Delayed Recanalization Promotes Functional Recovery in Rats Following Permanent Middle Cerebral Artery Occlusion

Abstract

Most large vessel stroke patients have permanent occlusion, for which there are no current treatment options. Recent case studies have indicated delayed recanalization, that is recanalization outside of the 6-h treatment window, may lead to improved outcome. We hypothesized that delayed recanalization will restore cerebral blood flow, leading to improved function in rats. Male SD rats were subjected to pMCAO or sham surgery. Delayed recanalization was performed on either day 3, 7, or 14 after pMCAO in a subset of animals. Cerebral blood flow was monitored during suture insertion, during recanalization, and then at sacrifice. Neurological function was evaluated for 1 week after delayed recanalization and at 4 weeks post-ictus. After sacrifice, cerebral morphology was measured. Compared to no treatment, delayed recanalization restored cerebral blood flow, leading to sensorimotor recovery, improved learning and memory, reduced infarct volume, and increased neural stem/progenitor cells within the infarction. The data indicate that earlier delayed recanalization leads to better functional and histological recovery. Yet, even restoring cerebral blood flow 14 days after pMCAO allows for rats to regain sensorimotor function. This exploratory study suggests that delayed recanalization may be a viable option for treatment of permanent large vessel stroke.