Jpn. J. Pharmacol. 87 (2), 143-150 (2001)

Effect of b-Hydroxybutyrate, a Cerebral Function Improving Agent, on Cerebral Hypoxia, Anoxia and Ischemia in Mice and Rats

Motohisa Suzuki1,*, Mayumi Suzuki1, Kazunori Sato1, Sekiko Dohi1, Takashi Sato1, Akihiro Matsuura1 and Atsushi Hiraide2

1Shimizu Research Center, Research and Development Division, Shimizu Pharmaceutical Co., Ltd., 649-1, Miyakami, Shimizu, Shizuoka 424-0911, Japan
2Department of General Medicine, Osaka University Medical School, 2-15, Yamadaoka, Suita, Osaka 565-0871, Japan

*Corresponding author. FAX: +81-543-35-4858, E-mail:

Abstract: 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. b-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 · kg-1 · 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 · kg-1 · 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.

Keywords: b-Hydroxybutyrate, Glycerin, Anti-anoxic effect, Cerebral ischemia, Cerebral energy metabolism

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