Astrocytic expression of IL-17A induces a vascular pathology with capillary calcifications, microvascular rarefaction and thickening of endothelial layer and basement membrane of vessel walls without disturbing blood-brain barrier integrity.

<p>GFAP immunohistochemistry (<b>A–B</b>), lectin (<b>C</b>) and Alizarin red S staining (<b>D</b>) of the thalamus in WT mice (<b>A</b>) and GF/IL17 transgenic animals (<b>C–D</b>) at the age of 09 month. Microvessels surrounded by GFAP positive astrocytic endfeet and laminin stained endothelia are filled with hematoxillin positive material (white arrows). Around calcified microvessels astrocytes display an activated morphology. Deposits are labelled orange/red in Alizarin red S staining (<b>D</b>) confirming vascular calcifications. Transmission electron microscopy of capillaries in the corpus callosum of (<b>E</b>) wild-type mice and (<b>F</b>) GF/IL17 transgenic mice at the age between 10 and 12 month exhibit morphological criteria of microangiopathy: the endothelial cell layer <i>(Endo)</i> appears enlarged compared with WT. Basement membrane <i>(red-colorored)</i> surrounding the vascular endothelium appears heavily thickened in TG animals. GF/IL17 mice display numerous duplications of the basement membrane spanning the perivascular space harbouring pericytes <i>(green colored)</i>. Inside capillaries erythrocytes <i>(Ery)</i> are detectable. Scale bar represents 1 µm. (<b>G</b>) Measurement of basement membrane thickness revealed a significant diameter increase in GF/IL17 mice (p < 0,05) (<b>H</b>) Confocal microscopy of 50 µm sections labelled with anti-laminin displayed a dense microvascular network in the white matter of WT animals. (<b>I</b>) Rarefaction of microvasculature in corresponding areas in GF/IL17 mice. Furthermore arterioles appear thickened. (Age: 10–12 month of both transgenic and wild-type mice) (<b>J</b>) To examine blood-brain barrier integrity Evans blue dye (EBD) extravasation into tissue was quantified. Levels of tissue EBD in brains and spinal cord are equal in WT and GF/IL17 mice. Liver tissue served as positive controls.