Anesthesia/surgery leads to blood-brain barrier disruption via the transcellular and paracellular pathways, and postoperative delirium-like behavior: A comparative study in mice of different ages

IF 4.6 2区医学 Q1 NEUROSCIENCES

Experimental Neurology Pub Date : 2024-11-05 DOI:10.1016/j.expneurol.2024.115044

Xudong Hu , Lixia Liu , Xin Da , Sihui Zhu , Jiawei Wang , Menglei Shan , Yinuo Liu , Ziqing He , Guanghong Xu

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引用次数: 0

Abstract

Aims

Postoperative delirium (POD) is a common complication of anesthesia and surgery, with a higher incidence in elderly patients. Disruption of the blood-brain barrier (BBB) is considered one of the key mechanisms underlying POD. Therefore, the present study aimed to investigate the effects of different BBB permeability alteration pathways on POD in mice of various ages.

Methods

C57BL/6 J mice aged 4 and 16 months underwent exploratory laparotomy under sevoflurane anesthesia. Behavioral tests were conducted 24 h prior to surgery, as well as 6, 9, and 24 h postoperatively. Frontal cortex tissue was collected to detect the levels of BBB-related proteins and mRNA.

Results

At 6 and 9 h after anesthesia/surgery, 4-month-old mice showed poorer performance on behavioral tests than their untreated counterparts. However, 16-month-old mice exhibited worse behavioral test results at 6, 9, and 24 h after surgery. Anesthesia/surgery 6 h postoperatively increased the expression of vesicle-associated proteins, and BBB leakage in 4-month-old mice. In 16-month-old mice, anesthesia/surgery altered the expression of tight junction proteins, vesicle-associated proteins, and BBB leakage at 6 and 24 h postoperatively.

Conclusion

Overall, our results suggest that anesthesia/surgery leads to age-dependent cognitive decline, and is associated with differences in the BBB injury pathways among mice of different ages. The transcellular pathway (transcytosis), compared to the paracellular pathway (tight junction), is more vulnerable to damage following anesthesia/surgery. This study provides new evidence for the improvement of POD through protection of the BBB.

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麻醉/手术会通过跨细胞和旁细胞途径导致血脑屏障破坏，并导致术后类似谵妄的行为：不同年龄小鼠的比较研究。

目的：术后谵妄（POD）是麻醉和手术的常见并发症，老年患者的发病率更高。血脑屏障（BBB）的破坏被认为是导致 POD 的关键机制之一。因此，本研究旨在探讨不同BBB通透性改变途径对不同年龄小鼠POD的影响：方法：年龄分别为 4 个月和 16 个月的 C57BL/6 J 小鼠在七氟醚麻醉下接受探查性开腹手术。在手术前 24 小时以及术后 6、9 和 24 小时进行行为测试。采集额叶皮层组织检测BBB相关蛋白和mRNA的水平：麻醉/手术后 6 和 9 小时，4 个月大的小鼠在行为测试中的表现比未接受治疗的小鼠差。然而，16 个月大的小鼠在术后 6、9 和 24 小时的行为测试结果更差。术后 6 小时的麻醉/手术增加了囊泡相关蛋白的表达，并增加了 4 个月大小鼠的 BBB 渗漏。在 16 个月大的小鼠中，麻醉/手术改变了紧密连接蛋白、囊泡相关蛋白以及术后 6 小时和 24 小时 BBB 渗漏的表达：总之，我们的研究结果表明，麻醉/手术导致认知能力下降与年龄有关，并与不同年龄小鼠的 BBB 损伤途径差异有关。与细胞旁通路（紧密连接）相比，跨细胞通路（转胞作用）在麻醉/手术后更容易受到损伤。这项研究为通过保护 BBB 改善 POD 提供了新的证据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Experimental Neurology 医学-神经科学

CiteScore

10.10

自引率

3.80%

发文量

258

审稿时长

42 days

期刊介绍： Experimental Neurology, a Journal of Neuroscience Research, publishes original research in neuroscience with a particular emphasis on novel findings in neural development, regeneration, plasticity and transplantation. The journal has focused on research concerning basic mechanisms underlying neurological disorders.