LAUSR

Formyl peptide receptor 1 facilitates brain inflammation and can be targeted to attenuate acute neural injury. Curbing inflammation in ICH Intracerebral hemorrhage (ICH) is associated with increased brain inflammation that contributes to exacerbate cell death and neurological deficits. Reducing brain inflammation after ICH could improve clinical outcome. Now, Li et al. performed genome-wide transcriptome sequencing of perihematoma human brain tissue and showed that formyl peptide receptor 1 (FPR1) expression was increased in microglia. In rodent models, FPR1 activation after ICH promoted brain inflammation and increased immune cell recruitment into the brain. The authors developed a blood-brain barrier–permeable FPR1 inhibitor that had therapeutic effects in ICH mice, suggesting that targeting FPR1 could be effective for reducing inflammation and promoting recovery after ICH. 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.