Inhibition of CCL/CXCL signaling pathway-mediated neutrophil chemotaxis alleviates secondary brain injury after traumatic brain injury
LI Kailu
DONG Baowen
PENG Tao
MENG Jinyuan
FENG Dayun
Abstract：Objective To investigate the mechanisms underlying peripheral neutrophil central chemotaxis following traumatic brain injury(TBI)and its role in secondary brain injury.Methods Tissue samples from cortical lesions of TBI mice were dynamically collected at 6,12,24,48,and 72 h in the acute stage after TBI.RNA sequencing(RNA-seq)was used to analyze the dynamic changes of gene expression after TBI and the correlation with chemotaxis of peripheral immune cells.Primary neutrophils and TBI models were utilized to validate the role of CCL/CXCL signaling in neutrophil chemotaxis and neuroinflammation following TBI.Results The results of RNA-seq revealed significant upregulation over time of pathways related to leukocyte migration and cytokine-mediated inflammation after TBI.CCL/CXCL chemokine family genes as well as pro-inflammatory genes were upregulated across all time points.It was further confirmed that CCL3,CCL6,CCL9,CXCL2,and CXCL3 facilitated the recruitment of peripheral neutrophils into the central nervous system by acting on CCR1 and CXCR2 receptors,thereby activating inflammatory responses in neutrophils(P＜0.05,P＜0.01).Pharmacological inhibition of CCR1 and CXCR2 significantly mitigated neutrophil infiltration,microglial activation,and blood-brain barrier disruption in TBI mice.Conclusion The CCL/CXCL signaling pathway mediates the central chemotaxis of peripheral neutrophils following TBI,which can be used as an intervention target for secondary brain injury after TBI.
Keywords：traumatic brain injurysecondary brain injuryneutrophilsinflammatory responsechemotactic factor
Publication Date：2024-12-28
Online Publishing Date：2026-08-26(First online date of this platform, not the publication date of the document)
Pages：7( 1399-1405 )