Electrocorticographic evidence of deteriorating penumbral conditions associated with delayed peri-infarct depolarizations following reperfusion in rat focal cerebral ischemia

Abstract

Changes in electroencephalographic (EEG) activity following focal cerebral ischemia include focal slowing, voltage attenuation, and the waxing and waning of stereotyped activities including PLEDs, seizures, and interictal discharges. However, spreading depolarizations (SD), in the form of cortical spreading depression or peri-infarct depolarizations, are the dominant electrophysiologic events after middle cerebral artery occlusion (MCAo), occurring not only during ischemia but also in a 'secondary phase' throughout the period of infarct maturation 8–24 h post-ischemia. Here we study manifestations of SDs in electrocorticographic (ECoG) patterns to investigate ECoG diagnostics of depolarization events and characterize effects of secondary phase, post-reperfusion depolarizations. Monopolar ECoG signals were recorded continuously from epidural, non-polarizable electrodes during 2 h of MCAo and 22 h reperfusion in freely behaving rats. Recordings were made frontal and parietal electrodes adjacent to the presumed 'penumbra'. Signals were amplified for recording of DC potential and traditional AC-coupled ECoG (0.5–50 Hz band pass). During 2 h MCAo, ECoG amplitude was suppressed relative to baseline. Brief (mean: 72 sec) seizures and SDs (mean: 14 events) recurred frequently but without temporal relationship to each other. During SD, ECoG amplitude remained constant, indicating penumbral conditions (Figure 1, top). Following reperfusion, seizures and SDs ceased, ECoG amplitude recovered, and over the next several hours pathologic delta waves (polymorphic delta activity and PLEDs) dominated the ECoG with progressively increasing amplitude. After a variable period (4–12 h), the ECoG amplitude decreased dramatically in association with the onset of a prolonged repetitive series of depolarizations (mean: 58 events). Initial depolarizations in this phase produced transient depressions of the high amplitude ECoG signal (Figure 1, middle). After several repetitive depolarizations, however, the ECoG became permanently depressed, with no further transient depressions during subsequent depolarizations (Figure 1, bottom). These results were confirmed with bipolar ECoG recordings from penumbral regions. Finally we show that depolarizations could be detected in baseline shifts of the AC-ECoG signal with a low (0.03 Hz) high-pass cutoff setting. Baseline shifts signalled the derivative of the DC potential. The progressive decrement and then permanent depression of the ECoG caused by secondary phase SDs evidences deleterious effects of post-reperfusion depolarizations, and likely the progressive recruitment of penumbral and/or core-infarcted tissue. Furthermore, the lack of transient ECoG depression during SD in this period demonstrates penumbral conditions and suggests that depolarizations can be manifested as 'peri-infarct depolarizations' even following reperfusion.