Rho-kinase inhibitors do not expand hematoma volume in acute experimental intracerebral hemorrhage

Murtaza Akhter, Tom Qin, Paul Fischer, Homa Sadeghian, Hyung Hwan Kim, Michael J. Whalen, Joshua N. Goldstein, Cenk Ayata

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Rho-associated kinase (ROCK) is an emerging target in acute ischemic stroke. Early pre-hospital treatment with ROCK inhibitors may improve their efficacy, but their antithrombotic effects raise safety concerns in hemorrhagic stroke, precluding use prior to neuroimaging. Therefore, we tested whether ROCK inhibition affects the bleeding times, and worsens hematoma volume in a model of intracerebral hemorrhage (ICH) induced by intrastriatal collagenase injection in mice. Tail bleeding time was measured 1 h after treatment with isoform-nonselective inhibitor fasudil, or ROCK2-selective inhibitor KD025, or their vehicles. In the ICH model, treatments were administered 1 h after collagenase injection. Although KD025 but not fasudil prolonged the tail bleeding times, neither drug expanded the volume of ICH or worsened neurological deficits at 48 h compared with vehicle. Although more testing is needed in aged animals and comorbid models such as diabetes, these results suggest ROCK inhibitors may be safe for pre-hospital administration in acute stroke.

Original languageEnglish (US)
Pages (from-to)769-776
Number of pages8
JournalAnnals of Clinical and Translational Neurology
Volume5
Issue number6
DOIs
StatePublished - Jun 2018

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Clinical Neurology

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