Cerebrolysin Ameliorates BBB Leakage and Microvascular Inflammation Induced by tPA and Fibrin
Chopp M, Li C, Teng H, Zhang L, and Zhang Z. Cerebrolysin Ameliorates BBB Leakage and Microvascular Inflammation Induced by tPA and Fibrin. Eur J Neurol 2019; 26:20.
Eur J Neurol
Background and aims: Fibrin deposition post stroke and thrombolysis with tPA induce blood brain barrier (BBB) permeability and subsequent perfusion deficits and proinflammatory conditions. Here, using a human brain cerebral endothelial cell BBB assay, we investigated the effect of Cerebrolysin on BBB integrity and its underlying molecular contributions to ameliorating vascular permeability induced by tPA and fibrin. Methods: Human primary brain endothelial cells (150,000/ cm2) were seeded onto a transwell and treated with tPA (10ug/ml) or fibrin (1.5ug/ml), alone or with Cerebrolysin (5, 10, 20, 40, 80 ul/ml; n=3 per experiment). Leakage of FITC-labeled dextran (70KD) into a bottom chamber of the transwell was quantified. Results: Treatment of human cerebral endothelial cells with fibrin and tPA significantly (p<0.05) increased BBB leakage by 37% and 57%, respectively, compared to the nontreatment group (n-3/group). However, Cerebrolysin in a dose-dependent manner significantly decreased fibrin- or tPA-induced leakage, respectively, at a dose of 20 ul/ms. Western blot analysis showed that compared to non-treated control, fibrin and tPA alone markedly augmented proinflammatory proteins, i.e., HMGB1 ICAM-1, TNFα, and pNFκB. However, Cerebrolysin significantly (P<0.05) decreased these elevated adverse proinflammatory proteins. Conclusion: Cerebrolysin reduces BBB permeability induced by tPA and fibrin. Our data also provide molecular bases for the beneficial effect of Cerebrolysin on reduction of BBB leakage. Thus, in vivo studies employing Cerebrolysin in combination with tPA and/or thrombectomy for the treatment of stroke are warranted.