Mechanisms underlying brain metabolic changes in cerebral malaria.

每年约有200万人死于疟疾感染并发症。这些致命并发症中最常见的形式称为脑型疟疾。由于不完全理解的原因，患者的大脑受到影响。早期症状是行为改变，发展到昏迷。大约20%的疟疾感染昏迷患者死亡，其余患者康复，有时伴有轻微的神经损伤。在脑型疟疾发作期间，大脑处理糖的方式，为了使大脑功能所需的能量发生变化。它采取了一种模式，就像大脑缺氧一样，尽管这种情况是否真的发生还不清楚。另一种观点认为，这种脑生化变化是由细胞因子引起的。这些是免疫系统产生的蛋白质分子，作为攻击疟原虫的一部分。不幸的是，已知其中一些过量，特别是称为肿瘤坏死因子的因子，可能对宿主（在这种情况下，人类）产生有害影响。使用小鼠实验模型，我们将找出两种可能性（缺氧，细胞因子过度刺激）中的哪一种是脑型疟疾脑中生化变化的原因。这一点很重要，因为大脑很容易受到产生正常运作所需能量的通路变化的影响。通过这项工作，我们希望找到更好的治疗脑型疟疾的方法。

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.