Robust FoxO3 expression localized differentially to the cytoplasm of astrocytes and nuclei of Olig2⁺ oligodendroglia in chronic human WMI. (A) Left: Low-power image of preterm WMI (Supplemental Table 1A; case 3). Diffuse FoxO3 staining defined boundaries of this large lesion between the cortical mantle (arrowheads) and the lateral ventricle (not shown). Middle: Rare FoxO3-labeled cells (red arrowheads) in normal-appearing WM adjacent to the lesion. Right: FoxO3 localized to numerous reactive astrocytes (red arrowheads) and nuclei (black arrowheads) in the lesion. (B) FoxO3 expression in a chronic active MS plaque (Supplemental Table 1B; case 1). Left: Low-power image of a chronic active plaque stained for FoxO3 and MBP with markedly reduced MBP staining in the core versus the peri-plaque. Middle: Detail of the plaque edge shows scattered MBP-labeled myelin debris (brown) and numerous FoxO3-labeled nuclei (black arrowheads). Right: Within the plaque core, no myelination was visualized, but many FoxO3-labeled nuclei (black arrowheads) were interspersed among reactive astrocytes (red arrowheads). (C) FoxO3 expression in an active remodeling MS plaque (Supplemental Table 1B; case 1). Left: Low-power image of the plaque stained for FoxO3 and MBP with scattered islands of remyelination within the lesion. Middle: Numerous FoxO3-labeled nuclei (black arrowheads) localized among sparsely myelinated axons (brown). Right: A heavily myelinated peri-plaque region with rare FoxO3-labeled nuclei (black arrowheads). (D) FoxO3-labeled nuclei in a preterm WM lesion (Supplemental Table 1A; case 1) and MS plaques (Supplemental Table 1B; case 3) colocalized with the pan OL lineage marker Olig2. Colocalization of Olig2 fluorescence and FoxO3 colorimetric labeling is indicated in the merge in red. Scale bars: 200 μm, A, left; 20 μm, A, middle and right; 300 μm, B, left; 20 μm, B and C, middle and right; 300 μm, C, left; 30 μm, D.