title: Apocynum venetum leaf extract attenuates disruption of the blood-brain barrier and upregulation of matrix metalloproteinase-9/-2 in a rat model of cerebral ischemia-reperfusion injury.
abstract: We investigated the neuroprotective effects of Apocynum venetum leaf extract (AVLE) on a rat model of cerebral ischemia-reperfusion injury and explored the underlying mechanisms. Rats were randomly divided into five groups: sham, ischemia-reperfusion, AVLE125, AVLE250, and AVLE500. Cerebral ischemia was induced by 1.5 h of occlusion of the middle cerebral artery. Cerebral infarct area was measured by tetrazolium staining at 24 and 72 h after reperfusion, and neurological function was evaluated at 24, 48 and 72 h after reperfusion. Pathological changes on the ultrastructure of the blood-brain barrier (BBB) were observed by transmission electron microscopy. BBB permeability was assessed by detecting leakage of Evan's blue (EB) dye in brain tissue. The expression and activities of matrix metalloproteinase (MMP)-9/-2 were measured by western blot analyses and gelatin zymography at 24 h after reperfusion. AVLE (500 mg/kg/day) significantly reduced cerebral infarct area, improved recovery of neurological function, relieved morphological damage to the BBB, reduced water content and EB leakage in the brain, and downregulated the expression and activities of MMP-9/-2. These findings suggest that AVLE protects against cerebral ischemia-reperfusion-induced injury by alleviating BBB disruption. This action may be due to its inhibitory effects on the expression and activities of MMP-9/-2.
authors.affiliation: Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xiang
authors.forename: Rui
authors.initials: R
authors.lastname: Lan
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Tang
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Chen
authors.forename: Ding-Fang
authors.initials: DF
authors.lastname: Cai
mesh_terms: D000818:Animals; D030010:Apocynum / Q000737:chemistry; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002545:Brain Ischemia / Q000503:physiopathology*; D002544:Cerebral Infarction / Q000473:pathology / Q000517:prevention & control; D015536:Down-Regulation; D005070:Evans Blue; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D051381:Rats; D015427:Reperfusion Injury / Q000503:physiopathology* / Q000517:prevention & control
chemical_list: D018696:Neuroprotective Agents; D010936:Plant Extracts; D005070:Evans Blue; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9