Medana I M, Chaudhri G, Chan-Ling T, Hunt N H
Departments of Pathology and Anatomy/Histology, University of Sydney, New South Wales, Australia.
Immunol Cell Biol. 2001 Apr;79(2):101-20. doi: 10.1046/j.1440-1711.2001.00995.x.
Cerebral malaria (CM) is a major life-threatening complication of Plasmodium falciparum infection in humans, responsible for up to 2 million deaths annually. The mechanisms underlying the fatal cerebral complications are still not fully understood. Many theories exist on the aetiology of human CM. The sequestration hypo-thesis suggests that adherence of parasitized erythrocytes to the cerebral vasculature leads to obstruction of the microcirculation, anoxia or metabolic disturbances affecting brain function, resulting in coma. This mechanism alone seems insufficient to explain all the known features of CM. In this review we focus on another major school of thought, that CM is the result of an over-vigorous immune response originally evolved for the protection of the host. Evidence in support of this second hypothesis comes from studies in murine malaria models in which T cells, monocytes, adhesion molecules and cytokines, have been implicated in the development of the cerebral complications. Recent studies of human CM also indicate a role for the immune system in the neurological complications. However, it is likely that multiple mechanisms are involved in the induction of cerebral complications and both the presence of parasitized erythrocytes in the central nervous system (CNS) and immunopathological processes contribute to the pathogenesis of CM. Most studies examining immunopathological responses in CM have focused on reactions occurring primarily in the systemic circulation. However, these also do not fully account for the development of cerebral complications in CM. In this review we summarize results from human and mouse studies that demonstrate morphological and functional changes in the resident glial cells of the CNS. The degree of immune activation and degeneration of glial cells was shown to reflect the extent of neurological complications in murine cerebral malaria. From these results we highlight the need to consider the potentially important contribution within the CNS of glia and their secreted products, such as cytokines, in the development of human CM.
脑型疟疾（CM）是人类感染恶性疟原虫后一种主要的危及生命的并发症，每年导致多达200万人死亡。致命性脑并发症的潜在机制仍未完全明确。关于人类脑型疟疾的病因存在多种理论。隔离假说认为，被寄生的红细胞黏附于脑血管会导致微循环阻塞、缺氧或影响脑功能的代谢紊乱，进而引发昏迷。但仅这一机制似乎不足以解释脑型疟疾的所有已知特征。在本综述中，我们聚焦于另一个主要的思想流派，即脑型疟疾是原本为保护宿主而进化出的过度活跃免疫反应的结果。支持这一第二种假说的证据来自对鼠疟模型的研究，其中T细胞、单核细胞、黏附分子和细胞因子与脑并发症的发展有关。对人类脑型疟疾的最新研究也表明免疫系统在神经并发症中发挥作用。然而，脑并发症的诱发可能涉及多种机制，中枢神经系统（CNS）中被寄生红细胞的存在以及免疫病理过程都对脑型疟疾的发病机制有影响。大多数研究脑型疟疾免疫病理反应的都集中在主要发生在体循环中的反应。然而，这些也不能完全解释脑型疟疾中脑并发症的发展。在本综述中，我们总结了来自人类和小鼠研究的结果，这些结果表明中枢神经系统中驻留的神经胶质细胞存在形态和功能变化。神经胶质细胞的免疫激活程度和退化程度反映了鼠脑型疟疾中神经并发症的程度。从这些结果中，我们强调在人类脑型疟疾的发展过程中，需要考虑神经胶质细胞及其分泌产物（如细胞因子）在中枢神经系统内可能的重要作用。
