Abstract:

Cerebral malaria is one of the major fatal complications of Plasmodium falciparum infection, and the pathogenesis is not fully understood. However, most of the current studies believe that the main pathogenesis of cerebral malaria is the obstruction of cerebral microcirculation caused by infected red blood cells adhering to cerebrovascular endothelial cells and the resulting immunopathological damage caused by the activation of cerebrovascular endothelial cells and the infiltration of inflammatory cells, which synergistically result in the disruption of blood-brain barrier and brain edema. Therefore, the magnitude of immune activation and damage to the cerebrovascular endothelial cells is one of the key factors in determining the progression and outcome of cerebral malaria. Existing clinical studies have proved that even active and effective anti-malarial treatment with artemisinin-based drugs cannot completely alleviate the celebral malaria symptoms and the possible subsequent neurological tissue damage, while the combination with anti-inflammatory treatment of glucocorticoids may cause serious side effects. The study on combination therapies of cerebral malaria involves multiple links for relevant pathogenesis, while the existing adjunctive therapies have not achieved the expected curative effect due to various factors, such as the complex life cycle and high antigenic variation of P. falciparum. Therefore, new combination therapies are urgently needed. This paper provides a brief review of the current progress in combination therapies against cerebral malaria with the target of protecting cerebrovascular endothelial cells by enhancing the self-protection function of endothelial cells and inhibiting the damage of other inflammatory cells or harmful factors to endothelial cells.

Key words: Cerebral malaria, Vascular endothelial cell, Adjunctive therapy