Inhibition of chemokine-like factor 1 improves bloodbrain barrier dysfunction in rats following foca

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OBJECTIVE To investigate the role of chemokine-like factor 1(CKLF1),a novel C-C chemokine,on brain-blood barrier(BBB)integrity in rat focal cerebral ischemia and reperfusion model.METHODS Antibodies against CKLF1 was applied to the rightcerebral ventricle immediately after transient middle cerebral artery occlusion.Brain water content,Evans blue leakage and the expression of aquaporin-4(AQP-4),matrix metalloproteinase-9(MMP-9),zonula occludens-1(ZO-1)and occludin were measured.RESULTS After treatment with antiCKLF1 antibody,brain water content and Evans blue leakage in ipsilateral hemisphere were decreased in a dose-dependent manner at 24 h after reperfusion,but not changed in contralateral hemisphere.Anti-CKLF1 antibody reduced the expression of AQP-4 and MMP-9,and upregulated the expression of ZO-1 and Occludin.These results suggest that CKLF1 is involved in BBB disruption after reperfusion.CONCLUSION Inhibition of CKLF1 protects against cerebral ischemia by maintaining BBB integrity,possibly via inhibiting the expression of AQP-4 and MMP-9,and increasing the expression of tight junction protein. OBJECTIVE To investigate the role of chemokine-like factor 1 (CKLF1), a novel CC chemokine, on brain-blood barrier (BBB) ​​integrity in rat focal cerebral ischemia and reperfusion model. METHODS Antibodies against CKLF1 was applied to the right cerebral ventricle immediately after transient middle cerebral artery occlusion. Brain water content, Evans blue leakage and the expression of aquaporin-4 (AQP-4), matrix metalloproteinase- 9 (MMP- 9), zonula occludens- 1 (ZO- 1) and occludin were measured. RESULTS After treatment with antiCKLF1 antibody, brain water content and Evans blue leakage in ipsilateral hemisphere were decreased in a dose-dependent manner at 24 h after reperfusion, but not changed in contralateral hemisphere. Anti-CKLF1 antibody reduced the expression of AQP-4 and MMP-9, and upregulated the expression of ZO-1 and Occludin. These results suggest that CKLF1 is involved in BBB disruption after reperfusion. CONCLUSION Inhibition of CKLF1 protects against cerebral ischemia by maintaining BBB integrity , possibly via inhibiting the expression of AQP-4 and MMP-9, and increasing the expression of tight junction protein.
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