Fig. 5

Graphical abstract of the mouse pial vascular network after infection with P. Berghei / ANKA. a. Progression of cerebral malarial in the rodent model. Neurological and motor dysfunction correlate with reduced cerebral blood flow and increased inflammation. b. Balance between pro-oxidant and anti-oxidant determines survival of erythrocytes. Limiting the capacity to deal with oxidative stress by inhibiting G6PD and limiting NADPH levels with RRx-001, increases efficacy of anti-malarial therapies. Intraerythrocytic malarial parasites are subject to high levels of free radicals due to the catabolism of Hb. Additional RONS stress from RRx-001 and artemether may tip the parasite over the threshold into death. c. Macroscopic images of cranial windows from the rodent model. Images are from day 9 after infection. Uninfected animals show normal microcirculation. Artemether treated animal showed micro-haemorrhages. RRx-001 treated animal showed preserved microcirculation structure. Artemether and RRx-001 treated animal showed preserved microcirculation structure and microvascular function. Untreated animals showed micro-haemorrhages followed by vasospasms