Spectrum of microvascular abnormalities observed in a focal model of type I IFN toxicity. A spectrum of microvascular disease is observed in mice with transgenic production type I IFN in the brain, across all anatomical regions. (A-C) Dose-dependent microvascular pathology in the hippocampus of transgenic mice with zero, low, and high levels of IFN overexpression (hematoxylin/eosin, abnormal small blood vessel highlighted by black arrow). (D) Dose-dependent microvascular pathology was observed across all major brain regions. ***P < .01, 1-way ANOVA for each region; n = 8 each group. (E-G) Perivascular inflammatory cell infiltration: hematoxylin/eosin (H+E), CD3, and CD31 immunohistochemistry shows small blood vessels with T-cell infiltration (CD3) and narrowing of lumen (CD31 endothelial marker). (H) Ectatic small vessel. (I) Perivascular infiltration by T cells (CD3, brown). (J) Intravascular calcification; bars represent 20 μm (E-G) and 40 μm (H, I). Scanning electron microscopy of microvascular cast shows multiple small capillary microaneurysms (K, blue arrow), large microaneurysm (L), and ectatic microvessel (M, blue arrow).