Aging-dependent microglial heterogeneity worsens outcomes in models of traumatic brain injury - PubMed
5 hours ago
- #microglia
- #aging
- #traumatic brain injury
- Aged TBI brains show pro-inflammatory NLRP3+ microglia, while young TBI brains have neuroprotective Lysozyme+ microglia.
- This microglial difference is linked to higher mortality and worse recovery in aged TBI mice.
- Multi-omics analysis reveals that enhanced glycolysis and a pro-inflammatory chromatin landscape are connected in NLRP3+ microglia.
- ELF1 is identified as a key transcription factor driving NLRP3+ microglia formation.
- Ablating ELF1 reverses age-related microglial dysfunction and improves TBI outcomes.
- Imeglimin, an antihyperglycemic drug that crosses the blood-brain barrier, inhibits ELF1, reverses microglial phenotype, reduces acute mortality, and enhances functional recovery in aged TBI mice.