Effect of encephalomyosynangiosis procedure on post stroke recovery in a permanent model of ischemic stroke.

Abstract

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 use an indirect intracranial bypass technique via encephalomyosynangiosis (EMS), which involves the transposition of autologous temporalis muscle onto the ischemic cortex to stimulate angiogenesis. EMS has proven effective in moyamoya disease, and we hypothesized that it may provide sustained angiogenesis and functional recovery after AIS. We investigated the therapeutic potential of EMS in a mouse model of cortical ischemia, performed four hours after 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, and novel object recognition tasks. EMS significantly reduced infarct volume at 5&#xa0;days post-stroke compared to dMCAo controls (28.5&#xa0;&#xb1;&#xa0;9.9&#xa0;% vs. 49.3&#xa0;&#xb1;&#xa0;14.5&#xa0;%, p&#xa0;<&#xa0;0.05). At 30&#xa0;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 affect sensorimotor function, but it improved learning and memory performance in novel object recognition tasks. In summary, EMS enhances angiogenesis, cerebral perfusion, and cognitive recovery after AIS in mice. These findings provide proof-of-concept evidence for the first time supporting EMS as a novel surgical strategy for promoting vascular repair and functional recovery following AIS, warranting further translational investigation.