Fig. 5.

E6446 prevents breakdown of the BBB and neurological signs of malaria. (A) Each of the classic CM symptoms (ruffled fur, abnormal posture, unbalancing, limb paralysis, convulsion, coma, and death) was given a score (0, 2, 4, 8, or 10). Mice were then graphically ranked based on symptoms presented at each time point. Open and closed circles represent mice treated with either E6446 or vehicle. (B) After 7 d of infection, mice were injected i.v. with 0.2 mL of 1% Evans blue (Sigma–Aldrich) shortly before the death of vehicle-treated mice (120 mg·kg⁻¹·d⁻¹). One hour later, mice were killed and brain coloration was assessed. Naive mice were also injected with Evans blue and used as a control. (C) Brains from vehicle- or E6446-treated mice were harvested at day 7 postinfection and fixed in formalin; brain sections were then stained with H&E. Brain lesions were identified over oil immersion 1,000× magnification (Left) and counted over 40× magnification (Right) on an optical microscope. Statistical analysis was performed using an unpaired two-tailed Student's t test. A P value <0.05 was considered to be statistically significant.