Hydroxybutyrate promotes the recovery from cerebral infarction by activating Amp-activated protein kinase signaling.

Recent studies have shown that hydroxybutyrate (GHB) is effective for protection against ischemia/brain damage in rat models. However, the specific underlying mechanism is poorly understood. In line with the previous studies, the present data showed that GHB improves cerebral blood flow (CBF) and physiological variables, including pH, pCO and pO. Using CD31-immunofluorescence staining, a reduction of blood vessel density was indicated in the middle cerebral artery occlusion (MCAO) group; however, GHB treatment enhanced the cerebral vascular density in the ischemic area. In addition, GHB treatment increased the number of BrdU/lectin double-positive cells. Furthermore, the reduction of nestin-positive cells was identified in the brain of MCAO rats, while the number of nestin-positive cells was significantly increased after GHB administration. Compared with the sham group, the activation of Amp-activated protein kinase (AMPK) was identified in MCAO rats, suggesting stress-mediated AMPK activation after ischemia. Furthermore, the western blot assay showed that GHB treatment resulted in further activation of AMPK and endothelial nitric oxide synthase (eNOS), suggesting an enhanced energy supply. In summary, the present novel data indicates that GHB promotes the recovery from cerebral infarction mainly by activating AMPK and eNOS signaling, thereby enhancing angiogenesis and neuron regeneration.