Beneficial effect of 1,3-butanediol on cerebral energy metabolism and edema following brain embolization in rats.
We assessed the effect of 1,3-butanediol on cerebral energy metabolism and edema after inducing multifocal brain infarcts in 108 rats by the intracarotid injection of 50-microns carbonized microspheres. An ethanol dimer that induces systemic ketosis, 25 mmol/kg i.p. butanediol was injected every 3 hours to produce a sustained increase in the plasma level of beta-hydroxybutyrate. Treatment significantly attenuated ischemia-induced metabolic changes by increasing the concentrations of phosphocreatine, adenosine triphosphate, and glycogen and by reducing the concentrations of pyruvate and lactate. Lactate concentration 2, 6, and 12 hours after embolization decreased by 13%, 44%, and 46%, respectively. Brain water content increased from 78.63% in six unembolized rats to 80.93% in 12 saline-treated and 79.57% in seven butanediol-treated rats 12 hours after embolization. (p less than 0.05). The decrease in water content was associated with significant decreases in the concentrations of sodium and chloride. The antiedema effect of butanediol could not be explained by an osmotic mechanism since equimolar doses of urea or ethanol were ineffective. Our results support the hypothesis that the beneficial effect of butanediol is mediated through cerebral utilization of ketone bodies arising from butanediol metabolism, reducing the rate of glycolysis and the deleterious accumulation of lactic acid during ischemia.
Gueldry
S
S
Laboratoire de Pharmacodynamie et Physiologie Pharmaceutique, Faculté de Pharmacie, Dijon, France.
Marie
C
C
Rochette
L
L
Bralet
J
J
D020155:3-Hydroxybutyric Acid; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001834:Body Water / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001929:Brain Edema / Q000097:blood / Q000378:metabolism*; D002072:Butylene Glycols / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology; D006885:Hydroxybutyrates / Q000097:blood; D002542:Intracranial Embolism and Thrombosis / Q000097:blood / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D014508:Urea / Q000494:pharmacology
D001786:Blood Glucose; D002072:Butylene Glycols; D006885:Hydroxybutyrates; D000431:Ethanol; C028491:1,3-butylene glycol; D014508:Urea; D020155:3-Hydroxybutyric Acid