ArticleFrontiers in cellular neuroscience2026
Single-cell transcriptomics identifies a putative perivascular macrophage-endothelial MIF-ACKR3 axis associated with endothelial activation in acute traumatic brain injury.
Article in Frontiers in cellular neuroscience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Blood-brain barrier (BBB) disruption is a hallmark of acute traumatic brain injury (TBI), yet the immune-vascular mechanisms underlying endothelial dysfunction remain incompletely understood. Perivascular macrophages (PVMs) are strategically positioned to modulate cerebrovascular homeostasis, but their role in acute post-traumatic endothelial activation has not been systematically characterized. Methods: We re-analyzed a publicly available mouse single-cell RNA sequencing (scRNA-seq) dataset (GSE290150, 24 h post-TBI) to characterize the landscape of immune and vascular cell populations and to infer intercellular communication. Bone marrow-derived macrophages (BMDMs) served as a PVM surrogate model, and bEnd.3 cerebral endothelial cells were used for Results: Single-cell analysis revealed concurrent expansion of PVM-like cells and activated endothelial cells (Activated ECs) in the TBI brain, with CellChat-predicted enhancement of MIF-ACKR3 signaling from PVM-like cells toward Activated ECs. Inflammatory stimulation of BMDMs significantly increased MIF expression and secretion in a STAT3-dependent manner. Macrophage-conditioned medium induced endothelial activation-associated molecular changes, including upregulation of Angpt2 and Adm and downregulation of tight junction genes Claudin5 and Tjp1; these effects were attenuated by MIF inhibitor ISO-1 or ACKR3 antagonist CCX771. Recombinant MIF dose-dependently reproduced these changes, which were substantially abrogated by ACKR3 pharmacological blockade or siRNA knockdown. STAT3 inhibition further suppressed rMIF-induced endothelial transcriptional responses. Conclusion: These findings provide transcriptomic and
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