Progress review: hypoglycemic brain damage.
The central question to be addressed in this review can be stated as "How does hypoglycemia kill neurons?" Initial research on hypoglycemic brain damage in the 1930s was aimed at demonstrating the existence of any brain damage whatsoever due to insulin. Recent results indicate that uncomplicated hypoglycemia is capable of killing neurons in the brain. However, the mechanism does not appear to be simply glucose starvation of the neuron resulting in neuronal breakdown. Rather than such an "internal catabolic death" current evidence suggests that in hypoglycemia, neurons are killed from without, i.e. from the extracellular space. Around the time the EEG becomes isoelectric, an endogenous neurotoxin is produced, and is released by the brain into tissue and cerebrospinal fluid. The distribution of necrotic neurons is unlike that in ischemia, being related to white matter and cerebrospinal fluid pathways. The toxin acts by first disrupting dendritic trees, sparing intermediate axons, indicating it to be an excitotoxin. Exact mechanisms of excitotoxic neuronal necrosis are not yet clear, but neuronal death involves hyperexcitation, and culminates in cell membrane rupture. Endogenous excitotoxins produced during hypoglycemia may explain the tendency toward seizure activity often seen clinically. The recent research results on which these findings are based are reviewed, and clinical implications are discussed.
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology; D002421:Caudate Nucleus / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology; D004569:Electroencephalography; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D007003:Hypoglycemia / Q000150:complications / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D007022:Hypotension / Q000150:complications; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D009336:Necrosis; D051381:Rats
D007773:Lactates; D019344:Lactic Acid