Thirty-eight male Wistar rats were exposed to insulin-induced hypoglycemia resulting in periods of cerebral isoelectricity ranging from 10 to 60 min. Plasma glucose levels during cerebral isoelectricity ranged from 0.12 mM to 1.36 mM. Control rats were injected with insulin, but hypoglycemia was terminated with glucose at the stage of large δ-wave EEG slowing. After recovery, the rats were allowed to wake up and survive for 1 wk.
The number of dying neurons was assessed with acid-fuchsin/cresyl-violet-stained, whole-brain, sub-serial sections using direct visual counting of acido-philic, cytoclastic neurons. Brains from control rats that were not allowed to become isoelectric showed no dying neurons. Ten minutes of cerebral isoelectricity produced very minimal brain damage. The density of neuronal necrosis was positively related to the number of minutes of cerebral isoelectricity up to the maximum examined period of 60 min, but showed no correlation with the blood sugar levels.
The cerebral cortex, hippocampus, caudate nucleus, spinal cord, and, to a lesser extent, cerebellar Purkinje cells were affected. The distribution of neuronal necrosis was not identical with that seen in ischemia, but, rather, suggested a CSF-borne neurotoxin operant in contributing to the pathogenesis of neuronal necrosis in hypoglycemie brain damage.
Neuronal death does not occur in hypoglycemia unless the EEG becomes isoelectric, whatever the blood sugar level. Serious brain damage does not occur until electrocerebral silence has been established for at least several minutes. Neuronal death accelerates after 30 min of EEG isoelectricity in the rat. Most animals recovered well after up to 40 min of cerebral isoelectricity.