miR-195 Has a Potential to Treat Ischemic and Hemorrhagic Stroke through Neurovascular Protection and Neurogenesis

Abstract

Tissue plasminogen activator is the only U.S. FDA-approved therapy for ischemic stroke, while there is no specific medication for hemorrhagic stroke. Therefore, the treatment of acute stroke continues to be a major unmet clinical need. We explored the effects of miR-195 on neurovascular protection and its potential in treating acute stroke. Using both cellular and animal studies, we showed that miR-195’s beneficial effects are mediated by four mechanisms: (1) anti-apoptosis for injured neural cells by directly suppressing Sema3A/Cdc42/JNK signaling, (2) neural regeneration by promoting neural stem cell proliferation and migration, (3) anti-inflammation by directly blocking the NF-kB pathway, and (4) improvement of endothelial functions. We intravenously injected miR-195 carried by nanoparticles into rats with either ischemic or hemorrhagic stroke in the acute stage. The results showed that miR-195 reduced the size of brain damage and improved functional recovery in both types of stroke rats. The reduction of injured brain volume could be up to 45% in ischemic stroke and approximately 30% in hemorrhagic stroke. The therapeutic window between stroke onset and miR-195 treatment could be up to 6 h. Our data demonstrated that miR-195 possesses the potential to become a new drug to treat acute ischemic and hemorrhagic stroke. Keywords: microRNA, stroke, neuroprotection, neural stem cell, Sema3A