Mouse NOD/Shi and NSY/Hos strains infected with <i>Plasmodium berghei</i> ANKA are models for experimental cerebral malaria

In humans, cerebral malaria is the most common cause of malaria-related mortality. Mouse C57BL/6 (B6) sub-strains are the major model system for experimental cerebral malaria (ECM) as they show similar pathophysiology to human cerebral malaria after infection with the rodent malaria parasite Plasmodium berghei ANKA. This model system has been used to analyze the molecular mechanisms of cerebral malaria. To develop new mouse models, we analyzed the ECM susceptibility of NOD/Shi (NOD) and NSY/Hos (NSY) strains established from the non-inbred ICR strain. Both NOD and NSY strains exhibited clinical symptoms and pathologies similar to ECM in C57BL/6J (B6J) mice and died within 11 days of infection. Thus, the NOD and NSY strains are susceptible to ECM and may be useful as new ECM models. The ECM susceptibility of both strains is suggested to be due to homozygosity for the cerebral malaria susceptibility allele of the ECM susceptible ICR strain. Although analyses using B6 sub-strains have proposed that complement component 5 (C5) plays an important role in ECM pathogenesis, we found that C5 was not essential as the ECM susceptible NOD strain is C5 deficient. Thus, results obtained from B6 sub-strains may not reflect the full picture of ECM in mice. Comparative analyses of multiple ECM models will contribute to a more accurate identification of the factors essential for ECM.