Mechanisms underlying brain metabolic changes in cerebral malaria.

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About 2 million people die each year from complications of malaria infection. The most common form of these fatal complications is called cerebral malaria. For reasons that are not fully understood, the brain of the patient becomes affected. Early symptoms are behavioural changes, progressing to coma. About 20% of people who enter coma with malaria infection die and the remainder recover, sometimes with slight neurological impairment. During the cerebral malaria attack, the way that the brain handles sugar, in order to make the energy needed for brain function, is changed. It adopts a pattern rather like a brain that has been starved of oxygen, though whether this actually occurs is not clear. An alternative idea is that this change in brain biochemistry is caused by cytokines. These are protein molecules produced by the immune system as part of the attack on the malaria parasite. Unfortunately, in excess it is known that some of them, particularly the one called tumour necrosis factor, can have deleterious effects on the host (in this case, human beings). Using an experimental model in mice, we will find out which of the two possibilities (lack of oxygen, over-stimulation by cytokines) is responsible for the biochemical changes in the brain in cerebral malaria. This is important because the brain is very susceptible to changes in the pathways that produce the energy needed for it to function properly. From this work we hope to find out better ways of treating cerebral malaria.