Combination treatment with U0126 and rt-PA prevents adverse effects of the delayed rt-PA treatment after acute ischemic stroke. Academic Article uri icon

Overview

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.

publication date

  • June 7, 2021

Research

keywords

  • Butadienes
  • Hemorrhage
  • Ischemic Stroke
  • Nitriles
  • Tissue Plasminogen Activator

Identity

PubMed Central ID

  • PMC8184783

Scopus Document Identifier

  • 85107547364

Digital Object Identifier (DOI)

  • 10.1038/s41598-021-91469-9

PubMed ID

  • 34099834

Additional Document Info

volume

  • 11

issue

  • 1