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Accumulating evidence has demonstrated the involvement of B cells in neuroinflammation and neuroregeneration. However, the role of B cells in ischemic stroke remains unclear. In this study, we identified a novel phenotype of macrophage-like B cells in brain-infiltrating immune cells expressing a high level of CD45. Macrophage-like B cells characterized by co-expression of B-cell and macrophage markers, showed stronger phagocytic and chemotactic functions compared with other B cells and showed upregulated expression of phagocytosis-related genes. Gene Ontology analysis found that the expression of genes associated with phagocytosis, including phagosome- and lysosome-related genes, was upregulated in macrophage-like B cells. The phagocytic activity of macrophage-like B cells was verified by immunostaining and three-dimensional reconstruction, in which TREM2-labeled macrophage-like B cells enwrapped and internalized myelin debris after cerebral ischemia. Cell-cell interaction analysis revealed that macrophage-like B cells released multiple chemokines to recruit peripheral immune cells mainly via CCL pathways. Single-cell RNA sequencing showed that the transdifferentiation to macrophage-like B cells may be induced by specific upregulation of the transcription factor CEBP family to the myeloid lineage and/or by downregulation of the transcription factor Pax5 to the lymphoid lineage. Furthermore, this distinct B cell phenotype was detected in brain tissues from mice or patients with traumatic brain injury, Alzheimer’s disease, and glioblastoma. Overall, these results provide a new perspective on the phagocytic capability and chemotactic function of B cells in the ischemic brain. These cells may serve as an immunotherapeutic target for regulating the immune response of ischemic stroke.

Objective: To evaluate the efficacy and safety of tirofiban for patients with acute ischemic stroke (AIS), especially posterior circulation stroke (PCS).Methods: We enrolled consecutive patients with AIS who suffered large artery occlusion (LAO) and underwent mechanical thrombectomy (MT) between January 2016 and May 2020. Patients were divided into two groups according to whether tirofiban was used during MT. The primary efficacy outcome was a favorable functional outcome, defined as a modified Rankin Scale (mRS) score of 0–2 at 3 months. The safety outcomes were the rate of mortality at 3 months and the presence of intracranial hemorrhage (ICH) and symptomatic intracranial hemorrhage (sICH). Cohorts were balanced using 1:1 propensity score matching (PSM). Subgroup analysis was further performed to compare the efficacy and safety of tirofiban between the anterior circulation stroke (ACS) and PCS groups.Results: A total of 292 patients were eligible for this study and divided into the tirofiban group (n = 51) and the no-tirofiban group (n = 241). In the propensity-score-matched cohort, the tirofiban group had a higher rate of favorable outcomes than the no-tirofiban group (49.0 vs. 25.5%, p = 0.014), and the mortality at 3 months showed a greater downward trend in the tirofiban group than the no-tirofiban group (15.6 vs. 33.3% p = 0.064). The risk of sICH and ICH was the same between the tirofiban and control groups (17.6 vs. 27.4% p = 0.236, 31.3 vs. 45.1% p = 0.154, respectively). Tirofiban use was predictive of favorable outcomes [adjusted odds ratio (aOR) = 2.87, 95% confidence interval (CI) 1.52–6.44, p = 0.043] after multiple logistic regression analysis. Subgroup analysis revealed that tirofiban use was significantly associated with favorable outcomes in ACS (aOR = 3.66, 95% CI 1.24–5.22, p = 0.019) but not in PCS (aOR = 1.12, 95% CI 0.47–7.52, p = 0.570).Conclusion: We demonstrated that tirofiban may be associated with improving favorable outcome for the AIS patients who underwent MT, without increasing ICH or sICH. Furthermore, our results indicated that for PCS patients tirofiban may not be associated with favorable outcome, and more comprehensive randomized controlled trials are needed to confirm this finding.