Fig. 6

Rapamycin reduces brain pathology. a Luciferase activity and Pb18S expression indicative of luciferase-transgenic parasite accumulation in the brain of perfused mice (n = 5/group) on day 6 of infection treated on day 4 with vehicle (V) or rapamycin (R, 5 mg/kg) as indicated. b Quantitation of Evan’s blue dye in brains and photographs of representative brains from mice (n = 4–5/group) treated with vehicle or rapamycin (5 mg/kg) on day 4 and injected with Evan’s blue dye on day 6 after infection to assess blood–brain barrier function. c Representative micrographs of brains from vehicle and rapamycin treated (5 mg/kg) mice 6 days after malaria infection. Upper panels show representative images of the thalamic area, which presents disperse micro and macro-haemorrhages (arrows) scattered throughout the parenchyma. It is also evident in this image the vascular leukostasis (Inset), caused by clustering of leukocytes and infected RBCs (arrow head) within the blood vessels. Mid panels show representative images of the hypothalamus region presenting leukostasis and scattered micro-haemorrhages (arrows), defined as haemorrhagic areas smaller than 2 μm² (Inset). Lower panels show representative images comparing the cerebellum of vehicle and rapamycin treated mice. Inset shows a macro-haemorrhage in the molecular layer. Macro-haemorrhages (arrows) were defined as haemorrhages exceeding 2 μm². Quantitation of total number of brain haemorrhages per field of view are shown. Morphometric analysis showing the surface area of haemorrhages in whole brain sections are also shown. Hemorrhages were divided in micro-haemorrhages (< 2 μm²) and macro-haemorrhages (> 2 μm²). Data represent the mean ± SEM of over 100 fields of view. Scale bar = 100 μm. Inlets are ×40 magnified images of the selected regions