β-Hydroxybutyrate, a Cerebral Function Improving Agent, Protects Rat Brain Against Ischemic Damage Caused by Permanent and Transient Focal Cerebral Ischemia

Motohisa Suzuki; Mayumi Suzuki; Yukika Kitamura; Saori Mori; Kazunori Sato; Sekiko Dohi; Takashi Sato; Akihiro Matsuura; Atsushi Hiraide

doi:10.1254/jjp.89.36

Full Papers

β-Hydroxybutyrate, a Cerebral Function Improving Agent, Protects Rat Brain Against Ischemic Damage Caused by Permanent and Transient Focal Cerebral Ischemia

Motohisa Suzuki, Mayumi Suzuki, Yukika Kitamura, Saori Mori, Kazunori Sato, Sekiko Dohi, Takashi Sato, Akihiro Matsuura, Atsushi Hiraide

Author information

Motohisa Suzuki
Shimizu Research Laboratories, Research and Development Division, Shimizu Pharmaceutical Co., Ltd.
Mayumi Suzuki
Shimizu Research Laboratories, Research and Development Division, Shimizu Pharmaceutical Co., Ltd.
Yukika Kitamura
Shimizu Research Laboratories, Research and Development Division, Shimizu Pharmaceutical Co., Ltd.
Saori Mori
Shimizu Research Laboratories, Research and Development Division, Shimizu Pharmaceutical Co., Ltd.
Kazunori Sato
Shimizu Research Laboratories, Research and Development Division, Shimizu Pharmaceutical Co., Ltd.
Sekiko Dohi
Shimizu Research Laboratories, Research and Development Division, Shimizu Pharmaceutical Co., Ltd.
Takashi Sato
Shimizu Research Laboratories, Research and Development Division, Shimizu Pharmaceutical Co., Ltd.
Akihiro Matsuura
Shimizu Research Laboratories, Research and Development Division, Shimizu Pharmaceutical Co., Ltd.
Atsushi Hiraide
Department of General Medicine, Osaka University Medical School

Keywords: β-Hydroxybutyrate, Permanent ischemia, Transient ischemia, Middle cerebral artery occlusion, Cerebroprotection

JOURNAL FREE ACCESS

2002 Volume 89 Issue 1 Pages 36-43

DOI https://doi.org/10.1254/jjp.89.36

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Abstract

In our previous study, β-hydroxybutyrate (BHB) was found to prolong survival time and to inhibit cerebral edema by improving energy metabolism in the hypoxia, anoxia and global cerebral ischemia models. In this study, the cerebroprotective effect of BHB was examined in rats with permanent (p)-occlusion and transient (t)-occlusion of middle cerebral artery (MCA). BHB (30 mg · kg⁻¹ · h⁻¹) was continuously administered through the femoral vein. In rats with p-MCA occlusion, BHB significantly reduced infarct area at 24 h after the occlusion, but not at 72 h after the occlusion. In rats with 2-h t-MCA occlusion followed by 22-h reperfusion, BHB significantly reduced cerebral infarct area, edema formation, lipid peroxidation and neurological deficits. Moreover, in the t-MCA occlusion model, delayed administration of BHB started at 1 h after the initiation of the MCA occlusion also significantly reduced cerebral infarct area. Taking together the results obtained in our previous study into account, these results indicate that BHB decreased cerebral edema formation and infarct area by improving of the cerebral energy metabolism during ischemia and by inhibition of lipid peroxidation after reperfusion.

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