Sepsis-induced morbidity in mice: effects on body temperature, body weight, cage activity, social behavior and cytokines in brain.
Sepsis-induced morbidity in mice: effects on body temperature, body weight, cage activity, social behavior and cytokines in brain.
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DOI：
10.1016/j.psyneuen.2012.10.010
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发表时间：
2013-07
影响因子：
3.7
通讯作者：
Opp, Mark R.
中科院分区：
文献类型：
--
作者：
Granger, Jill I.;Ratti, Pietro-Luca;Datta, Subhash C.;Raymond, Richard M.;Opp, Mark R.
感染会对心理健康产生负面影响，疾病期间的嗜睡、不适和认知缺陷就证明了这一点。中枢神经系统过程的这些变化统称为疾病行为，已在动物模型中显示主要由大脑中细胞因子的作用介导。迄今为止，大多数疾病行为研究都使用推注细菌脂多糖 (LPS) 或选择性施用促炎细胞因子白介素-1β (IL-1β) 或 IL-6 作为免疫攻击。这些模型虽然可用于确定导致生理和行为急剧变化的机制，但并不能充分代表复制病原体的真正感染对中枢神经系统（CNS）过程的更复杂影响。在本研究中，我们使用盲肠结扎穿刺（CLP）模型来量化脓毒症引起的小鼠生理和行为多个方面的变化。我们确定了败血症对小鼠笼内活动、体温、食物和水消耗以及体重的影响。由于细胞因子是免疫挑战期间行为和温度调节变化的关键介质，因此我们还量化了脓毒症发作急性期脓毒症引起的脑细胞因子 mRNA 和蛋白质的变化。我们现在报道，存活小鼠的笼子活动和温度调节在脓毒症诱导后长达 23 天内发生改变。脓毒症期间食物和水的消耗暂时减少，体重减轻。此外，脓毒症会在 24-48 小时内减少社交互动。最后，脓毒症发作期间（脓毒症诱导后 6-72 小时）下丘脑、海马和脑干中 IL-1β、IL-6 和肿瘤坏死因子-α (TNFα) 的 mRNA 和蛋白质上调。总的来说，这些数据表明，脓毒症不仅会急剧改变大脑的生理、行为和细胞因子谱，而且存活动物的某些大脑功能会长期受损。
Infection negatively impacts mental health, as evidenced by the lethargy, malaise, and cognitive deficits experienced during illness. These changes in central nervous system processes, collectively termed sickness behavior, have been shown in animal models to be mediated primarily by the actions of cytokines in brain. Most studies of sickness behavior to date have used bolus injection of bacterial lipopolysaccharide (LPS) or selective administration of the proinflammatory cytokines interleukin-1β (IL-1β) or IL-6 as the immune challenge. Such models, although useful for determining mechanisms responsible for acute changes in physiology and behavior, do not adequately represent the more complex effects on central nervous system (CNS) processes of a true infection with replicating pathogens. In the present study, we used the cecal ligation and puncture (CLP) model to quantify sepsis-induced alterations in several facets of physiology and behavior of mice. We determined the impact of sepsis on cage activity, body temperature, food and water consumption and body weights of mice. Because cytokines are critical mediators of changes in behavior and temperature regulation during immune challenge, we also quantified sepsis-induced alterations in cytokine mRNA and protein in brain during the acute period of sepsis onset. We now report that cage activity and temperature regulation in mice that survive are altered for up to 23 days after sepsis induction. Food and water consumption are transiently reduced, and body weight is lost during sepsis. Furthermore, sepsis decreases social interactions for 24 – 48 hours. Finally, mRNA and protein for IL-1β, IL-6, and tumor necrosis factor-α (TNFα) are upregulated in the hypothalamus, hippocampus, and brain stem during sepsis onset, from 6–72 hour post sepsis induction. Collectively, these data indicate that sepsis not only acutely alters physiology, behavior and cytokine profiles in brain, but that some brain functions are impaired for long periods in animals that survive.
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影响因子：
3.1
作者：
Ebong, SJ;Call, DR;Remick, DG
通讯作者：
Remick, DG
DOI：
10.1164/ajrccm.163.2.9912128
发表时间：
2001-02-01
影响因子：
24.7
作者：
Freedman, NS;Gazendam, J;Schwab, RJ
通讯作者：
Schwab, RJ
影响因子：
15.1
作者：
Chen, Jing;Buchanan, Jessica B.;Johnson, Rodney W.
通讯作者：
Johnson, Rodney W.
影响因子：
3.7
作者：
BLUTHE, RM;PAWLOWSKI, M;DANTZER, R
通讯作者：
DANTZER, R
影响因子：
2.9
作者：
Harden, Lois M.;du Plessis, Irne;Laburn, Helen P.
通讯作者：
Laburn, Helen P.