PMID- 26618042 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20151130 LR - 20200929 IS - 2152-5250 (Print) IS - 2152-5250 (Electronic) IS - 2152-5250 (Linking) VI - 6 IP - 6 DP - 2015 Nov TI - Limb Ischemic Perconditioning Attenuates Blood-Brain Barrier Disruption by Inhibiting Activity of MMP-9 and Occludin Degradation after Focal Cerebral Ischemia. PG - 406-17 LID - 10.14336/AD.2015.0812 [doi] AB - Remote ischemic perconditioning (PerC) has been proved to have neuroprotective effects on cerebral ischemia, however, the effect of PerC on the BBB disruption and underlying mechanisms remains largely unknown. To address these issues, total 90 adult male Sprague Dawley (SD) rats were used. The rats underwent 90-min middle cerebral artery occlusion (MCAO), and the limb remote ischemic PerC was immediately applied after the onset of MCAO. We found that limb remote PerC protected BBB breakdown and brain edema, in parallel with reduced infarct volume and improved neurological deficits, after MCAO. Immunofluorescence studies revealed that MCAO resulted in disrupted continuity of claudin-5 staining in the cerebral endothelial cells with significant gap formation, which was significantly improved after PerC. Western blot analysis demonstrated that expression of tight junction (TJ) protein occludin was significantly increased, but other elements of TJ proteins, claudin-5 and ZO-1, in the BBB endothelial cells were not altered at 48 h after PerC, compared to MCAO group. The expression of matrix metalloproteinase (MMP-9), which was involved in TJ protein degradation, was decreased after PerC. Interestingly, phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2), an upstream of MMP-9 signaling, was significantly reduced in the PerC group. Our data suggest that PerC inhibits MMP-9-mediated occludin degradation, which could lead to decreased BBB disruption and brain edema after ischemic stroke. FAU - Ren, Changhong AU - Ren C AD - 1 Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China ; 2 Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA ; 6 Center of Stroke, Beijing Institute for Brain Disorder, Beijing, China ; 7 Beijing Key Laboratory of Hypoxia Translational Medicine. Beijing, China. FAU - Li, Ning AU - Li N AD - 1 Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China ; 6 Center of Stroke, Beijing Institute for Brain Disorder, Beijing, China. FAU - Wang, Brian AU - Wang B AD - 2 Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA. FAU - Yang, Yong AU - Yang Y AD - 3 Department of Herbal Medicine, School of Basic Medical Sciences, Beijing University of Chinese Medicine, Beijing, China. FAU - Gao, Jinhuan AU - Gao J AD - 1 Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China. FAU - Li, Sijie AU - Li S AD - 1 Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China ; 6 Center of Stroke, Beijing Institute for Brain Disorder, Beijing, China. FAU - Ding, Yuchuan AU - Ding Y AD - 4 Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI 48201, USA. FAU - Jin, Kunlin AU - Jin K AD - 1 Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China ; 2 Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA. FAU - Ji, Xunming AU - Ji X AD - 1 Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China ; 5 Cerebrovascular Diseases Research Institute, Xuanwu Hospital, Capital Medical University, Beijing, China. LA - eng PT - Journal Article DEP - 20151117 PL - United States TA - Aging Dis JT - Aging and disease JID - 101540533 PMC - PMC4657812 OTO - NOTNLM OT - blood-brain barrier OT - ischemic stroke OT - matrix metalloproteinases OT - remote ischemic perconditioning OT - tight junction EDAT- 2015/12/01 06:00 MHDA- 2015/12/01 06:01 PMCR- 2015/12/01 CRDT- 2015/12/01 06:00 PHST- 2015/06/15 00:00 [received] PHST- 2015/08/12 00:00 [accepted] PHST- 2015/12/01 06:00 [entrez] PHST- 2015/12/01 06:00 [pubmed] PHST- 2015/12/01 06:01 [medline] PHST- 2015/12/01 00:00 [pmc-release] AID - ad-6-6-406 [pii] AID - 10.14336/AD.2015.0812 [doi] PST - epublish SO - Aging Dis. 2015 Nov 17;6(6):406-17. doi: 10.14336/AD.2015.0812. eCollection 2015 Nov.