High-Mobility Group Box-1-Induced Angiogenesis After Indirect Bypass Surgery in a Chronic Cerebral Hypoperfusion Model

Abstract

High-mobility group box-1 (HMGB1) is a nuclear protein that promotes inflammation during the acute phase post-stroke, and enhances angiogenesis during the delayed phase. Here, we evaluated whether indirect revascularization surgery with HMGB1 accelerates brain angiogenesis in a chronic cerebral hypoperfusion model. Seven days after hypoperfusion induction, encephalo-myo-synangiosis (EMS) was performed with or without HMGB1 treatment into the temporal muscle. We detected significant increments in cortical vasculature (p < 0.01), vascular endothelial growth factor (VEGF) expression in the temporal muscle (p < 0.05), and ratio of radiation intensity on the operated side compared with the non-operated side after EMS in the HMGB1-treated group than in the control group (p < 0.01). Altogether, HMGB1 with EMS in a chronic hypoperfusion model promoted brain angiogenesis in a VEGF-dependent manner, resulting in cerebral blood flow improvement. This treatment may be an effective therapy for patients with moyamoya disease.