Mechanistic correlates of the dual tPA-edaravone therapy of tHI injury.

<p>(<b>A–F</b>) Immunostaining of fibrinogen (A–C) and fluorescent images of the Evans Blue dye (D–F) at 4 h after tHI injury in the striatum (St) and cerebral cortex (Ctx) of the ipsilateral hemisphere of vehicle- and E + tPA-treated animals, and the contralateral hemisphere of mice receiving either treatment. This analysis showed that the E + tPA treatment decreased fibrin deposits, perfusion deficits, and extravasation of the Evans Blue dye. (<b>G</b>) Quantification of malondialdehyde (MDA) at 24 h post-tHI showed significant reduction of lipid peroxidation by the E + tPA treatment. (<b>H</b>) MMP zymography at 24 h post-tHI and quantification showed significant reduction of MMP-9 activity by the E + tPA treatment (n = 4 for each). Equal loading of brain extracts was verified by immunoblot detection of β-actin. L: contralateral (left) hemisphere; R: The ipsilateral (right) hemisphere. (<b>I–K</b>) Real time RT-PCR showed that the E + tPA treatment significantly decreased tHI-induced IL-1β, IL-6, and Tspo transcripts at 24 h recovery (n = 4 each).