Cerebrolysin has been shown to promote neurovascular protection and repair in preclinical models of
stroke and neural injury and is demonstrating promise for
stroke and neural injury therapeutic application in the clinic. The effect of
Cerebrolysin on the human cerebral endothelial cell function has not been investigated. Using an in-vitro cerebral endothelial cell permeability assay and western blot analyses of tight junction and proinflammatory and procoagulant
proteins, the present study showed that
tissue plasminogen activator (tPA) and
fibrin substantially impaired human cerebral endothelial cell barrier function and increased permeability, which persisted for at least 24 h. western blot analysis revealed that tPA and
fibrin significantly increased proinflammatory and procoagulation
proteins of
intercellular adhesion molecule 1, high mobility group box 1,
tumor necrosis factor α and phosphorylated nuclear factor kappa B-p65, and significantly reduced
tight junction proteins zonular 1,
occludin and
claudin. However,
Cerebrolysin significantly diminished and reversed tPA- and
fibrin-impaired endothelial cell permeability, which was associated with significant reductions of tPA- and
fibrin-augmented proinflammatory and procoagulation
proteins and significant elevations of tPA- and
fibrin-decreased
tight junction proteins. The beneficial effect of
Cerebrolysin appears specific because cerebroprotein hydrolysate, with a distinct
peptide composition, failed to show the reduction of tPA- and
fibrin-impaired permeability. These data indicate that cererbrolysin has a
therapeutic effect on tPA- and
fibrin-impaired cerebral endothelial cell permeability by reducing proinflammatory and procoagulation
proteins and by elevating
tight junction proteins.