Tanveer Singh1, Suchitra Joshi1, John M Williamson1, Jaideep Kapur1,2,3. 1. Department of Neurology, University of Virginia, Charlottesville, VA, USA. 2. UVA Brain Institute, University of Virginia, Charlottesville, VA, USA. 3. Department of Neuroscience, University of Virginia, Charlottesville, VA, USA.
Abstract
OBJECTIVE: To characterize neocortical onset status epilepticus (SE) in the C57BL/6J mouse. METHODS: We induced SE by administering homocysteine 16-18 hours after cobalt (Co) implantation. SE was monitored by video and electroencephalography (EEG). We evaluated brain structure with magnetic resonance imaging (MRI). Neurodegeneration was evaluated 72 hours after SE using Fluoro-Jade C staining. RESULTS: Cobalt triggered seizures in a dose-dependent manner (median effective dose, ED50 = 0.78 mg) and the latency to peak seizure frequency shortened with increased dose. Animals developed SE after homocysteine administration. SE began with early intermittent focal seizures, consisting of frontal onset rhythmic spike-wave discharges manifested as focal dystonia with clonus. These focal seizures then evolved into generalized continuous convulsive activity. Behavioral manifestations of SE included tonic stiffening, bilateral limb clonus, and bilateral tonic-clonic movements, which were accompanied by generalized rhythmic spike-wave discharges on EEG. After prolonged seizures, animals became comatose with intermittent bilateral myoclonic seizures or jerks. During this period, EEG showed seizures interspersed with generalized periodic discharges on a suppressed background. MRI obtained when animals were in a coma revealed edema, midline shift in frontal lobe around the Co implantation site, and ventricular effacement. Fluoro-Jade C staining revealed neurodegeneration in the cortex, amygdala, and thalamus. SIGNIFICANCE: We have developed a mouse model of severe, refractory cortical-onset SE, consisting of convulsions merging into a coma, EEG patterns of cortical seizures, and injury, with evidence of widespread neocortical edema and damage. This model replicates many features of acute seizures and SE resulting from traumatic brain injury, subarachnoid, and lobar hemorrhage.
OBJECTIVE: To characterize neocortical onset status epilepticus (SE) in the C57BL/6J mouse. METHODS: We induced SE by administering homocysteine 16-18 hours after cobalt (Co) implantation. SE was monitored by video and electroencephalography (EEG). We evaluated brain structure with magnetic resonance imaging (MRI). Neurodegeneration was evaluated 72 hours after SE using Fluoro-Jade C staining. RESULTS: Cobalt triggered seizures in a dose-dependent manner (median effective dose, ED50 = 0.78 mg) and the latency to peak seizure frequency shortened with increased dose. Animals developed SE after homocysteine administration. SE began with early intermittent focal seizures, consisting of frontal onset rhythmic spike-wave discharges manifested as focal dystonia with clonus. These focal seizures then evolved into generalized continuous convulsive activity. Behavioral manifestations of SE included tonic stiffening, bilateral limb clonus, and bilateral tonic-clonic movements, which were accompanied by generalized rhythmic spike-wave discharges on EEG. After prolonged seizures, animals became comatose with intermittent bilateral myoclonic seizures or jerks. During this period, EEG showed seizures interspersed with generalized periodic discharges on a suppressed background. MRI obtained when animals were in a coma revealed edema, midline shift in frontal lobe around the Co implantation site, and ventricular effacement. Fluoro-Jade C staining revealed neurodegeneration in the cortex, amygdala, and thalamus. SIGNIFICANCE: We have developed a mouse model of severe, refractory cortical-onset SE, consisting of convulsions merging into a coma, EEG patterns of cortical seizures, and injury, with evidence of widespread neocortical edema and damage. This model replicates many features of acute seizures and SE resulting from traumatic brain injury, subarachnoid, and lobar hemorrhage.
Authors: Jay Gavvala; Nicholas Abend; Suzette LaRoche; Cecil Hahn; Susan T Herman; Jan Claassen; Mícheál Macken; Stephan Schuele; Elizabeth Gerard Journal: Epilepsia Date: 2014-09-29 Impact factor: 5.864
Authors: A Rasic-Markovic; D Hrncic; D Krstic; M Colovic; E Djuric; B Rankov-Petrovic; V Susic; O Stanojlovic; D Djuric Journal: Can J Physiol Pharmacol Date: 2016-06-22 Impact factor: 2.273
Authors: Eugen Trinka; Hannah Cock; Dale Hesdorffer; Andrea O Rossetti; Ingrid E Scheffer; Shlomo Shinnar; Simon Shorvon; Daniel H Lowenstein Journal: Epilepsia Date: 2015-09-04 Impact factor: 5.864