Systemic inflammation enhances surgery-induced cognitive dysfunction in mice

Systemic inflammation enhances surgery-induced cognitive dysfunction in mice
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DOI:
10.1016/j.neulet.2011.04.063
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发表时间:
2011-07-01
影响因子:
2.5
通讯作者:
Ma, Daqing
Ma, Daqing
中科院分区:
医学4区
文献类型:
--
作者:
Fidalgo, Antonio Rei;Cibelli, Mario;Ma, Daqing

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通过脂多糖 (LPS) 给药或手术创伤激活免疫系统已被证明能够影响海马功能,导致记忆障碍。在这里,我们研究了 LPS 诱导的感染可能在多大程度上加重骨科手术后记忆功能的损害。使用恐惧调节任务评估海马记忆功能损伤,同时使用 ELISA 测量血浆和海马中的 IL-1 β 水平。 LPS 诱导的炎症破坏了海马记忆巩固,感染小鼠表现出的情境冻结时间减少就证明了这一点。同样,手术会导致海马依赖性记忆损伤,这与血浆和海马中 IL-1 β 水平升高有关。然而,单独使用亚热原剂量的 LPS 并不能损害记忆功能。当在手术前施用该剂量的 LPS 时,会加剧手术引起的认知功能障碍,如上下文冻结时间的进一步减少所证明的那样。此外,它还导致这些动物的血浆和海马中 IL-1β 水平随之额外增加。我们的数据表明,亚临床感染可能会使免疫系统变得敏感,从而加剧术后认知功能障碍的严重程度。 (C) 2011 Elsevier Ireland Ltd. 保留所有权利。
The activation of the immune system, by either lipopolysaccharide (LPS) administration or surgical trauma, has been shown to be capable of affecting hippocampal function, causing memory impairment. Here, we examined the extent to which LPS-induced infection may aggravate impairment of memory function following orthopaedic surgery. Hippocampal memory function impairment was assessed using fear-conditioning tasks, while IL-1 beta levels in plasma and hippocampus were measured using ELISA. LPS-induced inflammation disrupted hippocampal memory consolidation as evidenced by reduced contextual freezing time exhibited by infected mice. Likewise, surgery caused hippocampal-dependent memory impairment, which was associated with increased levels of IL-1 beta both in plasma and hippocampus. However, a sub-pyrogenic dose of LPS alone failed to impair memory function. This dose of LPS, when administered prior to surgery, exacerbated surgery-induced cognitive dysfunction as evidenced by further reduction of contextual freezing time. Also, it caused a concomitant additional increase in the levels of IL-1 beta in both plasma and hippocampus of those animals. Our data suggest that sub-clinical infection may sensitise the immune system augmenting the severity of post-operative cognitive dysfunction. (C) 2011 Elsevier Ireland Ltd. All rights reserved.