Protective action of 1,3-butanediol in cerebral ischemia. A neurologic, histologic, and metabolic study.
1,3-Butanediol (BD) is converted in the body to beta-hydroxybutyrate, and previous studies have shown that hyperketonemia had beneficial effects in experimental models of generalized hypoxia. The aim of this study was to determine if BD would reduce brain damage following cerebral ischemia. A transient forebrain ischemia of 30-min duration was induced by the four-vessel occlusion technique in control and BD-treated rats (25 mmol/kg, i.p.; 30 min prior to ischemia). BD treatment led to significant improvement of neurologic deficit during the 72-h recovery period and reduced neuronal damage in the striatum and cortex but not in the CA1 sector of the hippocampus. Evaluation of cerebral energy metabolism before and at the end of the ischemic period showed that the treatment did not change the preischemic glycolytic and energy metabolite levels but attenuated the ischemia-induced metabolic alterations. It increased energy charge, phosphocreatine, and glucose levels, and reduced lactate accumulation. The decrease in brain lactate concentration might account for the beneficial effects of BD by minimizing the neuropathological consequences of lactic acidosis.
Laboratoire de Pharmacodynamie et Physiologie Pharmaceutique, Faculté de Pharmacie, Université de Dijon, France.
C
C
Marie
A M
AM
Bralet
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J
Bralet
D020155:3-Hydroxybutyric Acid; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002072:Butylene Glycols / Q000494:pharmacology* / Q000627:therapeutic use; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology; D004734:Energy Metabolism; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D006885:Hydroxybutyrates / Q000097:blood; D002546:Ischemic Attack, Transient / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D051381:Rats
D001786:Blood Glucose; D002072:Butylene Glycols; D006885:Hydroxybutyrates; C028491:1,3-butylene glycol; D020155:3-Hydroxybutyric Acid