Research on the Mechanism by Which Lysophosphatidylcholine Regulates the Inflammatory Response in Ischemic Stroke Through the NF-κB Signaling Pathway

Background: Neuroinflammation following ischemic stroke is a significant factor leading to secondary brain damage, but the role of lysophosphatidylcholine (LPC) in this process remains unclear. This study sought to determine whether LPC participates in the post-ischemic inflammatory process and to evaluate if this effect is mediated through the nuclear factor-κB (NF-κB) signaling pathway.Methods: For the in vivo study, male C57BL/6 mice aged 8–10 weeks were randomly assigned to a sham group (n = 10) and a middle cerebral artery occlusion model group (MCAO, n = 10). The suture occlusion method was applied to induce MCAO, with 60 min of ischemia followed by 24 h of reperfusion. LPC concentrations in serum and brain tissue were measured using ELISA. The protein levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in cerebral tissue, together with the expression of nuclear factor-κB (NF-κB) pathway-associated proteins (p-p65, p65), were evaluated using ELISA and Western blotting. TTC staining was performed to determine infarct size, while neurological deficits were scored with the modified neurological severity score (mNSS). For the in vitro study, BV2 microglial cells were subjected to oxygen-glucose deprivation/reperfusion (OGD/R) and allocated to four groups: Control, OGD, OGD+LPC, and OGD+LPC+BAY 11-7082. The concentrations of inflammatory mediators in the culture supernatant were measured using ELISA, and the expression of NF-κB pathway-related proteins was examined by Western blotting.Results: In the in vivo study, relative to Sham controls, the MCAO group exhibited markedly elevated brain LPC concentrations and reduced serum LPC levels (p < 0.05). Tissue and serum contents of TNF-α, IL-1β, and IL-6 were also significantly increased in the MCAO group (p < 0.05), along with a higher p-p65/p65 ratio in brain tissue (p < 0.05). Moreover, infarct size and mNSS scores were significantly augmented (p < 0.05). These observations suggest elevated brain LPC levels are accompanied by increased neuroinflammation and NF-κB pathway activation in the MCAO model. In the cell-based experiments, OGD/R exposure led to significant elevations in supernatant TNF-α, IL-1β, and IL-6 levels and in the p-p65/p65 ratio versus the Control group (p < 0.05). Addition of LPC further increased these parameters in OGD/R-treated cells (p < 0.05), whereas co-treatment with BAY 11-7082 significantly reversed these effects (p < 0.05).Conclusion: In vitro findings suggest that LPC can promote the expression of inflammatory factors in microglia following ischemic stroke, potentially through activating the NF-κB signaling pathway. While in vivo data show a correlation between elevated brain LPC levels and post-stroke inflammation, further studies with direct LPC intervention are required. The LPC-NF-κB axis may represent a candidate pathway for future therapeutic investigation.