Uncoupling of cerebral glucose supply and utilization after hexane-2,5-dione intoxication in the rat.
Chronic administration of hexane-2,5-dione (2,5-HD) to rats causes an accumulation of neurofilaments within axons that may lead to their degeneration. This occurs in both the CNS and PNS. It has been suggested that one of the effects of 2,5-HD is an impairment of glucose utilization arising from an inhibition of specific glycolytic enzymes. This hypothesis is based principally on evidence obtained in vitro. In the present study, glucose utilization, glucose transport across the blood-brain barrier, and blood flow have been measured in vivo in brain regions of control rats and in three groups of rats treated with 2,5-HD as (a) a single intragastric dose (500 mg/kg of body weight), (b) high chronic doses of 500 mg/kg of body weight for 15 days, or (c) low chronic doses of 250 mg/kg of body weight for 21 days. Group b showed overt signs of neuropathy, whereas groups a and c did not. The results indicate two independent effects of 2,5-HD in the CNS: a dose-dependent inhibition of glucose utilization and an effect on glucose supply and transport across the blood-brain barrier, which is apparent only after chronic treatment.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001812:Blood-Brain Barrier; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D006588:Hexanones / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D007659:Ketones / Q000494:pharmacology*; D008297:Male; D009422:Nervous System Diseases / Q000139:chemically induced; D051381:Rats
D006588:Hexanones; D007659:Ketones; C011269:2,5-hexanedione; D005947:Glucose