Open AccessLimb Ischemic Perconditioning Attenuates Blood-Brain Barrier Disruption by Inhibiting Activity of MMP-9 and Occludin Degradation after Focal Cerebral Ischemia
Author(s) -
Changhong Ren,
Ning Li,
Brian Wang,
Yong Yang,
Jinhuan Gao,
Sijie Li,
Yuchuan Ding,
Kunlin Jin,
Xunming Ji
Publication year - 2015
Publication title -
aging and disease
Language(s) - English
Resource type - Journals
ISSN - 2152-5250
DOI - 10.14336/ad.2015.0812
Subject(s) - occludin , blood–brain barrier , ischemia , western blot , medicine , tight junction , neuroprotection , matrix metalloproteinase , claudin , neuroinflammation , brain ischemia , pharmacology , anesthesia , microbiology and biotechnology , inflammation , chemistry , central nervous system , biology , biochemistry , gene
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.