Mechanisms underlying brain metabolic changes in cerebral malaria.

每年约有200万人死于疟疾感染的并发症。这些致命并发症中最常见的形式被称为脑型疟疾。由于不完全了解的原因，患者的大脑会受到影响。早期症状是行为变化，进展到昏迷。感染疟疾进入昏迷状态的人中，约20%死亡，其余人康复，有时伴有轻微的神经损伤。在脑型疟疾发作期间，大脑处理糖的方式发生了变化，以制造大脑功能所需的能量。它采用的模式很像是缺氧的大脑，尽管这种情况是否真的发生还不清楚。另一种想法是，大脑生物化学的这种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，是攻击疟疾寄生虫的一部分。不幸的是，人们已经知道，其中一些化合物，特别是一种名为肿瘤坏死因子的物质，会对宿主(在这种情况下，是人类)产生有害影响。利用小鼠的实验模型，我们将找出两种可能性中的哪一种(缺氧，细胞因子过度刺激)导致脑型疟疾大脑的生化变化。这一点很重要，因为大脑非常容易受到产生正常运作所需能量的通路的变化的影响。从这项工作中，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.