The postischemic brain has greater susceptibility to epileptogenic activity than physiologically healthy tissue. Epileptiform discharges are thought to exacerbate postischemic brain function. The aim of this study was to develop an in vivo focal stroke model in rats to characterize epileptiform activity.
The authors developed a parasagittal 8-channel intracortical microelectrode array to obtain recordings of cortical oscillations of local field potentials following partial middle and anterior cerebral artery occlusion. All experiments were done in urethane-anesthetized Sprague-Dawley rats.
Theta runs (TRs), ranging in duration from 5 seconds to 5 minutes, were observed in 62% of animals within 1 hour of occlusion. High-frequency oscillations (HFOs) in the high gamma range (80–120 Hz) were observed 5–15 seconds before each TR and terminated at the onset of the discharge. Periodic epileptiform discharges (PEDs) were detected in 54% of rats following ischemia. The PEDs consisted of an early negative slow wave, a high-amplitude positive spike, and a short negative slow wave. Transient HFOs in the low gamma range (30–70 Hz) occurred during the first negative wave and the rising phase of the positive spike of the PED.
These recordings provide the first intracortical evidence of a high-frequency component that could be an important element for diagnosis and intervention in postischemic epileptogenic activity. The early onset also suggests that HFOs could serve as a reliable method of detecting small epileptiform events and could be used as a consideration in deciding whether antiepileptic medications are appropriate as part of a patient's poststroke care.
* Drs. Aarts and Hutchison share senior authorship of this work.
Address correspondence to: William D. Hutchison, Ph.D., University of Toronto, Toronto Western Research Institute, 399 Bathurst Street, MP11-308, Toronto, Ontario, Canada M5T 2S8. email: email@example.com.
Please include this information when citing this paper: published online February 15, 2013; DOI: 10.3171/2013.1.JNS121059.
BraginAEngelJJrWilsonCLFriedIMathernGW: Hippocampal and entorhinal cortex high-frequency oscillations (100–500 Hz) in human epileptic brain and in kainic acid— treated rats with chronic seizures. Epilepsia40:127–1371999
ChatrianGEShawCMLeffmanH: The significance of periodic lateralized epileptiform discharges in EEG: an electrographic, clinical and pathological study. Electroencephalogr Clin Neurophysiol17:177–1931964
JacobsJLeVanPChanderRHallJDubeauFGotmanJ: Interictal high-frequency oscillations (80-500 Hz) are an indicator of seizure onset areas independent of spikes in the human epileptic brain. Epilepsia49:1893–19072008
KellyKMJukkolaPIKharlamovEADowneyKLMcBrideJWStrongR: Long-term video-EEG recordings following transient unilateral middle cerebral and common carotid artery occlusion in Long-Evans rats. Exp Neurol201:495–5062006
van TuijlJHvan RaakEPde KromMCLodderJAldenkampAP: Early treatment after stroke for the prevention of late epileptic seizures: a report on the problems performing a randomised placebo-controlled double-blind trial aimed at anti-epileptogenesis. Seizure20:285–2912011
VelísekLVelískováJChudomelOPoonKLRobesonKMarshallB: Metabolic environment in substantia nigra reticulata is critical for the expression and control of hypoglycemia-induced seizures. J Neurosci28:9349–93622008
WilliamsAJBautistaCCChenRWDaveJRLuXCTortellaFC: Evaluation of gabapentin and ethosuximide for treatment of acute nonconvulsive seizures following ischemic brain injury in rats. J Pharmacol Exp Ther318:947–9552006