Post-stroke rapamycin treatment improves post-recanalization cerebral blood flow and outcome in rats

Abstract

AbstractIschaemic stroke treatment is limited to recanalizing the occluded vessel, while there is no approved adjunctive cerebroprotective therapy to protect either the neurons and parenchyma or the neurovascular unit. Pharmacological inhibition of mammalian target of rapamycin-1 (mTORC1) with rapamycin has shown promise in reducing infarct volume and improving functional outcomes. However, previous studies that investigated the effects of rapamycin on the vasculature and cerebral blood flow (CBF), administered rapamycin prior to or during stroke induction, thus limiting the potential for clinical translation. Therefore we investigated whether rapamycin maintains its cerebrovascular protective effect when administered immediately after recanalization following 90 minutes stroke in Wistar rats. We show, that rapamycin significantly improved post-recanalization cerebral blood flow (CBF), suggesting a beneficial neurovascular effect of rapamycin. Rats treated with rapamycin had smaller infarct volumes and improved functional outcomes compared to the control animals at three days post-stroke. The mechanisms of the overall positive effects seen in this study are likely due to rapamycin’s hyperacute effects on the neurovasculature, as shown with increased CBF during this phase. This paper shows that rapamycin treatment is a promising adjunct cerebroprotective therapy option for ischemic stroke.