Defining the parasitological and immunological basis of cerebral pathology during murine experimental cerebral malaria

Cerebral malaria (CM) is a severe complication of some human malaria infections. CM is believed to be caused by the sticking (sequestration) of malaria-infected red blood cells and/or specific types of immune cells (white blood cells) in the small blood vessels of the brain. These blood vessels become clogged, blood flow is reduced and the lack of oxygen and other nutrients causes the patient to go into a coma or to have fits. In order to prevent or treat cases of CM, we need a better understanding of the cellular and molecular processes that lead to sequestration of red and white blood cells in the brain. It is impossible to carry out these studies in human malaria patients, but a clinically similar syndrome (experimental CM; ECM) develops in mice infected with particular strains of rodent malaria parasites. Even so, until now, it has been impossible to visualise the key events leading up to ECM in an intact mouse brain. I propose to use novel microscopic imaging techniques to visualise the migration, localisation and consequences of parasite and immune cell sequestration in the brains of infected mice and to identify the key molecules and cells involved in development of ECM.