Role of Apoptosis in Cerebral Malaria

摘要

We hypothesized that cerebral malaria (CM)-induced apoptosis in brain vascular endothelial cells mediates blood brain barrier (BBB) dysfunction. Therefore, abrogation of key host death receptors will reduce pathology and increase survival. Parasite-induced changes in apoptotic gene and protein expression in P, berghei ANKA (PBA)-infected and uninfected mouse brain was evaluated. Human brain vascular endothelial cells (HBVEC) exposed to infected or uninfected erythrocytes conditioned media were assayed by TUNEL. Caspase-3 expression was upregulated in infected mouse brains but was unchanged in uninfected controls. PBA-IRBC-conditioned medium induced apoptosis in HBVEC than unconditioned medium. Infected Fas-/-, TNFR1-/-, and TNFR2-/- mice survived longer than wild-type C57BL/6J. Thus, CM pathology may be mediated by apoptosis.