We previously found that monocyte locomotion inhibitory factor has a neuroprotective effect on ischemic brain injury during the acute phase of stro ke.Therefore,we modified the structure of an anti-inflammato ry monoc...We previously found that monocyte locomotion inhibitory factor has a neuroprotective effect on ischemic brain injury during the acute phase of stro ke.Therefore,we modified the structure of an anti-inflammato ry monocyte locomotion inhibitory factor peptide to construct an active cyclic peptide—Cyclo(MQCNS)(LZ-3)—and investigated its effects on ischemic stroke.In this study,we established a rat model of ischemic stroke by occluding the middle cerebral artery and then administered LZ-3(2 or 4 mg/kg) via the tail vein for 7 consecutive days.Our res ults showed that LZ-3(2 or 4 mg/kg) substantially decreased infarct volu m e,reduced co rtical ne rve cell death,improved neurological function,reduced cortical and hippocampal injury,and decreased the levels of inflammatory factors in the blood and brain tissues.In a well-diffe rentiated,oxygen-glucose deprivation/reoxygenation-induced BV2 cell model of poststroke,LZ-3(100 μM) inhibited the JAK1-STAT6 signaling pathway.LZ-3 regulated microglia/macrophage polarization from the M1 to the M2 type and inhibited microglia/macrophage phagocytosis and migration via the JAK1/STAT6 signaling pathway.To conclude,LZ-3 regulates microglial activation by inhibiting the JAK1/STAT6 sign aling pathway and improves functional recovery post-stroke.展开更多
文摘We previously found that monocyte locomotion inhibitory factor has a neuroprotective effect on ischemic brain injury during the acute phase of stro ke.Therefore,we modified the structure of an anti-inflammato ry monocyte locomotion inhibitory factor peptide to construct an active cyclic peptide—Cyclo(MQCNS)(LZ-3)—and investigated its effects on ischemic stroke.In this study,we established a rat model of ischemic stroke by occluding the middle cerebral artery and then administered LZ-3(2 or 4 mg/kg) via the tail vein for 7 consecutive days.Our res ults showed that LZ-3(2 or 4 mg/kg) substantially decreased infarct volu m e,reduced co rtical ne rve cell death,improved neurological function,reduced cortical and hippocampal injury,and decreased the levels of inflammatory factors in the blood and brain tissues.In a well-diffe rentiated,oxygen-glucose deprivation/reoxygenation-induced BV2 cell model of poststroke,LZ-3(100 μM) inhibited the JAK1-STAT6 signaling pathway.LZ-3 regulated microglia/macrophage polarization from the M1 to the M2 type and inhibited microglia/macrophage phagocytosis and migration via the JAK1/STAT6 signaling pathway.To conclude,LZ-3 regulates microglial activation by inhibiting the JAK1/STAT6 sign aling pathway and improves functional recovery post-stroke.
