Abstract 2628: Remote Ischemic Conditioning Reduces Brain Edema in Experimental Ischemia/Reperfusion Injury

Abstract

Background and Purpose _Remote ischemic conditioning (RIC) has been shown to provide neuroprotective effects, but the precise mechanisms underlying the therapeutic effects still remain unclear. In this study, we investigate changes in blood-brain barrier (BBB) permeability and edema formation, in association with expression of matrix metalloproteinases (MMP), tight junction proteins and aquaporins (AQP) in RIC treated rats following unilateral middle cerebral artery (MCA) occlusion and reperfusion. Methods _Ischemic stroke model was generated by occlusion of the right MCA for 1.5 hours in male Sprague-Dawley rats. Remote ischemic conditioning was conducted immediately after MCA occlusion in the bilateral lower limb by occluding and releasing the femoral artery for three cycles; each occlusion and release lasted for 10 minutes. Edema levels and BBB integrity were studied by quantification of brain water content and extravasations of Evans blue at 48 hours after reperfusion, respectively. Protein expression of occludin, claudin-5, ZO-1, MMP-2, MMP-9, as well as AQP-4 and AQP-9, were determined by Western blot analysis at 48 hours after reperfusion. The activity of MMP-2 and MMP-9 were determined by gelatin zymography at the same time points. Results _Treatment with RIC significantly ( P <0.05) reduced brain edema ( P <0.01) and BBB dysfunction when compared to the control ischemic groups. IPC treatment resulted in a significant ( P <0.05) increase in the expression of tight junction protein occludin in comparison to the control non-treatment group. The expressions of claudin-5 and ZO-1were not different between RIC-treated group and control group. RIC treatment diminished ischemia-induced MMP-9 ( P <0.01) but not MMP-2. The expressions of AQP-4 and AQP-9 were not different between RIC-treated group and control group. Conclusions _RIC ameliorates brain edema and BBB disruption after stroke, in association with a reduction of MMP-9 and increase in the expression of tight junction protein occludin. These results provide clues to neuroprotective properties of RIC.