| First Author | Nakisli S | Year | 2025 |
| Journal | Sci Rep | Volume | 15 |
| Issue | 1 | Pages | 3932 |
| PubMed ID | 39890825 | Mgi Jnum | J:369484 |
| Mgi Id | MGI:7860521 | Doi | 10.1038/s41598-025-86150-4 |
| Citation | Nakisli S, et al. (2025) CNS resident macrophages exhibit region-specific states and immunogenic responses during Rbpj-deficient brain arteriovenous malformation. Sci Rep 15(1):3932 |
| abstractText | Microglia are heterogeneous macrophage cells that serve as the central nervous system's resident immune cells. During neuro-related diseases, CNS resident macrophages change their molecular, cellular, and functional properties-that collectively define "states"-in response to specific neural perturbations. Neurovascular diseases elicit state changes, by promoting increased vascular permeability among microvessels and thus altering blood-brain barrier integrity. Here, we used a mouse model of brain arteriovenous malformation (bAVM)-mediated by endothelial loss of Recombination signal binding protein for immunoglobulin kappa J region (Rbpj)-to investigate changes to brain resident macrophage states during neurovascular disease pathogenesis. We found increased area of Ionized calcium-binding adapter molecule 1 (Iba1) expression in Rbpj-deficient bAVM tissue, as well as Iba1 + cell hypertrophy, increased cell number, and hyperproliferation within areas of increased Iba1 + density. Hypertrophic cells had increased cell body areas and decreased process length, suggesting a transition in surveillance state. Gene expression data revealed region-specific molecular changes to Iba + cells, suggestive of altered metabolic activity. CNS resident macrophages isolated from cortical and cerebellar regions showed profiles consistent with cytokine-associated immunogenic responses and an immunovigilant pathogen-recognition response, respectively. Thus, our findings demonstrate region-specific changes to CNS resident macrophages during Rbpj-deficient bAVM. |
