CHANGES IN EXTRACELLULAR AND RAT-BRAIN TISSUE CONCENTRATIONS OF D-BETA-HYDROXYBUTYRATE AFTER 1,3-BUTANEDIOL TREATMENT

1,3-Butanediol (BD) treatment was previously shown to produce a dose-r elated increase of the plasma levels of D-beta-hydroxybutyrate (BHB) a nd to protect brain tissue against hypoxia and ischemia. The purpose o f this study was to test whether BD-induced hyperketonemia was associa ted with changes in brain extracellular and tissue concentrations of B HB. Changes in extracellular levels of BHB were continuously monitored in anesthetized rats before and after intraperitoneal injection of BD (25 mmol/kg), using intracerebral microdialysis coupled to online ana lysis of BHB in the dialysate. Cortical tissue concentrations of BHB w ere determined in control and BD-treated rats (25 and 50 mmol/kg, i.p. ) after freezing of the brain in situ. Butanediol produced a rapid inc rease in dialysate levels of BHB, with a linear relationship between d ialysate and plasma BHB concentrations (r = 0.81, p < 0.001). In contr ast, and although brain tissue levels of BHB were markedly increased a fter BD treatment, they were not related to the plasma concentration o f BHB. Our results suggest that BHB produced from BD did not accumulat e in brain and that BD protects against hypoxia or ischemia by increas ing brain BHB availability.