Vascular leakage is associated with dysregulation of transcellular and paracellular transport mechanisms during ECM.

<p>C57BL/6 mice were infected with 1x10⁴ <i>Pb</i> ANKA GFP (n = 3) or 1x10⁴ <i>Pb</i> NK65 GFP (n = 3) pRBCs. Mice were culled at d7 p.i when <i>Pb</i> ANKA infected mice exhibited signs of late-stage ECM. Brains were removed from transcardially perfused mice and processed for TEM <b>(A)</b> Electron micrographs of representative vessels from <i>Pb</i> ANKA and <i>Pb</i> NK65 infected mice. Note the thickened endothelium and narrowed lumen consistent with vasospasm, cytoplasmic extensions and extensive caveolae seen during <i>Pb</i> ANKA infection. <b>(i and ii)</b> Digitally magnified panels showing endothelial cytoplasmic extensions and extensive caveolae (▲) specifically during <i>Pb</i> ANKA infection. The potential mechanisms of microvessel leakage during <i>Pb</i> ANKA infection include: <b>(B)</b> transendothelial channel (▲); <b>(C)</b> vacuolar cleft (▲) associated with an endothelial cell tight junction, numerous caveolae adjacent; <b>(D)</b> cleft (▲) in an atypical endothelial cell tight junction; <b>(E)</b> cleft within microvascular tight junction (▲) adjacent to fluid accumulation within the perivascular space (◊); <b>(F)</b> caveolae (▲) proximal to astrocyte end-feet swelling (◊), extravasated RBCs (*) can also be visualised. Scale bars: A, E & F 1μm; B-D 2μm.