Rosiglitazone Protects Blood-Brain Barrier Integrity Following Ischemic Stroke by Reducing MMP-9 Expression Through a Caveolin-1-Dependent Pathway.

Abstract

Background: Rosiglitazone (RSG) is a widely used antidiabetic drug which activates peroxisome proliferator-activated receptor-γ. Recent work have shown that RSG can up-regulate caveolin-1 levels and ameliorate both chronic and acute brain injury. However, whether rosiglitazone can ameliorate ischemic injury in the brain via a caveolin-1-dependent pathway remains unknown.Methods: Adult male sprague-dawley rats were randomly divided into sham operation group, model group, rosiglitazone group and rosiglitazone+daidzein group. The rat models of middle cerebral artery occlusion (MCAO) was established using the suture method, with ischemia for 2 hours and reperfusion for 22 hours. Neurological deficits were evaluated by the methods of Longa’s standard scoring. Cerebral infarction volume was observed by staining with 2, 3, 5-triphenyltetrazolium chloride. Evans blue content reflects BBB permeability. The expressions of caveolin-1, matrix metalloproteinase-9(MMP-9) and occludin were detected by immunofluorescent staining and western blot.Results: In this study, we found that the expression of caveolin-1 was increased in a rat model of stroke, and treatment with RSG significantly increased the levels of caveolin-1, reduced the release of MMP-9, and increased the expression of occludin. On the other hand, a caveolin-1 inhibitor daidzein canceled the protective roles of RSG in the MCAO model.Conclusions: These data unveil that RSG might protect blood-brain barrier integrity by down-regulating the levels of MMP-9 via a caveolin-1-dependent pathway.