Seizure-like activity in the hypoglycemic rat: Lack of correlation with the electroencephalogram of free-moving animals

SummaryBackgroundThe neuropathology of hypoglycemia and its mechanisms have been well studied. However, the physiopathogenesis of hypoglycemia-related seizures has escaped elucidation. Various animal models reportedly show “seizures” when rendered hypoglycemic, however, correlation with the electroencephalogram (EEG) is inconsistent. In order to characterize the role of the hippocampus and frontal neocortex in the generation of hypoglycemic seizures, this study was undertaken.MethodsAdult rats were implanted stereotaxically with electrodes in the left hippocampus and right frontal cortex. After 1 week, they were fasted 18–24 h, then injected intraperitoneally with insulin, 35 IU/kg. Simultaneous EEG/video monitoring was conducted.ResultsInterpretable EEG recordings were obtained in 8/12 animals. Two showed poor association of seizure-like behaviour (neck extension, vocalizations, tonic extension of the tail, digging or running limb movements) with ictal EEG patterns. Four animals exhibited such behaviours during periods of high amplitude polymorphic slow wave activity, burst-suppression patterns or non-rhythmic spiking. Two others were encephalopathic (behaviourally and electroencephalographically) until death.ConclusionsNot all animals develop seizure-like behaviour when hypoglycemic. If these are seizures, they may originate from subcortical structures, or the “convulsive” behaviours observed may simply be flight/fight reflexes released during profound encephalopathy. Spike activity in the EEG may be a manifestation of this state. Recording EEG from rat cortex and hippocampus during seizure-like activity brought on by hypoglycemia correlates poorly with seizure-like behaviours suggesting that the relevant electrophysiological correlates, if present, are generated from deeper brain structures.