title: Modeling early-onset post-ischemic seizures in aging mice.
abstract: Stroke is the leading cause of seizures and epilepsy in the aged population, with post-stroke seizures being a poor prognostic factor. The pathological processes underlying post-stroke seizures are not well understood and studies of these seizures in aging/aged animals remain scarce. Therefore, our primary objective was to model post-stroke seizures in aging mice (C57 black strain, 16-20 months-old), with a focus on early-onset, convulsive seizures that occur within 24-hours of brain ischemia. We utilized a middle cerebral artery occlusion model and examined seizure activity and brain injury using combined behavioral and electroencephalographic monitoring and histological assessments. Aging mice exhibited vigorous convulsive seizures within hours of the middle cerebral artery occlusion. These seizures manifested with jumping, rapid running, barrel-rolling and/or falling all in the absence of hippocampal-cortical electrographic discharges. Seizure development was closely associated with severe brain injury and acute mortality. Anticonvulsive treatments after seizure occurrence offered temporary seizure control but failed to improve animal survival. A separate cohort of adult mice (6-8 months-old) exhibited analogous early-onset convulsive seizures following the middle cerebral artery occlusion but had better survival outcomes following anticonvulsive treatment. Collectively, our data suggest that early-onset convulsive seizures are a result of severe brain ischemia in aging animals.
authors.affiliation: Toronto Western Research Institute, University Health Network, Canada.
authors.forename: Chiping
authors.initials: C
authors.lastname: Wu
authors.affiliation: Toronto Western Research Institute, University Health Network, Canada.
authors.forename: Justin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Toronto Western Research Institute, University Health Network, Canada.
authors.forename: Jessie
authors.initials: J
authors.lastname: Peng
authors.affiliation: Toronto Western Research Institute, University Health Network, Canada.
authors.forename: Nisarg
authors.initials: N
authors.lastname: Patel
authors.affiliation: Toronto Western Research Institute, University Health Network, Canada.
authors.forename: Yayi
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Toronto Western Research Institute, University Health Network, Canada.
authors.forename: Xiaoxing
authors.initials: X
authors.lastname: Gao
authors.affiliation: Toronto Western Research Institute, University Health Network, Canada; Neurology Unit, Department of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Salman
authors.initials: S
authors.lastname: Aljarallah
authors.affiliation: Toronto Western Research Institute, University Health Network, Canada; Department of Surgery (Neurosurgery), University of Toronto, Canada.
authors.forename: James H
authors.initials: JH
authors.lastname: Eubanks
authors.affiliation: Department of Neuroscience, University of Lethbridge, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: McDonald
authors.affiliation: Toronto Western Research Institute, University Health Network, Canada; Department of Medicine (Neurology), University of Toronto, Canada. Electronic address: liangz@uhnres.utoronto.ca.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000375:Aging; D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D016009:Chi-Square Distribution; D004195:Disease Models, Animal; D004564:Electrocoagulation / Q000009:adverse effects; D004569:Electroencephalography; D007839:Functional Laterality; D020244:Infarction, Middle Cerebral Artery / Q000150:complications* / Q000209:etiology; D008140:Lorazepam / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010672:Phenytoin / Q000031:analogs & derivatives / Q000627:therapeutic use; D012640:Seizures / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D013997:Time Factors
chemical_list: D000927:Anticonvulsants; D010672:Phenytoin; C043114:fosphenytoin; D008140:Lorazepam
keywords: Aging; Animal model; Anticonvulsant; Convulsion; EEG; Epilepsy; Ischemia; Mice; Seizures; Stroke