Basp1 Intensifies Neutrophil Migration and NETs Formation in Traumatic Brain Injury

Brain abundant membrane attached signal protein 1 (Basp1), a member of the neuronal growth-associated protein family, was originally identified for its high expression in the central nervous system. Recent evidence suggests its involvement in peripheral diseases through modulation of myeloid cell function; however, the molecular mechanisms remain poorly defined. In this study, by re-analyzing single-cell RNA sequencing data from peripheral blood of TBI patients and validating results in a mouse TBI model via flow cytometry, we demonstrated that Basp1 was specifically upregulated in neutrophils after injury. Using tamoxifen-induced lineage tracing (Basp1⁺-TdTomato⁺), we further confirmed that Basp1-expressing neutrophils represented the majority of infiltrated neutrophils in the brain during acute TBI. Bulk RNA-seq comparing Basp1⁺ and Basp1^- neutrophils revealed Basp1's central role in regulating neutrophil migration and neutrophil extracellular traps (NETs) formation. Silencing Basp1 impaired both processes in vitro, and real-time PCR analysis indicated correlated downregulation of key chemotaxis-related (Itgb2, Cybb, Mmp9, Actn1, Cxcr2, Pik3cb) and NETs-related genes (Fcgr1, H3c1, Tlr2). Protein docking and co-immunoprecipitation assays demonstrated a direct interaction between Basp1 and Vimentin in neutrophils, suggesting a mechanism by which Basp1 promotes cytoskeletal rearrangement essential for migration and NETs formation. Notably, conditional KO Basp1 in myeloid cells significantly reduced neutrophil infiltration and NETs formation after TBI. Our work identifies Basp1 as a critical molecular mediator of neutrophil-driven inflammation in TBI, providing a potential therapeutic target not only for TBI but also for other neuroinflammatory conditions.