Delayed treatment with 1,3-butanediol reduces loss of CA1 neurons in the hippocampus of rats following brief forebrain ischemia.
This study examined the effect of 1,3-butanediol on the selective loss of CA1 pyramidal neurons following a short period of near-complete forebrain ischemia. Injection of 55 mmol 1,3-butanediol/kg body weight at 24 h of recirculation and again at 36 h following 10 min of forebrain ischemia markedly reduced damage to CA1 neurons examined at 72 h of recirculation compared with that in saline-treated rats. Comparable treatment with ethanol did not cause significant protection. Neuronal loss was also not reduced by 1,3-butanediol treatment when the ischemic period was extended to 15 min or by single treatments at 24 h or 36 h following 10 min of ischemia. However, a single treatment 5 min after reversal of 10 min of ischemia was effective in ameliorating cell loss. The difference in effectiveness of 1,3-butanediol following 10 min and 15 min of ischemia is consistent with a number of previous studies, indicating that the processes leading to loss of CA1 neurons are modified when the ischemic period is extended. Previous findings that 1,3-butanediol reduced damage in other ischemia-susceptible neuronal subpopulations but not in CA1 neurons most likely reflected the longer period of ischemia which was used. The results of the present investigation demonstrate that administration of 1,3-butanediol offers a novel approach for interfering with post-ischemic loss of CA1 neurons following a brief ischemic period which is effective even when initiated after prolonged recirculation periods.
Department of Medical Biochemistry, Flinders University, Adelaide, Australia.
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Sims
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Heward
D020155:3-Hydroxybutyric Acid; D000090:Acetoacetates / Q000378:metabolism; D000818:Animals; D002545:Brain Ischemia / Q000473:pathology*; D002072:Butylene Glycols / Q000493:pharmacokinetics / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000473:pathology*; D006885:Hydroxybutyrates / Q000378:metabolism; D008297:Male; D016548:Prosencephalon / Q000098:blood supply* / Q000473:pathology; D017966:Pyramidal Cells / Q000187:drug effects*; D051381:Rats
D000090:Acetoacetates; D002072:Butylene Glycols; D006885:Hydroxybutyrates; C028491:1,3-butylene glycol; C016635:acetoacetic acid; D020155:3-Hydroxybutyric Acid