A Cecal Slurry Mouse Model of Sepsis Leads to Acute Consumption of Vitamin C in the Brain
A Cecal Slurry Mouse Model of Sepsis Leads to Acute Consumption of Vitamin C in the Brain
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DOI：
10.3390/nu12040911
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发表时间：
2020-04-01
期刊：
影响因子：
5.9
通讯作者：
Harrison, Fiona E.
中科院分区：
文献类型：
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作者：
Consoli, David C.;Jesse, Jordan J.;Harrison, Fiona E.
维生素C（抗坏血酸盐，ASC）是体内重要的抗氧化剂，在大脑中发挥特定作用。尽管最近对维生素C治疗重症监护医学感兴趣，但对急性炎症和败血症等危重疾病期间的维生素C调节知之甚少。使用小鼠盲肠浆液（CS）脓毒症模型，我们确定了初始治疗后大脑中的ASC和炎症变化。在CS处理后4和24小时，脑中的ASC水平急剧下降约10%。变化伴随着高达50%的肝脏ASC水平的稳健增加，表明CS处理后4小时开始合成上调并持续长达7天。CS治疗后4 h，皮质中几种关键细胞因子白细胞介素6（IL-6）、白细胞介素1 β（IL-1 β）、肿瘤坏死因子α（TNF α）和趋化因子（C-X-C基序）配体1（CXCL 1，KC/Gro）也显著升高，尽管这些水平在48 h时恢复正常。这些数据强烈表明，ASC储备在整个疾病和脓毒症恢复过程中受到直接挑战。考虑到这种反应的时间尺度，皮质ASC的减少可能是由超急性神经炎症过程驱动的。然而，未来的研究需要证实这种关系，并研究这种缺陷如何影响神经炎症。
Vitamin C (ascorbate, ASC) is a critical antioxidant in the body with specific roles in the brain. Despite a recent interest in vitamin C therapies for critical care medicine, little is known about vitamin C regulation during acute inflammation and critical illnesses such as sepsis. Using a cecal slurry (CS) model of sepsis in mice, we determined ASC and inflammatory changes in the brain following the initial treatment. ASC levels in the brain were acutely decreased by approximately 10% at 4 and 24 h post CS treatment. Changes were accompanied by a robust increase in liver ASC levels of up to 50%, indicating upregulation of synthesis beginning at 4 h and persisting up to 7 days post CS treatment. Several key cytokines interleukin 6 (IL-6), interleukin 1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), and chemokine (C-X-C motif) ligand 1 (CXCL1, KC/Gro) were also significantly elevated in the cortex at 4 h post CS treatment, although these levels returned to normal by 48 h. These data strongly suggest that ASC reserves are directly challenged throughout illness and recovery from sepsis. Given the timescale of this response, decreases in cortical ASC are likely driven by hyper-acute neuroinflammatory processes. However, future studies are required to confirm this relationship and to investigate how this deficiency may subsequently impact neuroinflammation.