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

Laboratory investigation

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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.

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.

Article Information

* 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: whutch@uhnres.utoronto.ca.

Please include this information when citing this paper: published online February 15, 2013; DOI: 10.3171/2013.1.JNS121059.

© AANS, except where prohibited by US copyright law.



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    Left: A parasagittal 8-channel microelectrode array was used to record electrical oscillations in the rat cortex. The array was arranged rostrocaudally across the frontoparietal hemicortex with respect to the bregma (mediolateral +3.0 to 3.5, dorsoventral 2.0 mm). Ischemia was induced by coagulating the visible arteriolar branches of the MCA and 1 protruding branch of the ACA using a microcautery pen (denoted by X). Cerebral blood flow was measured with a Doppler flowmeter (arrow). Right: Cerebral blood flow immediately decreased after stroke to 37% of baseline and stayed below baseline for the duration of the experiment (4 rats). Craniotomy and electrode insertion without arteriolar occlusion in sham animals (4 rats) caused no changes in cerebral blood flow.

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    Photomicrograph (A) of deeper layers (V–VI) of the ischemic right sensorimotor cortex. Note the prominent electrolytic lesion of Electrode 4, including point of entry. Cresyl violet, original magnification ×10. Photomicrograph (B) of deeper layers (V–VI) of the ischemic right sensorimotor cortex. The bright green cells are populations of dead and dying (degenerating) neurons. The electrolytic lesion from the tip of Electrode 3 is shown at the top of the image. Fluoro-Jade B, original magnification ×10, bar = 50 μm. Photomicrograph (C) of same area in the contralateral healthy cortex. Only a minimal amount of dead and dying cells are present. Fluoro-Jade B, original magnification ×10, bar = 50 μm.

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    Intracortical microelectrode recording (A) of a TR following ischemia. Note the presence of high-frequency activity immediately preceding the rhythmic spike-wave sequence. The predominant frequency of the epileptiform wave was 5–6 Hz. Illustration (B) of TRs recorded on 4 electrodes at consecutive time points 8 minutes after ischemia. Theta runs appear to spread rostrally from Channel 2 to Channel 1 and caudally to Channels 3 and 4. In 4 of 8 animals, TRs were recorded across contacts. Note that the duration of each TR increased as the ordinal number increased. Channel 1 is the most rostral and Channel 8 the most caudal electrode. Illustration (C) of instance in which the TRs appear to spread only caudally from Channel 4 to Channels 5–7. Theta runs occurred 1 minute after ischemia. Note that the duration of each TR increased as the ordinal number increased. Channel 1 is the most rostral and Channel 8 the most caudal electrode. Illustration (D) of continuous TRs recorded on 2 electrodes (Channels 1 and 4) at 60 minutes after ischemia. The continuous TR was 20 minutes in duration, and this figure illustrates only a 25-second segment. Continuous TRs are smaller in amplitude as compared with the short variant. Fast Fourier transforms waterfall representation (E) of the power spectrum across time of Channel 1 in an ischemic rat. The horizontal axis represents Hz, while the diagonal axis represents time following stroke in minutes (T = 0). Note immediate suppression of power following ischemia. First, transient short TRs start at 10 minutes and reappear with more power at 25 minutes. Continuous TRs with less power than short TRs start at 50 minutes and last for 20 minutes. Ch = channel; uV = microV; s = seconds.

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    Illustration of HFOs preceding the TR (5 runs). All x axes represent seconds, where 0 marks the cessation of the HFO and the onset of the TR. Upper: Trace is an overlay of 5 raw waveforms of TRs recorded at different times on 1 electrode after ischemia. The y axis represents V. Center: Trace is a bandpass filter of the raw waveforms, with 31 Hz as the low end and 175 Hz as the high end. The y axis represents V. Lower: Trace is a 4-Morlet spectrogram of an average of the 5 TRs. Note the increased activity in the high gamma range (80–120 Hz) starting 15 seconds before the TR and terminating at TR onset (0 seconds). The y axis represents Hz.

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    A: Waveform average of 110 PEDs following ischemia. The PED is typically composed of a short negative wave and a high-amplitude positive spike followed by another negative wave. Arrow denotes HFOs. B: Illustrations of low gamma oscillations preceding the PED (26 discharges averaged). All x axes represent seconds, where 0 marks the peak of the positive wave. The upper trace is an overlay of 26 raw waveforms of PEDs recorded at different times on 1 electrode after ischemia. The y axis represents V. The center trace is a bandpass filter of the 26 raw waveforms, with 31 Hz as the low end and 175 Hz as the high end. The y axis represents V. The lower trace is a 4-Morlet spectrogram averaging the 26 PEDs. Illustrated is the increased activity in the low gamma range (30–70 Hz) lasting from 0.1 to 0.08 seconds before the peak of the positive wave. The y axis represents Hz. C: Illustration of PEDs localized to the anterior 4 electrodes (Channels 1–4) 20 minutes after ischemia. Channel 1 is the most rostral and Channel 8 the most caudal electrode.


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