Interleukin-1 receptor-1 signaling mediates neuroinflammation, neuronal injury, and cognitive decline after diffuse traumatic brain injury - PubMed
12 hours ago
- #interleukin-1 receptor
- #neuroinflammation
- #traumatic brain injury
- Interleukin-1 receptor-1 (IL-1R1) signaling plays a key role in neuroinflammation, neuronal injury, and cognitive decline following diffuse traumatic brain injury (TBI).
- The study used wild-type and IL-1R1 knock-out (KO) mice to assess the effects of TBI at 3, 7, and 30 days post-injury (dpi).
- IL-1R1KO reduced TBI-associated increases in leukocytes in the brain and neurofilament light chain (NfL) in plasma at 3 dpi.
- At 7 dpi, IL-1R1KO attenuated TBI-induced increases in inflammatory markers (Il1b, Tnfa, Irf7) in the hippocampus and cortex.
- TBI impaired cued fear memory and increased NfL in plasma at 7 dpi, both of which were mitigated by IL-1R1KO.
- Single nuclei RNA-seq revealed TBI-induced changes in gene expression in the hippocampus, with many effects prevented by IL-1R1KO.
- IL-1R1-dependent neuronal dysfunction was observed, including decreased neuronal activation (pCREB) and impaired fear conditioning at 30 dpi.
- The study highlights IL-1R1 as a potential therapeutic target for mitigating TBI-related cognitive deficits.