Abstract
Abstract Aged traumatic brain injury (TBI) patients suffer increased mortality and long-term neurocognitive/neuropsychiatric morbidity than younger patients. Microglia, the resident macrophages of the brain, are complicit in both. We hypothesized that aged microglia would fail to return to a homeostatic state after TBI and adopt a long-term, injury-associated state within aged brains compared to young brains after TBI. Young and aged male C57BL/6 mice underwent TBI via controlled cortical impact vs. sham injury and were sacrificed four months post-TBI. We utilized single-cell RNA sequencing to examine age-associated cellular responses after TBI. Brains were harvested with CD45+ cells isolated via florescence-activated cell sorting. cDNA libraries were prepared via the 10x Genomics Chromium Single Cell 3’ Reagent Kit, followed by sequencing on a HiSeq 4000 instrument and computation analyses. Post-injury, aged mice demonstrated a proportional decrease in homeostatic microglia, and greater increased infiltrating T cells compared to young-adult mice. Of note, aged mice post-injury had a subpopulation of age-specific, immune-inflammatory microglia resembling gene profiles of neurodegenerative disease-associated microglia with enriched pathways involving in leukocyte recruitment. Contrastingly, post-injury, aged mice demonstrate a heterogenous T-cell infiltration with gene profiles corresponding to CD8 effector memory, CD8 native-like, CD4, and double-negative T cells and enriched pathways such as macromolecule synthesis. Taken together, our data showed that age-specific gene signature changes in the T-cell infiltrates and the microglial subpopulation contribute to increased vulnerability of the aged brain to TBI. Supported by R01 GM130662
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.