Biochanin A, as the Lrg1/TGF-β/Smad2 pathway blockade, attenuates blood-brain barrier damage after cerebral ischemia-reperfusion by modulating leukocyte migration patterns

Background: Biochanin A is an excellent dietary isoflavone that has the concomitant function of both medicine and foodstuff. The attenuation biochanin on blood-brain barrier (BBB) damage induced by cerebral ischemia-reperfusion remains unclear. Methods: C57BL/6 mice were subjected to 1 h middle artery occlusion (MCAO) followed 24 reperfusion. infarct volume brain was stained TTC, while leakage quantitatively Evans blue, neurologic deficit score measured. Microglial-induced morphologic changes observed via immunofluorescence staining, rolling adhering leukocytes in venules two-photon imaging, inner fluorescein isothiocyanate-albumin compared with those surrounding interstitial area through venular albumin leakage. Results: effect tight junction injury or conventional knockdown leucine-rich α2-glycoprotein (Lrg1) mice. could ameliorate BBB a dose-dependent manner strengthening immunostaining occludin, claudin-5, zonula occludens-1. amoeba microglial combined elevated expression Lrg1 be relieved under treatment A. played countervailing role vessel, blood vessels reduced. diminished its functions further improved for Lrg1-knockout mice, as well inhibition effects TGF-β1, phosphorylation suppressor mothers against decapentaplegic 2 (Smad2)/Smad2 western blot assay. Conclusion: alleviate blocked Lrg1/TGF-β/Smad2 pathway modulate leukocyte migration patterns.