Department of Pathology, Vascular Immunology Unit, Sydney Medical School, The University of Sydney, Australia.
Prog Neurobiol. 2010 Jun;91(2):140-51. doi: 10.1016/j.pneurobio.2010.01.007. Epub 2010 Jan 29.
Cerebral malaria (CM) is still a major world health problem whose pathogenic mechanisms remain incompletely understood. After reviewing some particularities of anti-malarial immunity, we focus here on the neurovascular aspects of CM. We specifically address the central role of endothelial activation and alteration in disease pathogenesis. We discuss the respective roles of "mediator-induced" versus "host cell-induced" mechanisms of endothelial alteration. The former include cytokines, chemokines and their receptors, while the latter encompass cells located inside and outside the vessel, notably glial cells. We also present evidence for a pathogenic role for membrane microparticles (MP) in CM, based on studies in African patients and in a recognised mouse model. Intervention studies on MP production, via either gene knockout or pharmacological inhibition, can prevent the neurological syndrome and its associated mortality, suggesting potential new therapeutic avenues.
脑型疟疾（CM）仍然是一个主要的全球卫生问题，其发病机制仍不完全清楚。在回顾了抗疟免疫的一些特殊性之后，我们在这里重点关注 CM 的神经血管方面。我们特别讨论了内皮细胞激活和改变在疾病发病机制中的中心作用。我们讨论了“介质诱导”与“宿主细胞诱导”的内皮改变机制的各自作用。前者包括细胞因子、趋化因子及其受体，而后者包括血管内和血管外的细胞，特别是神经胶质细胞。我们还基于对非洲患者和公认的小鼠模型的研究，提出了膜微粒（MP）在 CM 发病机制中的致病作用的证据。通过基因敲除或药物抑制来干预 MP 的产生，可以预防神经系统综合征及其相关死亡率，这提示了新的潜在治疗途径。
