Acute brain insults elicit pronounced inflammation that amplifies brain damage in intracerebral hemorrhage (ICH). We profiled perihematomal tissue from patients with ICH, generating a molecular landscape of the injured brain, and identified formyl peptide receptor 1 (FPR1) as the most abundantly increased damage-associated molecular pattern (DAMP) receptor, predominantly expressed by microglia. Circulating mitochondrial N-formyl peptides, endogenous ligands of FPR1, were augmented and correlated with the magnitude of brain edema in patients with ICH. Interactions of formyl peptides with FPR1 activated microglia, boosted neutrophil recruitment, and aggravated neurological deficits in two mouse models of ICH. We created an FPR1 antagonist T-0080 that can penetrate the brain and bind both human and murine FPR1. T-0080 attenuated brain edema and improved neurological outcomes in ICH models. Thus, FPR1 orchestrates brain inflammation after ICH and could be targeted to improve clinical outcome in patients.

急性脑损伤引起明显的炎症，放大脑出血 (ICH) 中的脑损伤。我们分析了 ICH 患者的血肿周围组织，生成了受伤大脑的分子图谱，并确定甲酰肽受体 1 (FPR1) 是增加最多的损伤相关分子模式 (DAMP) 受体，主要由小胶质细胞表达。循环线粒体NFPR1 的内源性配体 - 甲酰肽被增强并与 ICH 患者脑水肿的严重程度相关。甲酰肽与 FPR1 的相互作用激活了小胶质细胞，促进了中性粒细胞的募集，并加重了两种 ICH 小鼠模型的神经功能缺损。我们创造了一种 FPR1 拮抗剂 T-0080，它可以穿透大脑并结合人和鼠 FPR1。T-0080 减轻脑水肿并改善 ICH 模型中的神经学结果。因此，FPR1 协调 ICH 后的脑部炎症，可用于改善患者的临床结果。