Research output per year
Research output per year
Cyrille Orset, Kajsa Arkelius, Antoine Anfray, Karin Warfvinge, Denis Vivien, Saema Ansar
Research output: Contribution to journal › Article › peer-review
In acute ischemic stroke, the only FDA-approved drug; recombinant tissue plasminogen activator (rt-PA) is limited by restricted time-window due to an enhanced risk of hemorrhagic transformation which is thought to be caused by metalloproteinase (MMP). In experimental stroke inhibitors of the mitogen–activated protein kinase kinase extracellular signal–regulated kinase kinase (MEK) 1/2 pathways reduce the MMPs. This study evaluated whether a MEK1/2 inhibitor in combination with rt-PA can prevent the detrimental effects of delayed rt-PA therapy in stroke. Thromboembolic stroke was induced in C57 black/6J mice and the MEK1/2 inhibitor U0126 was administrated 3.5 h and rt-PA 4 h post stroke-onset. Treatment with rt-PA demonstrated enhanced MMP-9 protein levels and hemorrhagic transformation which was prevented when U0126 was given in conjunction with rt-PA. By blocking the MMP-9 with U0126 the safety of rt-PA administration was improved and demonstrates a promising adjuvant strategy to reduce the harmful effects of delayed rt-PA treatment in acute ischemic stroke.
Original language | English |
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Article number | 11993 |
Journal | Scientific Reports |
Volume | 11 |
DOIs | |
Publication status | Published - 2021 Dec |
Research output: Thesis › Doctoral Thesis (compilation)