Complement C5-deficient mice are protected from seizures in experimental cerebral malaria.

Studies have demonstrated that the membrane attack complex (MAC) of complement can evoke seizures when injected directly into rodent brain. In the course of studies that examine the role of complement in the development of experimental cerebral malaria (ECM), we observed fewer seizures in mice deficient in C5, a component required for MAC formation. To determine if the MAC contributed to the tonic-clonic seizures characteristic of ECM, we performed long-term video-electroencephalography (EEG) on C5(-/-) mice with Plasmodium berghei ANKA-induced cerebral malaria and observed significantly reduced spike and seizure frequency compared to wild-type mice. Our data suggest a role for the MAC in malaria-induced seizures and that inhibition of the terminal complement pathway may reduce seizures and seizure-related neurocognitive deficits. Wiley Periodicals, Inc.