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首页> 外文期刊>BMC Neuroscience >TNF-α antagonist attenuates systemic lipopolysaccharide-induced brain white matter injury in neonatal rats
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TNF-α antagonist attenuates systemic lipopolysaccharide-induced brain white matter injury in neonatal rats

机译：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

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Systemic 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. We 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. It 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.
机译：全身炎症是早产儿神经发育受损的重要危险因素。早髓鞘少突胶质细胞是早产儿白质的主要组成部分，易受氧化应激和兴奋毒性应激的影响。肿瘤坏死因子-α（TNF-α）在全身性炎症和局部炎症中起重要作用，导致前髓鞘少突胶质细胞凋亡和脑组织白质损伤（WMI）。进行这项研究以调查依那西普（TNF-α拮抗剂）是否能减弱未成熟大脑中全身性脂多糖（LPS）诱导的WMI。我们发现腹膜内给予LPS会引起脑组织的全身性和局部性炎症。随后的依那西普治疗显着减轻了LPS诱导的脑组织以及全身循环中的炎症。腹膜内脂多糖也可引起扣带小胶质细胞增生和星形胶质细胞增多，依那西普治疗可减少脂多糖引起的胶质细胞增生和星形胶质细胞增多。另外，观察到系统性LPS诱导的少突胶质细胞前体细胞的凋亡，这通过依那西普处理而减少。用LPS给药时，依那西普在脑脊液中的浓度高于用媒介物给药时。依那西普似乎通过减轻全身和局部炎症减轻了新生鼠脑中的WMI。这项研究提供的临床前数据表明，依那西普介导的炎症调节是减少早产儿败血症或坏死性小肠结肠炎引起的WMI的一种有前途的方法。

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