Combination treatment with U0126 and rt-PA prevents adverse effects of the delayed rt-PA treatment after acute ischemic stroke

Cyrille Orset, Kajsa Arkelius, Antoine Anfray, Karin Warfvinge, Denis Vivien, Saema Ansar

Research output: Contribution to journalArticlepeer-review

Abstract

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 languageEnglish
Article number11993
JournalScientific Reports
Volume11
DOIs
Publication statusPublished - 2021 Dec

Subject classification (UKÄ)

  • Neurology
  • Neurosciences
  • Cardiac and Cardiovascular Systems

Fingerprint

Dive into the research topics of 'Combination treatment with U0126 and rt-PA prevents adverse effects of the delayed rt-PA treatment after acute ischemic stroke'. Together they form a unique fingerprint.

Cite this