Abstracts

Severe hypoglycemia constitutes a medical emergency, manifested by seizures, coma and death., Using the isolated intact hippocampus of the immature mouse, we characterized hypoglycemic seizures in vitro during transient hypoglycemia, and their effects on synaptic transmission, neuronal morphology and hippocampal glycogen content., Hypoglycemic seizures occurred less frequently with increasing extracellular glucose concentration. The irreversible loss of synaptic transmission, however, was only dependant on the occurrence of hypoglycemic seizure activity, irrespective of glucose concentration. Comparatively, no hypoglycemic seizures were generated in the isolated neocortical block during transient hypoglycemia, and the loss of synaptic transmission was reversible. Similar spontaneous seizure-like activity in the hippocampus was produced by the glycolysis inhibitor iodoacetate, and 500 [micro]M L-aspartate but not by hypoxia. Hypoglycemic seizure activity was abolished by NMDA and non-NMDA antagonists. The clinical anticonvulsant midazolam, but not phenytoin or valproate also abolished hypoglycemic seizures. In both cases, the prevention of hypoglycemic seizures led to the maintenance of synaptic transmission. Non-glycolytic, oxidative substrates attenuated hypoglycemic seizure activity, without supporting synaptic transmission, even in the presence of adenosine antagonist DPCPX. Methods used to abolish or significantly decrease hypoglycemic seizure activity led to the protection against glycogen depletion and a decrease in cell damage., These data suggest that suppressing neuronal hyperexcitability during hypoglycemia decreases subsequent neuronal damage., (Supported by: The authors would like to acknowledge the support of the Juvenile Diabetes Research Foundation and the Canadian Institutes of Health Research.)