Model for ECM-associated vascular leakage.

<p><b>(A)</b> 1) Arrested Schizont ruptures in the cerebral capillary releasing merozoites. 2) pRBC-dependent alterations in cerebral capillary blood flow facilitate EC phagocytosis of merozoites and digestive vacuoles. 3) ECs cross-present parasite antigen on MHC class I molecules to CD8⁺ T-cells. 4) CD8⁺ T-cells degranulate and release cytotoxic perforin and granzyme molecules). 5) The cytolytic molecules induce apoptosis signalling within the target EC. <b>(B)</b> 1) Target EC induces anti-apoptosis signalling pathways to counteract cytolysis via 2) the secretion of growth factors. Growth factors act in an autocrine fashion on the target EC and 3) paracrine fashion on neighbouring ECs. This results in: 4a) the upregulation of caveolae within affected ECs; and 4b) alterations to intercellular EC tight junctions. 5) The enhanced permeability of the cerebrovasculature leads to enlargement of the perivascular spaces and formation of oedematous parenchymal tissue, which precipitate fatal increases in intracranial pressure.