Fig. 8

Hypoxia-induced TJ disruption is rescued by pericyte-targeted HIF-1 deletion. Representative images of SMMHC-CreER^T2; HIF-1α^fl/fl Ctrl and LoF brain sections co-immunostained for junctional proteins (A) ZO-1 or (B) claudin-5 (green, Z-stack images) with CD31 (red), from mice exposed to 96 h normoxia (Nx) and hypoxia (Hx, 8% O₂). Nuclei are counterstained with DAPI (blue). Arrowheads highlight loss of TJ staining within microvessels. Scale bars = 100 µm and 25 µm, respectively. Quantification of ZO-1 (C) and claudin-5 (D) staining in brain cortical regions of HIF-1 Ctrl and LoF mice during normoxia and hypoxia. Two-way ANOVA, mean ± SD, n = 3–4, *p < 0.05 compared to Nx Ctrl, δp < 0.05 compared to Hx Ctrl. E Representative microvessel electron microscopy images from SMMHC-CreER^T2; HIF-1α^fl/fl mice exposed to different conditions showing tight junction arrangement between adjacent endothelial cells. Astrocytes (AC) are indicated in blue font, pericytes (PC) in yellow and endothelial cells (EC) in green font. Insets highlight intact (arrow) or disrupted (arrowhead) TJ structures at endothelial cell borders. Scale bar = 0.5 µm