Sepsis-induced changes in behavioral stereotypy in rats; involvement of tumor necrosis factor-alpha, oxidative stress, and dopamine turnover

Sepsis-induced changes in behavioral stereotypy in rats; involvement of tumor necrosis factor-alpha, oxidative stress, and dopamine turnover
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DOI:
10.1016/j.jss.2013.08.001
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发表时间:
2014-01-01
影响因子:
2.2
通讯作者:
Taskiran, Dilek
Taskiran, Dilek
中科院分区:
医学3区
文献类型:
--
作者:
Erbas, Oytun;Taskiran, Dilek

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背景:脓毒症相关性脑病(SAE)是一种弥漫性或多灶性脑功能障碍,通常在严重脓毒症早期发生。SAE的完整病理生理机制尚不清楚,但已有多种机制被提出,包括内毒素、炎症介质、氨基酸和神经递质的改变、细胞凋亡、氧化应激和血脑屏障功能障碍。本研究旨在探讨手术诱导脓毒症大鼠行为刻板印象与血浆肿瘤坏死因子-α(TNF-α)、丙二醛(脂质过氧化标志物)和脑高香草酸含量(多巴胺代谢标志物)的关系。材料和方法:成年雄性SD大鼠22只。采用盲肠结扎穿刺法复制脓毒症模型。结果:脓毒症组大鼠刻板行为评分明显高于假手术组(P=0.008)。此外,脓毒症大鼠血浆肿瘤坏死因子-α(P=0.002)、丙二醛(P=0.002)和脑高香草酸(P=0.004)水平显著高于假手术组大鼠。结论:在一个实验性脓毒症模型中,这些结果证实了炎症反应、氧化应激和刻板行为之间的关联。需要更全面的实验和临床研究来阐明SAE的具体机制。(C)2014 Elsevier Inc.保留所有权利。
Background: Sepsis-associated encephalopathy (SAE) is defined as a diffuse or multifocal cerebral dysfunction that generally occurs early during severe sepsis. The complete pathophysiology of SAE is unknown, but several mechanisms including endotoxins, inflammatory mediators, the alteration of amino acids and of neurotransmitters, apoptosis, oxidative stress, and blood-brain barrier dysfunction have been suggested. The aim of the present study was to explore the relationship between behavioral stereotypy and plasma levels of tumor necrosis factor-alpha (TNF-alpha) and malondialdehyde (a marker of lipid peroxidation), and brain homovanillic acid content (a marker of dopamine turnover) in a surgically induced sepsis model in rats.Materials and methods: Twenty-two adult male Sprague Dawley rats were included in the study. The cecal ligation and puncture procedure was performed to induce sepsis model. Apomorphine-induced stereotypy test was achieved 24 h after cecal ligation and puncture surgery and then, blood and brain samples were collected for biochemical measurements.Results: Significantly higher stereotypy score was found in sepsis group than in the sham group (P = 0.008). Furthermore, septic rats revealed significantly higher plasma TNF-alpha (P = 0.002) and malondialdehyde levels (P = 0.002), and brain homovanillic acid (P = 0.004) compared with sham rats. There was a significant and positive correlation between the behavioral and biochemical parameters.Conclusions: Taken together, these results demonstrate the association between inflammatory response, oxidative stress, and stereotypic behavior in an experimental sepsis model. More comprehensive experimental and clinical studies are required to clarify the specific mechanisms underlying SAE. (C) 2014 Elsevier Inc. All rights reserved.