Immunopathology of cerebral malaria: Morphological evidence of parasite sequestration in murine brain microvasculature

A murine model that closely resembles human cerebral malaria is presented, in which characteristic features of parasite sequestration and inflammation in the brain are clearly demonstrable. "Young" (BALB/c x C57BL/6)F-1 mice infected with Plasmodium berghei (ANKA) developed typical neurological symp toms 7 to 8 days later and then died, although their parasitemias were belo w 20%. Older animals were less susceptible. Immunohistopathology and ultras tructure demonstrated that neurological symptoms were associated with seque stration of both parasitized erythrocytes and leukocytes and with clogging and rupture of vessels in both cerebral and cerebellar regions. Increases i n tumor necrosis factor alpha and CD54 expression were also present. Simila r phenomena were absent or substantially reduced in older infected but asym ptomatic animals. These findings suggest that this murine model is suitable both for determining precise pathogenetic features of the cerebral form of the disease and for evaluating circumventive interventions.