Mechanisms underlying brain metabolic changes in cerebral malaria.

脑型疟疾脑代谢变化的机制。

• 批准号: nhmrc : 107326
• 负责人: E/Pr Nicholas Hunt
• 金额: $ 22.28万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2000
• 资助国家: 澳大利亚
• 起止时间: 2000-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/mechanisms-underlying-brain-cerebral-malaria/98400
• 关键词: Mechanisms; underlying; brain; metabolic; changes

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.

每年约有200万人死于疟疾感染并发症。这些致命并发症最常见的形式被称为脑型疟疾。由于尚不完全清楚的原因，患者的大脑受到影响。早期症状是行为改变，发展为昏迷。大约20%因疟疾感染而进入昏迷状态的人死亡，其余人康复，有时伴有轻微的神经损伤。在脑疟疾发作期间，大脑处理糖的方式发生了变化，以产生大脑功能所需的能量。它采用的模式很像缺氧的大脑，尽管这种情况是否真的发生尚不清楚。另一种观点认为，大脑生物化学的这种变化是由细胞因子引起的。这些是免疫系统在攻击疟原虫过程中产生的蛋白质分子。不幸的是，众所周知，其中一些，特别是一种叫做肿瘤坏死因子的，如果过量，会对宿主（在这种情况下，对人类）产生有害影响。通过对小鼠的实验模型，我们将发现两种可能性（缺氧，细胞因子的过度刺激）中哪一种是脑型疟疾中大脑生化变化的原因。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途径变化的影响。通过这项工作，我们希望找到更好的治疗脑疟疾的方法。