Abstract WP261: Encephalomyosynangiosis Improves Angiogenesis And Recovery In Mice After Transient Ischemic Stroke

Abstract

Background and Purpose: The ability of the brain to self-heal after stroke is limited by inadequate blood supply and acute inflammation. Hence, we hypothesized that improved blood supply via promoting neoangiogenesis will reduce acute inflammation and improve recovery after stroke. Encephalomyosynangiosis (EMS) is a neurosurgical procedure that achieves angiogenesis with low morbidity in patients with moyamoya disease, reducing risk of stroke. EMS has never been studied in ischemic stroke. Here, we developed a novel model of EMS after ischemic stroke induced by middle cerebral artery occlusion model (MCAo) in mice. We demonstrated that this novel EMS procedure can induce angiogenesis and improve recovery after stroke. Methods: After 60 minutes of MCAo, mice were randomized to MCAo or MCAo+EMS groups. After 3-4 hours, EMS was performed. In brief, EMS involves a craniotomy and placement of a vascular temporalis muscle flap on the pial surface of the ischemic brain. Mice were sacrificed at day 7 or 21 after MCAo. Viability of temporalis muscle was measured using a nicotinamide adenine dinucleotide reduced tetrazolium reductase assay. ARY015 Proteome Profiler Mouse Angiogenesis Array (R&D Systems) was used to quantify angiogenic and neuromodulating protein expression. Immunohistochemistry was used to visualize immune infiltration by measuring F4/80 positive macrophages. Results: EMS after ischemic stroke did not increase mortality despite dual invasive surgery. Grafted temporalis muscle remained viable up to 21 days after EMS. We found a significant increase in FGF-acidic (0.677±0.007 vs. 0.585±0.014, p=0.045) and decrease in osteopontin (0.692±0.007 vs. 0.758±0.014, p=0.048) protein levels in the MCAo+EMS group 21 days after stroke, suggesting improved angiogenesis and recovery respectively. Mice in the MCAo+EMS group also showed reduced F4/80+ve macrophage accumulation in the peri-lesional territory of ischemic tissue, suggesting attenuated inflammation after stroke. Conclusions: These proof-of-concept data support that our novel EMS procedure is well-tolerated and may improve angiogenesis and recovery after stroke. EMS after MCAo is a promising new method of improving angiogenesis and recovery after stroke.