Abstract
Cerebral ischemia-reperfusion (I/R) injury is a difficult point in the treatment of ischemic stroke. Lipocalin-2 (LCN2) and neutrophils play an important role in I/R injury. We explored the effect of anti-LCN2 antibody (LCN2mAb) and to further clarify the relationship between LCN2mAb and neutrophil polarization (N1/N2 neutrophils) in I/R injury. A mouse middle cerebral artery occlusion (MCAO) model was used to induce transient cerebral ischemia. LCN2mAb was administered 1h before MCAO; Anti-Ly6G was administered for 3d before MCAO. The expression of LCN2 and Ly6G was Measured by western blot. Infarct size,behavior and the blood-brain barrier (BBB) damage were assessed. The polarized N2 neutrophils were measured by western blot and Flow Cytometry. Using HL-60 as a cell model explores the role of LCN2mAb in the polarity transition of neutrophils. The expression of LCN2 and Ly6G in the brain at different time points reached a peak after I/R 24h and then gradually decreased. As demonstrated previously, LCN2mAb-treated mice had neuroprotective effects in cerebral infarction volume, behavior, and blood-brain barrier damage. The expression of Ly6G was not significantly different, but the expression of N2 neutrophils was increased. The expression of anti-inflammatory factor CD206 was significantly increased, and pro-inflammatory factor TNF-α was significantly reduced. Compared with mice treated with Anti-Ly6G, Anti-Ly6G-LCN2mAb combined treatment of I/R, there was no further improvement in behavior and pathology. Based on HL-60 as a cell model, N1-HL-60 cells were pretreated with LCN2mAb, and N2-HL-60 cells were significantly increased. LCN2 may affect the prognosis of ischemic stroke by mediating neutrophils polarization.
Lipocalin-2 may produce damaging effect after cerebral ischemia by inducing astrocytes classical activation
