Figure 1.

Proposed mechanism of vascular damage and BBB dysfunction in CM. The BBB is composed of ECs (orange), the basal lamina (purple), and astrocyte end feet (blue). Left panel: The vasculopathy in CM is likely a multifactorial process involving an up-regulation of the host inflammatory response. Interaction among PfRBCs, monocytes, and endothelial cells results in the up-regulation of proinflammatory cytokines, including TNF-α and IL-1β, which activates the cerebral endothelium. Middle panel: Additionally, there is recruitment and sequestration of iRBCs, monocytes, and platelets; this leads to mechanical occlusion and potentiates endothelial cell activation, and the up-regulation of cell adhesion molecules (CAMs) to which PfRBCs, immune cells, and platelets can adhere and thus obstruct the blood vessels and disrupt cerebral blood flow. Right panel: These two sets of events are thought to lead to BBB dysfunction. Cells of the BBB are damaged and undergo apoptosis; this allows entry of foreign materials into the brain parenchyma, creating hemorrhagic lesions and edema of the brain.