TY - JOUR
T1 - Rho-kinase inhibitors do not expand hematoma volume in acute experimental intracerebral hemorrhage
AU - Akhter, Murtaza
AU - Qin, Tom
AU - Fischer, Paul
AU - Sadeghian, Homa
AU - Kim, Hyung Hwan
AU - Whalen, Michael J.
AU - Goldstein, Joshua N.
AU - Ayata, Cenk
N1 - Funding Information:
This work was in part supported by NIH (NS055104), the Fondation Leducq, the Heitman Foundation, and the Ellison Foundation.
Publisher Copyright:
© 2018 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.
PY - 2018/6
Y1 - 2018/6
N2 - 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.
AB - 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.
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U2 - 10.1002/acn3.569
DO - 10.1002/acn3.569
M3 - Article
AN - SCOPUS:85046826623
SN - 2328-9503
VL - 5
SP - 769
EP - 776
JO - Annals of Clinical and Translational Neurology
JF - Annals of Clinical and Translational Neurology
IS - 6
ER -