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- W3199630022 abstract "Traumatic brain injury (TBI) and cerebrovascular injury are leading causes of disability and mortality worldwide. Systemic infections often accompany these disorders and can worsen outcomes. Recovery after brain injury depends on innate immunity, but the effect of infections on this process is not well understood. Here, we demonstrate that systemically introduced microorganisms and microbial products interfered with meningeal vascular repair after TBI in a type I interferon (IFN-I)-dependent manner, with sequential infections promoting chronic disrepair. Mechanistically, we discovered that MDA5-dependent detection of an arenavirus encountered after TBI disrupted pro-angiogenic myeloid cell programming via induction of IFN-I signaling. Systemic viral infection similarly blocked restorative angiogenesis in the brain parenchyma after intracranial hemorrhage, leading to chronic IFN-I signaling, blood–brain barrier leakage and a failure to restore cognitive–motor function. Our findings reveal a common immunological mechanism by which systemic infections deviate reparative programming after central nervous system injury and offer a new therapeutic target to improve recovery. Traumatic brain injury and stroke are commonly complicated by systemic infections, which impede recovery and lead to poor clinical outcomes. Using a mouse model, McGavern and colleagues show systemic microbial infections impair central nervous system revascularization and repair by a mechanism involving type I interferon signaling." @default.
- W3199630022 created "2021-09-27" @default.
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- W3199630022 date "2021-09-23" @default.
- W3199630022 modified "2023-10-16" @default.
- W3199630022 title "Antimicrobial immunity impedes CNS vascular repair following brain injury" @default.
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- W3199630022 doi "https://doi.org/10.1038/s41590-021-01012-1" @default.
- W3199630022 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8488012" @default.
- W3199630022 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34556874" @default.
- W3199630022 hasPublicationYear "2021" @default.
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