Cerebral Malaria (CM) is associated with the complex neurological syndrome, whose pathology is mediated by severe inflammatory processes following infection with Plasmodium falciparum. Coenzyme-Q₁₀ (Co-Q₁₀) is a potent anti-inflammatory, anti-oxidant, and anti-apoptotic agent with numerous clinical applications. The aim of this study was to elucidate the role of oral administration of Co-Q₁₀ on the initiation or regulation of inflammatory immune response during experimental cerebral malaria (ECM). For this purpose, the pre-clinical effect of Co-Q₁₀ was evaluated in C57BL/6 J mice infected with Plasmodium berghei ANKA (PbA). Treatment with Co-Q₁₀ resulted in the reduction of infiltrating parasite load, greatly improved the survival rate of PbA-infected mice that occurred independent of parasitaemia and prevented PbA-induced disruption of the blood-brain barrier (BBB) integrity. Exposure to Co-Q₁₀ resulted in the reduction of infiltration of effector CD8 + T cells in the brain and secretion of cytolytic Granzyme B molecules. Notably, Co-Q₁₀-treated mice had reduced levels of CD8 +T cell chemokines CXCR3, CCR2, and CCR5 in the brain following PbA-infection. Brain tissue analysis showed a reduction in the levels of inflammatory mediators TNF- α, CCL3, and RANTES in Co-Q₁₀ administered mice. In addition, Co-Q₁₀ modulated the differentiation and maturation of both splenic and brain dendritic cells and cross-presentation (CD8α+DCs) during ECM. Remarkably, Co-Q₁₀ was very effective in decreasing levels of CD86, MHC-II, and CD40 in macrophages associated with ECM pathology. Exposure to Co-Q₁₀ resulted in increased expression levels of Arginase-1 and Ym1/chitinase 3–like 3, which is linked to ECM protection. Furthermore, Co-Q₁₀ supplementation prevented PbA-induced depletion of Arginase and CD206 mannose receptor levels. Co-Q₁₀ abrogated PbA-driven elevation in pro-inflammatory cytokines IL-1β, IL-18, and IL-6 levels. In conclusion, the oral supplementation with Co-Q₁₀ decelerates the occurrence of ECM by preventing lethal inflammatory immune responses and dampening genes associated with inflammation and immune-pathology during ECM, and offers an inimitable opening for developing an anti-inflammatory agent against cerebral malaria.

脑型疟疾（CM）与复杂的神经系统综合征相关，其病理学是由恶性疟原虫感染后的严重炎症过程介导的。辅酶-Q ₁₀ (Co-Q ₁₀ ) 是一种有效的抗炎、抗氧化和抗凋亡剂，具有广泛的临床应用。本研究的目的是阐明口服 Co-Q ₁₀对实验性脑型疟疾 (ECM) 期间炎症免疫反应的启动或调节的作用。为此，在感染伯氏疟原虫ANKA (PbA)的 C57BL/6 J 小鼠中评估了Co-Q _{10的临床前效果。Co-Q 10}治疗可减少浸润寄生虫负荷，大大提高 PbA 感染小鼠的存活率（与寄生虫血症无关），并防止 PbA 诱导的血脑屏障 (BBB) 完整性破坏。暴露于 Co-Q _10会导致大脑中效应 CD8 + T 细胞的浸润减少以及溶细胞颗粒酶 B 分子的分泌减少。值得注意的是，Co-Q _{10治疗的小鼠}在 PbA 感染后大脑中CD8 + T 细胞趋化因子CXCR3、 CCR2和 CCR5的水平降低。脑组织分析显示，给予 Co-Q ₁₀的小鼠炎症介质 TNF-α、CCL3 和RANTES水平降低。此外，Co-Q ₁₀调节脾和脑树突状细胞的分化和成熟以及 ECM 期间的交叉呈递 (CD8α+DC)。值得注意的是，Co-Q ₁₀在降低与 ECM 病理相关的巨噬细胞中 CD86、MHC-II 和 CD40 水平方面非常有效。暴露于 Co-Q ₁₀会导致 Arginase-1 和 Ym1/几丁质酶 3-like 3 的表达水平增加，这与 ECM 保护有关。此外，补充 Co-Q ₁₀可以防止 PbA 诱导的精氨酸酶和 CD206 甘露糖受体水平的消耗。Co-Q ₁₀消除了 PbA 驱动的促炎细胞因子 IL-1β、IL-18 和 IL-6 水平的升高。总之，口服补充 Co-Q ₁₀可通过预防致死性炎症免疫反应并抑制 ECM 期间与炎症和免疫病理学相关的基因来减缓 ECM 的发生，并为开发针对脑型疟疾的抗炎剂提供了独特的机会。