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

Simple item page
dc.contributor.authorWang, Justin
dc.contributor.authorWu, Chiping
dc.contributor.authorPeng, Jessie
dc.contributor.authorPatel, Nisarg
dc.contributor.authorHuang, Yayi
dc.contributor.authorGao, Xiaoxing
dc.contributor.authorAljarallah, Salman
dc.contributor.authorEubanks, James H.
dc.contributor.authorMcDonald, Robert J.
dc.contributor.authorZhang, Liang
dc.date.accessioned2019-01-22T23:06:12Z
dc.date.available2019-01-22T23:06:12Z
dc.date.issued2015
dc.descriptionSherpa Romeo green journal. Open access article. Creative Commons Attribution License applies.en_US
dc.description.abstractAging 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.en_US
dc.description.peer-reviewYesen_US
dc.identifier.citationWang, 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.0144113en_US
dc.identifier.urihttps://hdl.handle.net/10133/5269
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.publisher.departmentDepartment of Neuroscienceen_US
dc.publisher.facultyArts and Scienceen_US
dc.publisher.institutionToronto Western Research Instituteen_US
dc.publisher.institutionUniversity of Torontoen_US
dc.publisher.institutionUniversity of Lethbridgeen_US
dc.publisher.institutionKing Saud Universityen_US
dc.publisher.urlhttps://dx.doi.org/10.1371/journal.pone.0144113
dc.subjectEarly-onset seizuresen_US
dc.subjectAging animalsen_US
dc.subjectHypoxia-ischemiaen_US
dc.subjectAnticonvulsive treatmentsen_US
dc.subjectBrain injury
dc.subject.lcshConvulsions
dc.subject.lcshHypoxic-ischemic encephalopathy
dc.subject.lcshAnticonvulsants
dc.subject.lcshMice--Aging
dc.titleEarly-onset convulsive seizures induced by brain hypoxia-ischemia in aging mice: effects of anticonvulsive treatmentsen_US
dc.typeArticleen_US
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
McDonald early onset convulsive.pdf
Size:
13.46 MB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
1.75 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
McDonald, Robert