Beta-hydroxybutyrate, a cerebral function improving agent, protects rat brain against ischemic damage caused by permanent and transient focal cerebral ischemia.
In our previous study, beta-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 x kg(-1) x 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.
Suzuki
Motohisa
M
Shimizu Research Laboratories, Shimizu Pharmaceutical Co, Ltd, Shizuoka, Japan. motohisa-s@shimizu-pharm.co.jp
Suzuki
Mayumi
M
Kitamura
Yukika
Y
Mori
Saori
S
Sato
Kazunori
K
Dohi
Sekiko
S
Sato
Takashi
T
Matsuura
Akihiro
A
Hiraide
Atsushi
A
D020155:3-Hydroxybutyric Acid / Q000494:pharmacology*; D000818:Animals; D002545:Brain Ischemia / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002540:Cerebral Cortex / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D007262:Infusions, Intravenous; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D008297:Male; D020768:Middle Cerebral Artery; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function
D018696:Neuroprotective Agents; D020155:3-Hydroxybutyric Acid