Hydroxycarboxylic Acid Receptor 1 and Neuroprotection in a Mouse Model of Cerebral Ischemia-Reperfusion

Lactate is an intriguing molecule with emerging physiological roles in the brain. It has beneficial effects animal models of acute brain injuries and traumatic injury or subarachnoid hemorrhage patients. However, mechanism by which lactate provides protection unclear. While there evidence a metabolic effect providing energy to deprived neurons, it can also activate hydroxycarboxylic acid receptor 1 (HCAR1), Gi-coupled protein that modulates neuronal firing rates. After cerebral hypoxia-ischemia, endogenously produced largely increased, exogenous administration more decrease lesion size ameliorate neurological outcome. To test whether HCAR1 plays role lactate-induced neuroprotection, we injected agonists 3-chloro-5-hydroxybenzoic 3,5-dihydroxybenzoic into mice subjected 30-min middle artery occlusion. The vivo at reperfusion did not appear exert any relevant protective as seen administration. Our results suggest after hypoxia-ischemia come rather from than its signaling through HCAR1.