High-frequency cortical activity associated with postischemic epileptiform discharges in an in vivo rat focal stroke model

Laboratory investigation

Luka R. Srejic M.Sc.1, Taufik A. Valiante M.D., Ph.D., F.R.C.S.3, Michelle M. Aarts Ph.D.1,4, and William D. Hutchison Ph.D.2,3
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  • 1 Institute of Medical Sciences and
  • | 2 Department of Physiology, University of Toronto;
  • | 3 Division of Neurosurgery, Department of Surgery, Toronto Western Research Institute and Krembil Neuroscience Centre; and
  • | 4 Department of Biological Sciences, University of Toronto at Scarborough, Toronto, Ontario, Canada
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Object

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.

Methods

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.

Results

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.

Conclusions

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.

Abbreviations used in this paper:

ACA = anterior cerebral artery; EEG = electroencephalography; GABA = γ-aminobutyric acid; HFO = high-frequency oscillation; MCAO = middle cerebral artery occlusion; PED = periodic epileptiform discharge; TR = theta run.

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