Blood-cerebrospinal fluid barrier: another site disrupted during experimental cerebral malaria caused by Plasmodium berghei ANKA
Blood-cerebrospinal fluid barrier: another site disrupted during experimental cerebral malaria caused by Plasmodium berghei ANKA
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DOI：
10.1016/j.ijpara.2020.07.007
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发表时间：
2020-12-01
影响因子：
4
通讯作者：
Imai, Takashi
中科院分区：
文献类型：
--
作者：
Ha Ngo-Thanh;Sasaki, Tsutomu;Imai, Takashi
脑型疟疾是疟疾最严重的病理之一;它引起神经认知后遗症，死亡率高。虽然脑型疟疾的发病因素很多，但其发病机制仍不完全清楚。大多数关于脑型疟疾的研究都集中在血脑屏障上，尽管血-脑脊液屏障的重要性，它保护大脑免受外周炎症的影响。因此，血-脑脊液屏障在脑型疟疾中的病理作用目前尚不清楚。为了检查脑型疟疾和无此病理的疟疾（非脑型疟疾）中血-脑脊液屏障的状态，我们开发了一种新方法，用于评估小鼠脑型疟疾期间血-脑脊液屏障的透化，使用Evans蓝染料和软件辅助图像分析。以伯氏疟原虫ANKA株感染的C57 BL/6 J（B6）小鼠为实验性脑型疟疾模型，以伯氏疟原虫NK 65株或约氏疟原虫感染的B6小鼠为非脑型疟疾模型，发现实验性脑型疟疾时血-脑脊液屏障通透性增加，而非脑型疟疾时血-脑脊液屏障通透性不增加。我们在脑型疟疾小鼠中观察到脑室出血和脉络丛中的疟原虫色素样结构，脉络丛是血液-脑脊液屏障的关键组成部分。总之，这一证据表明，血-脑脊液屏障在实验性脑型疟疾中被破坏，而在非脑型疟疾中保持完整。我们还发现伯氏疟原虫ANKA寄生虫和CD 8（+）T细胞参与了实验性脑型疟疾的血-脑脊液屏障破坏。了解脑型疟疾的潜在机制可能有助于制定有效的策略来预防和管理人类脑型疟疾。(C)2020年澳大利亚寄生虫学会。由爱思唯尔有限公司出版。保留所有权利。
Cerebral malaria is one of the most severe pathologies of malaria; it induces neuro-cognitive sequelae and has a high mortality rate. Although many factors involved in the development of cerebral malaria have been discovered, its pathogenic mechanisms are still not completely understood. Most studies on cerebral malaria have focused on the blood-brain barrier, despite the importance of the blood-cerebrospinal fluid barrier, which protects the brain from peripheral inflammation. Consequently, the pathological role of the blood-cerebrospinal fluid barrier in cerebral malaria is currently unknown. To examine the status of the blood-cerebrospinal fluid barrier in cerebral malaria and malaria without this pathology (non-cerebral malaria), we developed a new method for evaluating the permeabilization of the blood-cerebrospinal fluid barrier during cerebral malaria in mice, using Evans blue dye and a software-assisted image analysis. Using C57BL/6J (B6) mice infected with Plasmodium berghei ANKA strain as an experimental cerebral malaria model and B6 mice infected with P. berghei NK65 strain or Plasmodium yoelii as non-cerebral malaria models, we revealed that the permeability of the blood-cerebrospinal fluid barrier increased during experimental cerebral malaria but not during non-cerebral malaria. We observed haemorrhaging in the cerebral ventricles and hemozoin-like structures in the choroid plexus, which is a key component of the blood-cerebrospinal fluid barrier, in cerebral malaria mice. Taken together, this evidence indicates that the blood-cerebrospinal fluid barrier is disrupted in experimental cerebral malaria, whereas it remains intact in non-cerebral malaria. We also found that P. berghei ANKA parasites and CD8(+) T cells are involved in the blood-cerebrospinal fluid barrier disruption in experimental cerebral malaria. An understanding of the mechanisms underlying cerebral malaria might help in the development of effective strategies to prevent and manage cerebral malaria in humans. (C) 2020 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.