Kumar_2021_Biochem.Biophys.Res.Commun_577_52

Focal ischemia causes irreversible brain damage if cerebral blood flow is not restored promptly. Acute phase excitotoxicity and pro-oxidant and inflammatory events in the sub-chronic phase elicit coagulative necrosis, vascular injury, cerebral oedema, and neurobehavioral deficits. Earlier, in pre-clinical studies arbutin protected behavioral functions and improved therapeutic outcomes in different models of brain and metabolic disorders. Arbutin is natural hydroquinone that might protect against ischemia-reperfusion (I/R) injury. In this study, cerebro-protective effects of arbutin were evaluated in the middle cerebral artery occlusion-reperfusion (MCAo/R) mouse model. Mice were administered arbutin (50, 100 mg/kg, i.p.) for 21 days, and subjected to MCAo/R or sham surgery on day 14. Results showed brain infarction, blood-brain barrier dysfunction, oedema, and neurological deficits 24 h post-MCAo/R injury that were prevented by arbutin. Behavioral evaluations over the sub-chronic phase revealed MCAo/R triggered spatial and working memory deficits. Arbutin protected the memory against MCAo/R injury and decreased hydroxy-2'-deoxyguanosine, protein carbonyls, inflammatory cytokines (tumor necrosis factor-alpha, myeloperoxidase, matrix metalloproteinase-9, inducible nitric oxide synthase), and enhanced glutathione levels in the ischemia ipsilateral hemisphere. Arbutin decreased brain acetylcholinesterase activity, glutamate, and enhanced GABA levels against MCAo/R. Arbutin can alleviate I/R pathogenesis and protects neurobehavioral functions in the MCAo/R mouse model.