RhoA Kinase Inhibition With Fasudil Versus Simvastatin in Murine Models of Cerebral Cavernous Malformations.

ABSTRACT:

Background and purpose

We sought to compare the effect of chronic treatment with commonly tolerated doses of Fasudil, a specific RhoA kinase (ROCK) inhibitor, and simvastatin (with pleiotropic effects including ROCK inhibition) on cerebral cavernous malformation (CCM) genesis and maturation in 2 models that recapitulate the human disease.

Methods

Two heterozygous murine models, Ccm1^+/-Msh2^-/- and Ccm2^+/-Trp53^-/-, were treated from weaning to 4 to 5 months of age with Fasudil (100 mg/kg per day), simvastatin (40 mg/kg per day) or with placebo. Mouse brains were blindly assessed for CCM lesion burden, nonheme iron deposition (as a quantitative measure of chronic lesional hemorrhage), and ROCK activity.

Results

Fasud

SUBMITTER: Shenkar R 

PROVIDER: S-EPMC5183488 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature