BackgroundSystemic inflammation is an important risk factor for neurodevelopmental impairments in preterm infants. Premyelinating oligodendrocytes are main building blocks of white matter in preterm infants and vulnerable to oxidative stress and excitotoxic stress. Tumour necrosis factor-α (TNF-α) plays important roles in systemic inflammation and local inflammation leading to apoptosis of premyelinating oligodendrocytes and white matter injury (WMI) in brain tissue. This study was conducted to investigate whether etanercept, a TNF-α antagonist, could attenuate systemic lipopolysaccharide (LPS)-induced WMI in the immature brain.ResultsWe found that intraperitoneal LPS administration caused systemic and local inflammation in brain tissue. Subsequent etanercept treatment significantly attenuated LPS-induced inflammation in brain tissue as well as in systemic circulation. Intraperitoneal LPS also induced microgliosis and astrocytosis in the cingulum and etanercept treatment reduced LPS-induced microgliosis and astrocytosis. Additionally, systemic LPS-induced apoptosis of oligodendrocyte precursor cells was observed, which was lessened by etanercept treatment. The concentration of etanercept in the CSF was higher when it was administrated with LPS than when administrated with a vehicle.ConclusionsIt appears that etanercept reduce WMI in the neonatal rat brain via attenuation of systemic and local inflammation. This study provides preclinical data suggesting etanercept-mediated modulation of inflammation as a promising approach to reduce WMI caused by sepsis or necrotizing enterocolitis in preterm infants.

中文翻译：

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TNF-α拮抗剂减轻新生大鼠全身性脂多糖诱导的脑白质损伤

背景全身炎症是早产儿神经发育障碍的重要危险因素。髓鞘形成前少突胶质细胞是早产儿白质的主要组成部分，容易受到氧化应激和兴奋性毒性应激的影响。肿瘤坏死因子-α (TNF-α) 在全身炎症和局部炎症中发挥重要作用，导致前髓鞘少突胶质细胞凋亡和脑组织白质损伤 (WMI)。本研究旨在研究依那西普（一种 TNF-α 拮抗剂）是否可以减轻未成熟大脑中全身性脂多糖 (LPS) 诱导的 WMI。结果我们发现腹腔内 LPS 给药会引起脑组织的全身性和局部炎症。随后的依那西普治疗显着减轻了 LPS 诱导的脑组织和体循环炎症。腹腔内 LPS 还诱导扣带中的小胶质细胞增生和星形细胞增多症，依那西普治疗减少了 LPS 诱导的小胶质细胞增生和星形细胞增多症。此外，还观察到全身性 LPS 诱导少突胶质细胞前体细胞凋亡，依那西普治疗可减轻这种凋亡。与 LPS 一起给药时，CSF 中的依那西普浓度高于与载体一起给药时。结论 依那西普似乎通过减轻全身和局部炎症来降低新生大鼠脑中的 WMI。