Lima Maiara N, Freitas Rodrigo J R X, Passos Beatriz A B R, Darze Ana Maria G, Castro-Faria-Neto Hugo C, Maron-Gutierrez Tatiana
Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Fiocruz, Rio de Janeiro, Brazil.
National Institute of Science and Technology on Neuroimmunomodulation, Rio de Janeiro, Brazil.
Neuroimmunomodulation. 2021;28(3):108-117. doi: 10.1159/000515557. Epub 2021 May 5.
Malaria is caused by Plasmodium infection and remains a serious public health problem worldwide, despite control efforts. Malaria can progress to severe forms, affecting multiple organs, including the brain causing cerebral malaria (CM). CM is the most severe neurological complication of malaria, and cognitive and behavior deficits are commonly reported in surviving patients. The number of deaths from malaria has been reducing in recent years, and as a consequence, neurological sequelae have been more evident. Neurological damage in malaria might be related to the neuroinflammation, characterized by glia cell activation, neuronal apoptosis and changes in the blood-brain barrier (BBB) integrity. The neurovascular unit (NVU) is responsible for maintaining the homeostasis of the BBB. Endothelial and pericytes cells in the cerebral microvasculature and neural cells, as astrocytes, neurons, and microglia, compose the NVU. The NVU can be disturbed by parasite metabolic products, such as heme and hemozoin, or cytokines that can promote activation of endothelial and glial cells and lead to increased BBB permeability and subsequently neurodegeneration. In this review, we will approach the main changes that happen in the cells of the NVU due to neuroinflammation caused by malaria infection, and elucidate how the systemic pathophysiology is involved in the onset and progression of CM.
疟疾由疟原虫感染引起，尽管采取了防控措施，但仍是全球严重的公共卫生问题。疟疾可发展为严重形式，影响包括大脑在内的多个器官，导致脑型疟疾（CM）。CM是疟疾最严重的神经并发症，存活患者中普遍存在认知和行为缺陷。近年来，疟疾死亡人数一直在减少，因此，神经后遗症愈发明显。疟疾中的神经损伤可能与神经炎症有关，其特征为胶质细胞活化、神经元凋亡以及血脑屏障（BBB）完整性改变。神经血管单元（NVU）负责维持BBB的稳态。脑微血管中的内皮细胞、周细胞以及神经细胞，如星形胶质细胞、神经元和小胶质细胞，共同构成NVU。NVU可能会受到寄生虫代谢产物（如血红素和疟色素）或细胞因子的干扰，这些物质可促进内皮细胞和胶质细胞的活化，导致BBB通透性增加，进而引发神经退行性变。在本综述中，我们将探讨由于疟疾感染引起的神经炎症，NVU细胞中发生的主要变化，并阐明全身病理生理学如何参与CM的发生和发展。
