Brooks Hannah M, Hawkes Michael T
Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
Curr Clin Pharmacol. 2017;12(2):62-72. doi: 10.2174/1574884712666170704144042.
Cerebral malaria (CM) is a severe complication of infection which may result in death or developmental disability. The pathologic processes leading to CM are not fully elucidated; however, widely accepted mechanisms include parasite sequestration, release of infected red blood cell contents, activation of endothelial cells, increased inflammatory responses, and ultimately dysfunction of the neurovascular unit (NVU). The endothelium plays a central role in these processes as the site of parasitized erythrocyte sequestration and as the regulator of fluid extravasation into the central nervous system. Modulating endothelial barrier function at the NVU may provide new therapeutic approaches to improve outcomes in CM.
Here we provide a narrative review of the literature of peer-reviewed research relating to adjunctive therapies for CM. We discuss regulatory pathways of the NVU, with a focus on the potential for pharmacologic modulation of the NVU to improve CM outcomes.
Recently licensed pharmaceuticals, developed as therapies for cancer or neurologic disease, could be re-purposed for use as host-directed therapies in CM to target pathways involved in endothelial stability and activation.
The findings of this review highlight recently licensed pharmaceuticals that may be developed as future adjunctive therapies for CM.
脑型疟疾（CM）是感染的一种严重并发症，可能导致死亡或发育残疾。导致脑型疟疾的病理过程尚未完全阐明；然而，广泛接受的机制包括寄生虫滞留、受感染红细胞内容物的释放、内皮细胞的激活、炎症反应增加以及最终神经血管单元（NVU）功能障碍。内皮细胞在这些过程中起着核心作用，既是被寄生红细胞滞留的部位，也是液体渗入中枢神经系统的调节者。调节神经血管单元处的内皮屏障功能可能为改善脑型疟疾的预后提供新的治疗方法。
在此，我们对有关脑型疟疾辅助治疗的同行评审研究文献进行叙述性综述。我们讨论神经血管单元的调节途径，重点关注对神经血管单元进行药理学调节以改善脑型疟疾预后的可能性。
最近获批用于治疗癌症或神经系统疾病的药物可重新用于作为脑型疟疾的宿主导向疗法，以靶向参与内皮稳定性和激活的途径。
本综述的结果突出了可能被开发为未来脑型疟疾辅助治疗药物的近期获批药物。
