Detrimental influence of Arginase-1 in infiltrating macrophages on poststroke functional recovery and inflammatory milieu.

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Tác giả: Won-Suk Chung, Ariandokht Einisadr, Byeong Seong Jang, Seung Ah Jee, Byung Gon Kim, Hyung Soon Kim, Hee Hwan Park, Hyo Gyeong Seo, Yeojin Seo

Ngôn ngữ: eng

Ký hiệu phân loại: 415.95 Inflection

Thông tin xuất bản: United States : Proceedings of the National Academy of Sciences of the United States of America , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 89097

Poststroke inflammation critically influences functional outcomes following ischemic stroke. Arginase-1 (Arg1) is considered a marker for anti-inflammatory macrophages, associated with the resolution of inflammation and promotion of tissue repair in various pathological conditions. However, its specific role in poststroke recovery remains to be elucidated. This study investigates the functional impact of Arg1 expressed in macrophages on poststroke recovery and inflammatory milieu. We observed a time-dependent increase in Arg1 expression, peaking at 7 d after photothrombotic stroke in mice. Cellular mapping analysis revealed that Arg1 was predominantly expressed in LysM-positive infiltrating macrophages. Using a conditional knockout (cKO) mouse model, we examined the role of Arg1 expressed in infiltrating macrophages. Contrary to its presumed beneficial effects, Arg1 cKO in LysM-positive macrophages significantly improved skilled forelimb motor function recovery after stroke. Mechanistically, Arg1 cKO attenuated fibrotic scar formation, enhanced peri-infarct remyelination, and increased synaptic density while reducing microglial synaptic elimination in the peri-infarct cortex. Gene expression analysis of fluorescence-activated single cell sorting (FACS)-sorted CD45
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