Fluoxetine attenuates neuroinflammation in early brain injury after subarachnoid hemorrhage: a possible role for the regulation of TLR4/MyD88/NF-B signaling pathway

BackgroundNeuroinflammation is closely associated with functional outcome in subarachnoid hemorrhage (SAH) patients. Our recent study demonstrated that fluoxetine inhibited NLRP3 inflammasome activation and attenuated necrotic cell death in early brain injury after SAH, while the effects and potential mechanisms of fluoxetine on neuroinflammation after SAH have not been well-studied yet.MethodsOne hundred and fifty-three male SD rats were subjected to the endovascular perforation model of SAH. Fluoxetine (10mg/kg) was administered intravenously at 6h after SAH induction. TAK-242 (1.5mg/kg), an exogenous TLR4 antagonist, was injected intraperitoneally 1h after SAH. SAH grade, neurological scores, brain water content, Evans blue extravasation, immunofluorescence/TUNEL staining, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot were performed.ResultsFluoxetine administration attenuated BBB disruption, brain edema, and improved neurological function after SAH. In addition, fluoxetine alleviated the number of Iba-1-positive microglia/macrophages, neutrophil infiltration, and cell death. Moreover, fluoxetine reduced the levels of pro-inflammatory cytokines, downregulated the expression of TLR4 and MyD88, and promoted the nuclear translocation of NF-B p65, which were also found in rats with TAK-242 administration. Combined administration of fluoxetine and TAK-242 did not enhance the neuroprotective effects of fluoxetine.ConclusionFluoxetine attenuated neuroinflammation and improved neurological function in SAH rats. The potential mechanisms involved, at least in part, TLR4/MyD88/NF-B signaling pathway.