title: Hypoglycemic and hypoxic modulation of cortical micro-EEG activity in rat brain slices.
abstract: OBJECTIVE
  Electroencephalogram (EEG) recordings exhibit stereotypic alterations during transient ischemia in mammals. One disadvantage of using in vitro models for ischemia studies is the lack of a sensitive electrophysiological measure for the degree of ischemic damage to a large population of neurons. The present study examined effects of hypoglycemia, hypoxia or both on an in vitro micro-EEG model, to determine whether this model provides a sensitive measure.
  
  
  METHODS
  Theta frequency (4-8 Hz) micro-EEG oscillations were evoked in rat neocortical brain slices using the cholinergic agonist carbachol (100 microM) and the GABA(A) antagonist bicuculline (10 microM). Extracellular field micro-EEG signals and whole cell patch clamp recordings were used to monitor electrical activity.
  
  
  RESULTS
  Upon removal of oxygen and/or glucose, theta oscillation amplitudes progressively declined to isoelectric levels. Low frequency delta oscillations (0.5-3.0 Hz) and burst suppression discharges were prominent during hypoglycemic episodes and upon recovery. Time to onset of isoelectric activity was faster in slices deprived of both glucose and oxygen (7.0 +/- 1.8 min) 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 control levels (87.7 +/- 16.9% control amplitude, P > 0.35 (t test compared with control) for hypoglycemia; 93.6 +/- 27.0%, P > 0.72 for hypoxia). Spreading 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, but 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 that synchronized micro-EEG activity may be a useful and sensitive indicator of early-onset and possibly reversible ischemic damage.
authors.affiliation: Department of Anesthesia, Stanford University School of Medicine, CA 94305-5117, USA.
authors.forename: G D
authors.initials: GD
authors.lastname: Rabinovici
authors.forename: H S
authors.initials: HS
authors.lastname: Lukatch
authors.forename: M B
authors.initials: MB
authors.lastname: MacIver
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D004558:Electric Stimulation; D004569:Electroencephalography / Q000187:drug effects / Q000379:methods*; D058787:GABA-A Receptor Antagonists; D007003:Hypoglycemia / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D002546:Ischemic Attack, Transient / Q000503:physiopathology; D008297:Male; D008839:Microelectrodes; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity
chemical_list: D058787:GABA-A Receptor Antagonists; D002217:Carbachol; D001640:Bicuculline