title: 7,8-dihydroxyflavone, a small-molecule tropomyosin-related kinase B (TrkB) agonist, attenuates cerebral ischemia and reperfusion injury in rats.
abstract: 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.
authors.affiliation: Department of Human Anatomy, Histology and Embryology, China Medical University, 92 Bei'er Road, Shenyang, 110001, Liaoning, People's Republic of China.
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.forename: Nan
authors.initials: N
authors.lastname: Wu
authors.forename: Feng
authors.initials: F
authors.lastname: Liang
authors.forename: Shuqin
authors.initials: S
authors.lastname: Zhang
authors.forename: Weimin
authors.initials: W
authors.lastname: Ni
authors.forename: Yunxing
authors.initials: Y
authors.lastname: Cao
authors.forename: Dongjian
authors.initials: D
authors.lastname: Xia
authors.forename: Huanjiu
authors.initials: H
authors.lastname: Xi
mesh_terms: D000818:Animals; D004353:Drug Evaluation, Preclinical; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000494:pharmacology* / Q000627:therapeutic use; D047309:Flavones / Q000494:pharmacology* / Q000627:therapeutic use; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000819:agonists / Q000378:metabolism*; D015427:Reperfusion Injury / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: C485383:6,7-dihydroxyflavone; D020536:Enzyme Activators; D047309:Flavones; D009569:Nitric Oxide; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D020813:Receptor, trkB; D005978:Glutathione
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