title: Overexpression of Fibulin-5 Attenuates Ischemia/Reperfusion Injury After Middle Cerebral Artery Occlusion in Rats.
abstract: Ischemia/reperfusion (I/R) injury after middle cerebral artery occlusion (MCAO) induces detrimental processes such as oxidative stress, inflammation, and apoptosis. All parts of the neurovascular unit are involved in these pathological processes. Fibulin-5 is a 66-kD glycoprotein secreted by various vascular cells, including vascular smooth muscle cells (SMCs), fibroblasts, and endothelial cells. As an extracellular matrix protein involved in cell adhesion, fibulin-5 has been widely studied in tumor growth and invasion. However, the effects of fibulin-5 on brain injury following ischemia/reperfusion have not been reported. In this study, we examined the effect of overexpressed fibulin-5 on reactive oxygen species (ROS) production. Fibulin-5 overexpression attenuated ROS expression, which in turn decreased apoptosis and blood-brain barrier (BBB) permeability following MCAO and reperfusion. Fibulin-5 also improved neurological deficits but had no effect on infarction volume. T2-weighted MRI and electron microscopy further confirmed brain edema reduction and decreased BBB disruption in fibulin-5 overexpression recombinant adenovirus (Ad-FBLN) treated rats. In addition, tight junction protein occludin was significantly degraded and matrix metalloproteinase 9 (MMP-9) immunoreactivity was significantly increased. Fibulin-5-mediated ROS decrease was not due to increased total superoxide dismutase levels but was instead correlated with the activation of Rac-1 pathway. The findings highlight the importance of antioxidant mechanism underlying cerebral ischemia/reperfusion.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, No. 1 You Yi Road, Chongqing, 400016, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, No. 1 You Yi Road, Chongqing, 400016, China.
authors.forename: Chuang
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Department of Medicine, Drexel University College of Medicine, Philadelphia, PA, 19129, USA.
authors.forename: Cindy Si
authors.initials: CS
authors.lastname: Chen
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, No. 1 You Yi Road, Chongqing, 400016, China.
authors.forename: Xiangfeng
authors.initials: X
authors.lastname: Xing
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, No. 1 You Yi Road, Chongqing, 400016, China.
authors.forename: Guanghui
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, No. 1 You Yi Road, Chongqing, 400016, China.
authors.forename: Jinzhou
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, No. 1 You Yi Road, Chongqing, 400016, China. qinxinyue01@163.com.
authors.forename: Xinyue
authors.initials: X
authors.lastname: Qin
mesh_terms: D000256:Adenoviridae / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001929:Brain Edema / Q000150:complications / Q000378:metabolism / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000150:complications / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000150:complications* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D062793:Occludin / Q000378:metabolism; D010766:Phosphorylation; D059748:Proteolysis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D011995:Recombination, Genetic / Q000235:genetics; D015427:Reperfusion Injury / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D020521:Stroke / Q000150:complications / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D062793:Occludin; D017382:Reactive Oxygen Species; C060820:fibulin; D013482:Superoxide Dismutase; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D020780:Matrix Metalloproteinase 9; D020830:rac1 GTP-Binding Protein
keywords: Apoptosis; Blood–brain barrier; Fibulin-5; Ischemia/reperfusion; ROS; Rac-1