Figure 1

Most commonly accepted hypotheses for pathophysiological mechanisms underlying clinical progress towards cerebral malaria (CM). The diagram summarizes the three distinct hypotheses on CM etiology and their typical features: i) the mechanical hypothesis is associated with iRBC cytoadherence and their reduced deformability, causing following anemia, rosette formation and microvascular obstruction; ii) the permeability hypothesis is based on BBB impairment and subsequent increase in vascular permeability, allowing toxic compounds to reach the brain parenchyma and causing neurological dysfunction; iii) the humoral hypothesis focuses on the enhanced production by the host of pro-inflammatory molecules, including cytokines and chemokines, and other soluble factors such as ROS, which are putatively responsible for inflammation, fever and coma during CM.