7,8-dihydroxyflavone, a small-molecule tropomyosin-related kinase B (TrkB) agonist, attenuates cerebral ischemia and reperfusion injury in rats

• Published in: Journal of molecular histology 2014-04, Vol.45 (2), p.129-140
• Main Authors: Wang, Bing, Wu, Nan, Liang, Feng, Zhang, Shuqin, Ni, Weimin, Cao, Yunxing, Xia, Dongjian, Xi, Huanjiu
• Format: Article
• Language: English
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Cell Biology; Developmental Biology; Drug Evaluation, Preclinical; Enzyme Activation; Enzyme Activators - pharmacology; Enzyme Activators - therapeutic use; Flavones - pharmacology; Flavones - therapeutic use; Glutathione - metabolism; Glutathione Peroxidase - metabolism; Infarction, Middle Cerebral Artery - drug therapy; Life Sciences; Male; Malondialdehyde - metabolism; Nitric Oxide - metabolism; Original Paper; Oxidative Stress; Rats; Rats, Sprague-Dawley; Receptor, trkB - agonists; Receptor, trkB - metabolism; Reperfusion Injury - prevention & control; Superoxide Dismutase - metabolism
• ISSN: 1567-2379; 1567-2387
• DOI: 10.1007/s10735-013-9539-y

7,8-dihydroxyflavone (7,8-DHF) is a recently identified potent agonist of tropomyosin-related kinase B that can cross the blood–brain barrier after oral or intraperitoneal administration. The aim of the present study was to determine whether 7,8-DHF has neuroprotective effects against cerebral ischemia and reperfusion (I/R) injury and, if so, to investigate the possible underlying mechanisms. Cerebral I/R injury rats were induced by middle cerebral artery occlusion for 90 min followed by reperfusion for 24 h. 7,8-DHF was administered intraperitoneally at a dose of 5 mg/kg immediately after ischemia. Our results showed that 7,8-DHF significantly reduced neurological deficit scores, infarct volumes, and neuronal apoptosis in brains of I/R rats. Meanwhile, 7,8-DHF also increased Bcl-2 expression, decreased expression of cleaved caspase-3, Bax and inducible nitric oxide synthase, and inhibited nuclear factor-κB activation in ischemic cortex. Finally, malondialdehyde and nitric oxide contents were reduced, but activities of glutathione, glutathione peroxidase and superoxide dismutase were restored in ischemic cortex treated with 7,8-DHF. Taken together, our findings demonstrated that 7,8-DHF is able to protect against cerebral I/R injury, which may be, at least in part, attributable to its anti-apoptotic, anti-oxidative and anti-inflammatory actions.