Early-onset convulsive seizures induced by brain hypoxia-ischemia in aging mice: effects of anticonvulsive treatments

Thumbnail Image
Wang, Justin
Wu, Chiping
Peng, Jessie
Patel, Nisarg
Huang, Yayi
Gao, Xiaoxing
Aljarallah, Salman
Eubanks, James H.
McDonald, Robert J.
Zhang, Liang
Journal Title
Journal ISSN
Volume Title
Public Library of Science
Aging is associated with an increased risk of seizures/epilepsy. Stroke(ischemic or hemorrhagic) and cardiac arrest related brain injury are two major causative factors for seizure development in this patient population. With either etiology, seizures area poor prognostic factor. In spite of this, the underlying pathophysiology of seizure development is not well understood. In addition, a standardized treatment regimen with anticonvulsants and outcome assessments following treatment has yet to be established for these post-ischemic seizures. Previous studies have modeled post-ischemic seizures in adult rodents, but similar studies in aging/aged animals, a group that mirrors a higher risk elderly population, remain sparse. Our study therefore aimed to investigate early-onset seizures in aging animals using a hypoxia-ischemia (HI) model. Male C57 black mice18-20-month-old underwent a unilateral occlusion of the common carotid artery followed by a systemic hypoxic episode (8% O2 for 30 min). Early-onset seizures were detected using combined behavioral and electroencephalographic (EEG) monitoring. Brain injury was assessed histologically at different times post HI. Convulsive seizures were observed in 65% of aging mice post-HI but not in control aging mice following either sham surgery or hypoxiaalone. These seizures typically occurred within hours of HI and behaviorally consisted of jumping, fast running, barrel-rolling, and/or falling (loss of the righting reflex) with limb spasms. No evident discharges during any convulsive seizures were seen on cortical-hippocampal EEG recordings. Seizure development was closely associated with acute mortality and severe brain injury on brain histological analysis. Intra-peritoneal injections of lorazepam and fosphenytoin suppressed seizures and improved survival but only when applied prior to seizure onset and not after. These findings together suggest that seizures are a major contributing factor to acute mortality in aging mice following severe brain ischemia and that early anticonvulsive treatment may prevent seizure genesis and improve overall outcomes.
Sherpa Romeo green journal. Open access article. Creative Commons Attribution License applies.
Early-onset seizures , Aging animals , Hypoxia-ischemia , Anticonvulsive treatments , Brain injury
Wang, J., Wu, C., Peng, J., Patel, N., Huang, Y., Gao, X.,...Zhang, L. (2015). Early-onset convulsive seizures induced by brain hypoxia-schemia in aging mice: Effects of anticonvulsive treatments. PLoS ONE, 10(12), e0144113. doi:10.1371/journal.pone.0144113