Abstract WP361: Effect of indirect encephalomyosynangiosis (EMS) on post stroke recovery in a permanent model of ischemic stroke

Background: Acute ischemic stroke (AIS) remains a leading cause of disability worldwide. Limited treatments for AIS with thrombolytics are further constrained by narrow therapeutic windows and no neuroprotective effects. Damaged or underdeveloped vasculature and poor angiogenesis after AIS remains a major cause of failed neuroprotective therapy after AIS. There is a critical need for alternative approaches that enhance angiogenesis and neuroprotection to improve post-stroke recovery. Here we want to use an indirect EMS surgical technique, which involves the transposition of autologous temporalis muscle onto the ischemic cortex to stimulate angiogenesis. EMS has proven effective in moyamoya disease in clinics, and we hypothesize that it may provide sustained angiogenesis and functional recovery after AIS. Methods: We investigated the therapeutic potential of indirect EMS in a mouse model of cortical ischemia induced by permanent distal middle cerebral artery occlusion (dMCAo). Forty-two male and female C57BL/6 mice were randomized into sham, dMCAo, and dMCAo+EMS groups. Outcomes were assessed by infarct volume quantification, cerebral perfusion imaging (laser speckle), immunohistochemical analyses of vascular density and inflammatory response, and neurobehavioral testing using open field, rotarod, novel object recognition task. Results: indirect EMS significantly reduced infarct volume at 5 days post-stroke compared to dMCAo controls (28.5 ± 9.9% vs. 49.3 ± 14.5%, p<0.05). At 30 days, EMS-treated mice demonstrated improved cerebral perfusion in perilesional regions and increased blood vessel density, accompanied by reduced IBA1+ cell accumulation. While EMS did not significantly reduce long-term cortical atrophy or enhance sensorimotor recovery, it improved learning and memory performance in novel object recognition tasks. Conclusion: Indirect EMS enhances angiogenesis, cerebral perfusion, and cognitive recovery after AIS in mice. These findings provide proof-of-concept evidence for the first time supporting indirect EMS as a novel surgical strategy for promoting vascular repair by swift angiogenesis and functional recovery following AIS, warranting further translational investigation.