12/15-lipoxygenase inhibition attenuates neuroinflammation by suppressing inflammasomes

Introduction Lipoxygenases (LOXs) have essential roles in stroke, atherosclerosis, diabetes, and hypertension. 12/15-LOX inhibition was shown to reduce infarct size brain edema the acute phase of experimental stroke. However, significance on neuroinflammation, which has an role pathophysiology not been clarified yet. Methods In this study, ischemia/recanalization (I/R) performed by occluding proximal middle cerebral artery (pMCAo) mice. Either inhibitor (ML351, 50 mg/kg) or its solvent (DMSO) injected i.p. at recanalization after 1 h occlusion. Mice were sacrificed 6, 24, 72-h ischemia induction. Infarct volumes calculated Nissl-stained sections. Neurological deficit scoring used for functional analysis. Lipid peroxidation determined MDA assay, inflammatory cytokines IL-6, TNF-alpha, IL-1beta, IL-10, TGF-beta quantified ELISA. The inflammasome proteins NLRP1 NLRP3, 12/15-LOX, caspase-1 detected with immunofluorescence staining. Results volumes, neurological scores, lipid significantly attenuated ML351-treated groups 72-h. ELISA results revealed that pro-inflammatory TNF-alpha decreased 6-h and/or 24-h I/R, while anti-inflammatory IL-10 increased ML351 treatment. NLRP3 immunosignaling enhanced three time points diminished application. Interestingly, immunoreactivity more pronounced than NLRP1. Hence, we proceeded study co-localization caspase-1, indicated co-localized signaling. Additionally, found neurons all but non-neuronal cells 72 I/R. Discussion These suggest suppresses ischemia-induced inflammation subacute phases stroke via suppressing activation. Understanding mechanisms underlying associated pathways, like activation, may broader implications treatment other diseases characterized neuroinflammation.