Effect of beta-hydroxybutyrate, a cerebral function improving agent, on cerebral hypoxia, anoxia and ischemia in mice and rats

Jpn J Pharmacol. 2001 Oct;87(2):143-50. doi: 10.1254/jjp.87.143.


Although improving energy metabolism in ischemic brain has been accepted for the treatment of cerebrovascular diseases, administration of glucose, as an energy substrate, would aggravate ischemic brain damage via activating anaerobic glycolysis, which leads to lactate accumulation. Beta-hydroxybutyrate (BHB) is one of the ketone bodies that can be utilized as an energy source during starvation. The purpose of our study was to define the protective effects of BHB on brain damage induced by hypoxia, anoxia and ischemia. The isotonic solution of BHB administered 30 min before the induction of ischemia at doses over 50 mg x kg(-1) x h(-1) showed remarkable protective effects against hypoxia and anoxia. BHB administered immediately after a bilateral carotid artery ligation at a dose of 30 mg x kg(-1) x h(-1) significantly suppressed the elevation of cerebral water and sodium contents as well as maintaining high ATP and low lactate levels. In contrast, glycerin, a hypertonic agent, substantially reduced the water content but did not show any significant effect on other parameters. We demonstrated that BHB, unlike glycerin, when used as an energy substrate in ischemic brain, has protective effects on cerebral hypoxia, anoxia and ischemia-induced metabolic change.

MeSH terms

  • 3-Hydroxybutyric Acid / administration & dosage
  • 3-Hydroxybutyric Acid / pharmacology*
  • Adenosine Triphosphate / metabolism
  • Animals
  • Blood Pressure / drug effects
  • Body Water / drug effects
  • Brain / blood supply
  • Brain / metabolism
  • Brain / physiopathology*
  • Brain Edema / etiology
  • Brain Edema / physiopathology
  • Brain Ischemia / chemically induced
  • Brain Ischemia / metabolism
  • Brain Ischemia / physiopathology*
  • Cerebrovascular Circulation / drug effects
  • Energy Metabolism / drug effects
  • Glycerol / pharmacology
  • Hypoxia, Brain / chemically induced
  • Hypoxia, Brain / metabolism
  • Hypoxia, Brain / physiopathology*
  • Lactic Acid / metabolism
  • Male
  • Mice
  • Neuroprotective Agents / pharmacology*
  • Nitrogen
  • Potassium Cyanide
  • Rats
  • Rats, Wistar
  • Sodium / metabolism
  • Time Factors


  • Neuroprotective Agents
  • Lactic Acid
  • Adenosine Triphosphate
  • Sodium
  • Potassium Cyanide
  • Nitrogen
  • Glycerol
  • 3-Hydroxybutyric Acid