van der Heyde Henri C, Nolan John, Combes Valéry, Gramaglia Irene, Grau Georges E
La Jolla Bioengineering Institute, La Jolla, CA 92037, USA.
Trends Parasitol. 2006 Nov;22(11):503-8. doi: 10.1016/j.pt.2006.09.002. Epub 2006 Sep 18.
A unifying hypothesis for the genesis of cerebral malaria proposes that parasite antigens (released by replication in blood, surface molecules on parasitized erythrocytes, or merozoites) activate platelets that, in turn, contribute to the activation of the inflammatory response and increased levels of endothelial cell adhesion molecules (eCAMs). Increased levels of eCAMs result in further parasitized-erythrocyte sequestration and marked local inflammation that might disrupt the brain microvasculature, which cannot be repaired by the hemostasis system because of its procoagulant state. Disruption of the brain microvasculature can result in vascular leak and/or hemorrhaging into the brain; similar processes can occur in other vascular beds, including the lung. The blockage of functional capillaries by parasitized and/or unparasitized erythrocytes with decreased deformability or rosettes is also a key interaction between hemostasis and mechanical obstruction leading to pathogenesis. The events resulting in the development of cerebral malaria complications are multi-factorial, encompassing a dynamic interaction between three processes, thereby explaining the complexity of this deadly syndrome.
关于脑型疟疾发病机制的一个统一假说提出，寄生虫抗原（通过在血液中复制释放、寄生红细胞表面分子或裂殖子）激活血小板，进而促进炎症反应的激活以及内皮细胞黏附分子（eCAMs）水平的升高。eCAMs水平升高导致更多寄生红细胞的滞留以及明显的局部炎症，这可能会破坏脑微血管，由于其促凝状态，止血系统无法对其进行修复。脑微血管的破坏可导致血管渗漏和/或脑出血；类似的过程也可能发生在包括肺在内的其他血管床。变形能力降低的寄生和/或未寄生红细胞或玫瑰花结对功能性毛细血管的阻塞也是导致发病的止血与机械性阻塞之间的关键相互作用。导致脑型疟疾并发症发生的事件是多因素的，包括三个过程之间的动态相互作用，从而解释了这种致命综合征的复杂性。
