What causes cerebral malaria?
The cause of cerebral malaria is not well understood. Currently, there are two major hypotheses explaining its etiology. They are the mechanical and the humoral hypotheses. The mechanical hypothesis asserts that a specific interaction between a P. falciparum erythrocyte membrane protein (PfEMP-1) and ligands on endothelial cells, such as ICAM-1 or E-selectin, reduces microvascular blood flow and induces hypoxia. This selective cytoadherence of PRBCs and non-PRBCs, also known as rosetting, can apparently better account for CM’s histopathological hallmark and its characteristic coma condition. However, this hypothesis is inadequate in explaining the relative absence of neurological deficit even after days of unconsciousness. The humoral hypothesis suggests that a malarial toxin may be released that stimulates macrophages to release TNF-a and other cytokines such as IL-1. The cytokines themselves are not harmful, but they may induce additional and uncontrolled production of nitric oxide.
