Scanning electron microscopy of the neuropathology of murine cerebral malaria

C57BL/6J mice were infected with Plasmodium berghei ANKA blood stages. When typical symptoms of CM developed perfused brains were processed for SEM or light microscopy, respectively.Ultrastructural hallmarks were disruption of vessel walls, parenchymal haemorrhage, leukocyte sequestration to the endothelium, and diapedesis of macrophages and lymphocytes into the Virchow-Robin space. Villous appearance of observed lymphocytes were indicative of activated state. Cerebral oedema was evidenced by enlargement of perivascular spaces.The results of the present study corroborate the current understanding of CM pathophysiology, further support the prominent role of the local immune system in the neuropathology of CM and might expose new perspectives for further interventional studies.Cerebral malaria (CM) is a major cause of mortality and morbidity in severe Plasmodium falciparum malaria. Frequently seen neurological dysfunctions are delirium, convulsions, coma and eventual death if the disease is not controlled. Post mortem analyses of brains of CM patients show adherence of parasitized red blood cells (pRBC) and inflammatory cells to the microvasculature of the brain, parenchymal microhaemorrhages and oedema. The pathophysiological mechanisms of CM are still discussed controversially. However, most researchers agree that two main factors contribute to the development of CM. On the one hand sequestration of blood cells (i.e. pRBC, leukocytes and thrombocytes) on activated endothelia causes obstruction of microvascular flow leading to local hypoxia [1,2]. On the other hand, excessively elevated cytokines in serum lead to activation of brain resident microglial cells which trigger local inflammatory processes [3-5]. Most of the knowledge about the pathophysiological mechanisms originates from studies in animal models (i.e. rodents) since the early stages of the disease are neuropathologically not addressable in humans. Hence the histopathology of murine CM has been studied in