Hypoglycemic and hypoxic modulation of cortical micro-EEG activity in rat brain slices

Objective: Electroencephalogram (EEG) recordings exhibit stereotypic altera tions during transient ischemia in mammals. One disadvantage of using in vi tro models for ischemia studies is the lack of a sensitive electrophysiolog ical measure for the degree of ischemic damage to a large population of neu rons. The present study examined effects of hypoglycemia, hypoxia or both o n an in vitro micro-EEG model, to determine whether this model provides a s ensitive measure. Methods: Theta frequency (4-8 Hz) micro-EEG oscillations were evoked in rat neocortical brain slices using the cholinergic agonist carbachol (100 mu M ) and the GABA(A) antagonist bicuculline (10 mu M). Extracellular field mic ro-EEG signals and whole cell patch clamp recordings were used to monitor e lectrical activity. Results: Upon removal of oxygen and/or glucose, theta oscillation amplitude s progressively declined to isoelectric levels. Low frequency delta oscilla tions (0.5-3.0 Hz) and burst suppression discharges were prominent during h ypoglycemic episodes and upon recovery. Time to onset of isoelectric activi ty was faster in slices deprived of both glucose and oxygen (7.0 +/- 1.8 mi n) and oxygen alone (5.0 +/- 1.5 min) compared to hypoglycemia alone (25.6 +/- 3.8 min, P < 0.01, ANOVA). Hypoxia and hypoglycemia-induced isoelectric activity occurred prior to significant population spike depression from co ntrol levels (87.7 +/- 16.9% control amplitude, P > 0.35 (t test compared w ith control) for hypoglycemia; 93.6 +/- 27.0%, P > 0.72 for hypoxia). Sprea ding depression (SD) was observed in 11/12 (91.7%) slices deprived of both sugar and oxygen, but not in hypoxic (0/4) or hypoglycemic (0/5) slices. in all cases, SD occurred later than isoelectric activity. Theta oscillations recovered within 10 min in 12/13 (92.3%) slices that did not undergo SD, b ut slices that underwent SD failed to recover theta activity (0/4), though all (4/4) at least partially recovered the population spike (>40%). Conclusions: These results suggest chat synchronized micro-EEG activity may be a useful and sensitive indicator of early-onset and possibly reversible ischemic damage. (C) 2000 Elsevier Science Ireland Ltd. All rights reserve d.