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

The Japanese Journal of Pharmacology

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

[1] Shimizu Research Center, Research and Development Division, Shimizu Pharmaceutical Co., Ltd.;Department of General Medicine, Osaka University Medical School

关键词: β-Hydroxybutyrate;    Glycerin;    Anti-anoxic effect;    Cerebral ischemia;    Cerebral energy metabolism;   

DOI  :  10.1254/jjp.87.143

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(31)Cited-By(51)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. β-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 · k g −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.

【 授权许可】

Unknown