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手术创伤严重程度而非麻醉时间长短导致小鼠术后认知功能障碍。

Surgery Trauma Severity but not Anesthesia Length Contributes to Postoperative Cognitive Dysfunction in Mice.

机构信息

Department of Anesthesiology, University of Virginia, Charlottesville, VA, USA.

Department of Anesthesiology, Fujian Medical University Union Hospital, Fuzhou, China.

出版信息

J Alzheimers Dis. 2021;80(1):245-257. doi: 10.3233/JAD-201232.

DOI:10.3233/JAD-201232
PMID:33523008
Abstract

BACKGROUND

Perioperative, modifiable factors contributing to perioperative neurocognitive disorders (PND) have not been clearly defined.

OBJECTIVE

To determine the contribution of anesthesia lengths and the degrees of surgical trauma to PND and neuroinflammation, a critical process for PND.

METHODS

Three-month-old C57BL/6J mice were subjected to 2 h or 6 h isoflurane anesthesia plus a 5 min or 15 min left common carotid artery exposure (surgery) in a factorial design (two factors: anesthesia with two levels and surgery with three levels). Their learning and memory were tested by Barnes maze and novel object recognition paradigms. Blood, spleen, and hippocampus were harvested for measuring interleukin (IL)-6 and IL-1β. Eighteen-month-old C57BL/6J mice (old mice) were subjected to 6 h isoflurane anesthesia or 2 h isoflurane anesthesia plus 15 min surgery and then had learning and memory tested.

RESULTS

Three-month-old mice with 15 min surgery (long surgery) under 2 h or 6 h anesthesia performed poorly in the learning and memory tests compared with controls. Anesthesia alone or anesthesia plus 5 min surgery did not affect mouse performance in these tests. Similarly, only mice with long surgery but not mice with other experimental conditions had increased IL-6 and IL-1β in the blood, spleen, and hippocampus and decreased spleen weights. Splenocytes were found in the hippocampus after surgery. Similarly, old mice with long surgery but not the mice with isoflurane anesthesia alone had poor performance in the Barnes maze and novel object recognition tests.

CONCLUSION

Surgical trauma, but not anesthesia, contributes to the development of PND and neuroinflammation. Splenocytes may modulate these processes.

摘要

背景

围手术期可改变的因素导致围手术期神经认知障碍(PND)尚未明确界定。

目的

确定麻醉时间和手术创伤程度对 PND 和神经炎症的影响,神经炎症是 PND 的关键过程。

方法

采用两因素析因设计,将 3 个月大的 C57BL/6J 小鼠暴露于 2 小时或 6 小时异氟烷麻醉加 5 分钟或 15 分钟左颈总动脉(手术),检测其学习和记忆能力(巴恩斯迷宫和新物体识别范式)。采血、脾脏和海马组织,检测白细胞介素(IL)-6 和 IL-1β。18 个月大的 C57BL/6J 小鼠(老年小鼠)接受 6 小时异氟烷麻醉或 2 小时异氟烷麻醉加 15 分钟手术,然后进行学习和记忆测试。

结果

3 个月大的小鼠,在 2 小时或 6 小时麻醉下接受 15 分钟手术(长手术),在学习和记忆测试中的表现明显差于对照组。单独麻醉或麻醉加 5 分钟手术不影响这些测试中小鼠的表现。同样,只有长手术的小鼠而不是其他实验条件的小鼠,血液、脾脏和海马组织中的 IL-6 和 IL-1β 增加,脾脏重量减轻。手术后发现海马中有脾细胞。同样,只有长手术的老年小鼠而不是单独接受异氟烷麻醉的小鼠,在巴恩斯迷宫和新物体识别测试中表现不佳。

结论

手术创伤而不是麻醉会导致 PND 和神经炎症的发生。脾细胞可能调节这些过程。

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