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Abstract Angiogenic factors associated with Moyamoya disease (MMD) are overexpressed in M2 polarized microglia in ischemic stroke, suggesting that microglia may be involved in the pathophysiology of MMD; however, existing approaches are not applicable to explore this hypothesis. Herein we applied blood induced microglial-like (iMG) cells. We recruited 25 adult patients with MMD and 24 healthy volunteers. Patients with MMD were subdivided into progressive (N = 7) or stable (N = 18) group whether novel symptoms or radiographic advancement of Suzuki stage within 1 year was observed or not. We produced 3 types of iMG cells; resting, M1-, and M2-induced cells from monocytes, then RNA sequencing followed by GO and KEGG pathway enrichment analysis and qPCR assay were performed. RNA sequencing of M2-induced iMG cells revealed that 600 genes were significantly upregulated (338) or downregulated (262) in patients with MMD. Inflammation and immune-related factors and angiogenesis-related factors were specifically associated with MMD in GO analysis. qPCR for MMP9, VEGFA, and TGFB1 expression validated these findings. This study is the first to demonstrate that M2 microglia may be involved in the angiogenic process of MMD. The iMG technique provides a promising approach to explore the bioactivity of microglia in cerebrovascular diseases.

Abstract Aim Several studies reported stress‐induced microglial phagocytosis, but the biochemical mechanisms by which stress alters microglial synaptic phagocytosis are not fully uncovered. Local or limited apoptosis without cell death was observed at neuronal synapses in previous studies, and proposed as an upstream mechanism for microglial synapse elimination. In this micro‐report, we aimed to preliminary examine local synaptic apoptosis in the mouse hippocampus following severe restraint stress, and its effect on microglial phagocytosis. Methods Mice were exposed to 10‐day water immersion restraint stress (WIRS). Brain sections including stratum lucidum in the hippocampal CA3 subfield were stained with antibodies against cleaved caspase 3, ionized calcium‐binding adapter molecule1 (Iba1), lysosomal‐associated membrane protein1 (LAMP1), vesicular glutamate transporter1 (VGLUT1). Co‐localization among these proteins were calculated. Results Our image analysis revealed that synaptic apoptosis was increased while there were no significant changes in microglial phagocytic activity and synaptic phagocytosis following 10‐day WIRS. Conclusion Severe restraint stress enhanced pre‐synaptic apoptosis in mouse CA3 stratum lucidum region, but did not promote microglial phagocytosis. The phenomenon microglia fail to phagocytose weakened and unnecessary synapses may be related to pathology of stress.