Defining the parasitological and immunological basis of cerebral pathology during murine experimental cerebral malaria

脑型疟疾（CM）是一些人类疟疾感染的严重并发症。CM据信是由感染疟疾的红细胞和/或特定类型的免疫细胞（白细胞）粘附（隔离）在脑小血管中引起的。这些血管阻塞，血流减少，缺氧和其他营养物质的缺乏会导致病人陷入昏迷或痉挛。为了预防或治疗CM病例，我们需要更好地了解导致大脑中红细胞和白细胞隔离的细胞和分子过程。在人类疟疾患者中进行这些研究是不可能的，但是在感染了特定啮齿动物疟疾寄生虫菌株的小鼠中出现了临床类似的综合征（实验性CM； ECM）。即便如此，到目前为止，还不可能在一个完整的老鼠大脑中可视化导致ECM的关键事件。我建议使用新的显微成像技术来观察感染小鼠大脑中寄生虫和免疫细胞隔离的迁移、定位和后果，并确定参与ECM发展的关键分子和细胞。

Cerebral malaria (CM) is a severe complication of some human malaria infections. CM is believed to be caused by the sticking (sequestration) of malaria-infected red blood cells and/or specific types of immune cells (white blood cells) in the small blood vessels of the brain. These blood vessels become clogged, blood flow is reduced and the lack of oxygen and other nutrients causes the patient to go into a coma or to have fits. In order to prevent or treat cases of CM, we need a better understanding of the cellular and molecular processes that lead to sequestration of red and white blood cells in the brain. It is impossible to carry out these studies in human malaria patients, but a clinically similar syndrome (experimental CM; ECM) develops in mice infected with particular strains of rodent malaria parasites. Even so, until now, it has been impossible to visualise the key events leading up to ECM in an intact mouse brain. I propose to use novel microscopic imaging techniques to visualise the migration, localisation and consequences of parasite and immune cell sequestration in the brains of infected mice and to identify the key molecules and cells involved in development of ECM.