title: Posttraumatic seizures and epilepsy in adult rats after controlled cortical impact.
abstract: Posttraumatic epilepsy (PTE) has been modeled with different techniques of experimental traumatic brain injury (TBI) using mice and rats at various ages. We hypothesized that the technique of controlled cortical impact (CCI) could be used to establish a model of PTE in young adult rats. A total of 156 male Sprague-Dawley rats of 2-3 months of age (128 CCI-injured and 28 controls) was used for monitoring and/or anatomical studies. Provoked class 3-5 seizures were recorded by video monitoring in 7/57 (12.3%) animals in the week immediately following CCI of the right parietal cortex; none of the 7 animals demonstrated subsequent spontaneous convulsive seizures. Monitoring with video and/or video-EEG was performed on 128 animals at various time points 8-619 days beyond one week following CCI during which 26 (20.3%) demonstrated nonconvulsive or convulsive epileptic seizures. Nonconvulsive epileptic seizures of >10s were demonstrated in 7/40 (17.5%) animals implanted with 2 or 3 depth electrodes and usually characterized by an initial change in behavior (head raising or animal alerting) followed by motor arrest during an ictal discharge that consisted of high-amplitude spikes or spike-waves with frequencies ranging between 1 and 2Hz class 3-5 epileptic seizures were recorded by video monitoring in 17/88 (19%) and by video-EEG in 2/40 (5%) CCI-injured animals. Ninety of 156 (58%) animals (79 CCI-injured, 13 controls) underwent transcardial perfusion for gross and microscopic studies. CCI caused severe brain tissue loss and cavitation of the ipsilateral cerebral hemisphere associated with cell loss in the hippocampal CA1 and CA3 regions, hilus, and dentate granule cells, and thalamus. All Timm-stained CCI-injured brains demonstrated ipsilateral hippocampal mossy fiber sprouting in the inner molecular layer. These results indicate that the CCI model of TBI in adult rats can be used to study the structure-function relationships that underlie epileptogenesis and PTE.
authors.affiliation: Center for Neuroscience Research, Allegheny Health Network Research Institute, Pittsburgh, PA, United States; Department of Neurology, Allegheny General Hospital, Pittsburgh, PA, United States; Department of Neurology, Philadelphia, PA, United States; Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, United States. Electronic address: kelly@wpahs.org.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Kelly
authors.affiliation: Center for Neuroscience Research, Allegheny Health Network Research Institute, Pittsburgh, PA, United States. Electronic address: emiller@wpahs.org.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Miller
authors.affiliation: Ilia State University, Faculty of Natural Sciences and Engineering, Tbilisi, Georgia. Electronic address: eka_lepsveridze@iliauni.edu.ge.
authors.forename: Eka
authors.initials: E
authors.lastname: Lepsveridze
authors.affiliation: Center for Neuroscience Research, Allegheny Health Network Research Institute, Pittsburgh, PA, United States; Department of Neurology, Allegheny General Hospital, Pittsburgh, PA, United States; Department of Neurology, Philadelphia, PA, United States.
authors.forename: Elena A
authors.initials: EA
authors.lastname: Kharlamov
authors.affiliation: Center for Neuroscience Research, Allegheny Health Network Research Institute, Pittsburgh, PA, United States; Department of Neurology, Allegheny General Hospital, Pittsburgh, PA, United States; Department of Neurology, Philadelphia, PA, United States. Electronic address: zmchedlishvili@sentientmedical.com.
authors.forename: Zakaria
authors.initials: Z
authors.lastname: Mchedlishvili
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000150:complications / Q000503:physiopathology*; D004569:Electroencephalography; D004834:Epilepsy, Post-Traumatic / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D019599:Mossy Fibers, Hippocampal / Q000503:physiopathology*; D010296:Parietal Lobe / Q000293:injuries* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000209:etiology / Q000503:physiopathology*
keywords: Mossy fiber sprouting; Traumatic brain injury; Video-EEG monitoring