:Hypoxia-Ischemia, Brain / Q000150:complications* / Q000473:pathology* / Q000503:physiopathology; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012640:Seizures / Q000209:etiology* / Q000473:pathology* / Q000503:physiopathology