https://www.selleckchem.com/products/gsk2126458.html At day 30, expression levels of IL-1β and tumor necrosis factor (TNF)-α returned to normal levels in the cerebral cortex of septic mice. Interestingly, resolution of neuroinflammation and alleviation of depression were delayed in septic mice treated with FTY720, which inhibits sphingosine-1-phosphate (S1P)-dependent lymphocyte egress from lymph nodes. On analyzing the brain T cells with or without FTY720 in septic mice, the FTY720 untreated mice presented increased regulatory T cells (Treg) and Th2 cells in the brain, whereas the FTY720 treated mice demonstrated increased Th17 in the brain at day 30. Furthermore, in FTY720 treated septic mice, the number of astrocytes in the cerebral cortex remained reduced at day 30. These results suggest that infiltrated Treg and Th2 cells contribute to the attenuation SAE and alleviate SAE-induce mental disorder by resolving neuroinflammation in the chronic phase of sepsis.Previous studies have demonstrated a close association between an altered immune system and major depressive disorders, and inhibition of neuroinflammation may represent an alternative mechanism to treat depression. Recently, the anti-inflammatory activity of ibrutinib has been reported. However, the effect of ibrutinib on neuroinflammation-induced depression and its underlying mechanism has not been comprehensively studied. Therefore, we aimed to elucidate the potential anti-depressive role and mechanism of ibrutinib against neuroinflammation-induced depression and synaptic defects. Our results showed that ibrutinib treatment significantly reduced lipopolysaccharide (LPS)-induced depressive-like behaviors and neuroinflammation via inhibiting NF-kB activation, decreasing proinflammatory cytokine levels, and normalizing redox signaling and its downstream components, including Nrf2, HO-1, and SOD2, as well as glial cell activation markers, such as Iba-1 and GFAP. Further, ibrutinib treatment inhibited LPS-activ