A role for Fas–Fas ligand interactions during the late-stage neuropathological processes of experimental cerebral malaria

Cerebral malaria (CM) kills more than 1 million children each year. Using a murine model of CM, we investigated the role of Fas–Fas ligand interactions in the neuropathogenesis of this disease. Lpr and Gld mice, deficient in Fas and Fas ligand, respectively, were protected from fatal CM, although they demonstrated some pathological features associated with CM in the wild type mouse. Fas–Fas ligand mRNA and protein expression were increased in the brain in mice with CM, and activated caspase-3-positive apoptotic astrocytes were observed. We suggest that Fas-mediated apoptosis of astrocytes is likely to be a critical factor in late-stage murine CM pathogenesis.