Therefore, we hypothesize that FOXO1-regulated microglia may potentially exacerbate brain damage and depression post-TBI while PI3K/Akt, TLR/NF-κB or AMPK/SIRT1 signaling pathways may interact with FOXO1 to regulate neutrophil activities in TBI requiring further investigation. This evidence concerns the gene NFKB1 and major depressive disorder.