结肠VIP过表达可改善七氟醚麻醉和手术对脑功能脆弱的老年大鼠认知功能和屏障系统的损害。

IF 4.6 2区医学 Q1 NEUROSCIENCES

Experimental Neurology Pub Date : 2025-05-31 DOI:10.1016/j.expneurol.2025.115328

Huihui Liao , Xinyi Wang , Chenyi Yang , Zixuan Wang , Xing Liu , Huan Liu , Jingwei Zhang , Huai Shen , Haiyun Wang

{"title":"结肠VIP过表达可改善七氟醚麻醉和手术对脑功能脆弱的老年大鼠认知功能和屏障系统的损害。","authors":"Huihui Liao , Xinyi Wang , Chenyi Yang , Zixuan Wang , Xing Liu , Huan Liu , Jingwei Zhang , Huai Shen , Haiyun Wang","doi":"10.1016/j.expneurol.2025.115328","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Surgery and anesthesia may compromise fragile brain function in the elderly, potentially precipitating cognitive decline or Alzheimer's disease (AD) following perioperative neurocognitive disorder (PND). Vasoactive intestinal peptide (VIP) exhibits anti-inflammatory properties via the gut-brain axis. Nevertheless, whether VIP regulation enhances cognitive function in the fragile brains of aged rat and the underlying mechanisms remain to be elucidated.</div></div><div><h3>Methods</h3><div>A model of fragile brain function was established in elderly rats through bilateral common carotid artery ligation. Cognitive impairment induced by anesthesia and surgery was evaluated using behavioral assays, quantification of cognition-related protein levels, analysis of inflammatory markers, assessment of microglial polarization, and examination of intestinal mucosal and blood-brain barrier integrity. Adeno-associated virus (AAV) was employed to upregulate VIP expression in the colon, and subsequent alterations in the aforementioned parameters were recorded.</div></div><div><h3>Results</h3><div>Cognitive performance was evaluated through behavioral assays, while cognition-related protein levels were determined using Western blot analysis. Anesthesia and surgical interventions exacerbated cognitive deficits in rats with fragile brain function. VIP upregulation significantly ameliorated post-anesthesia and surgery cognitive deficits, normalized cognition-related protein expression, attenuated the inflammatory response, and promoted the repair of both intestinal mucosal and blood-brain barriers.</div></div><div><h3>Conclusion</h3><div>These findings indicate that VIP upregulation mitigates anesthesia- and surgery-induced cognitive impairment and its progression in aged rats with fragile brain function a, primarily by modulating the inflammatory response and preserving the gut and blood-brain barrier integrity. This study offers valuable insights potential preventive strategies against cognitive decline.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"392 ","pages":"Article 115328"},"PeriodicalIF":4.6000,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Overexpression of colonic VIP ameliorates cognitive function and barrier system damage caused by sevoflurane anesthesia and surgery in aged rats with fragile brain functions\",\"authors\":\"Huihui Liao , Xinyi Wang , Chenyi Yang , Zixuan Wang , Xing Liu , Huan Liu , Jingwei Zhang , Huai Shen , Haiyun Wang\",\"doi\":\"10.1016/j.expneurol.2025.115328\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>Surgery and anesthesia may compromise fragile brain function in the elderly, potentially precipitating cognitive decline or Alzheimer's disease (AD) following perioperative neurocognitive disorder (PND). Vasoactive intestinal peptide (VIP) exhibits anti-inflammatory properties via the gut-brain axis. Nevertheless, whether VIP regulation enhances cognitive function in the fragile brains of aged rat and the underlying mechanisms remain to be elucidated.</div></div><div><h3>Methods</h3><div>A model of fragile brain function was established in elderly rats through bilateral common carotid artery ligation. Cognitive impairment induced by anesthesia and surgery was evaluated using behavioral assays, quantification of cognition-related protein levels, analysis of inflammatory markers, assessment of microglial polarization, and examination of intestinal mucosal and blood-brain barrier integrity. Adeno-associated virus (AAV) was employed to upregulate VIP expression in the colon, and subsequent alterations in the aforementioned parameters were recorded.</div></div><div><h3>Results</h3><div>Cognitive performance was evaluated through behavioral assays, while cognition-related protein levels were determined using Western blot analysis. Anesthesia and surgical interventions exacerbated cognitive deficits in rats with fragile brain function. VIP upregulation significantly ameliorated post-anesthesia and surgery cognitive deficits, normalized cognition-related protein expression, attenuated the inflammatory response, and promoted the repair of both intestinal mucosal and blood-brain barriers.</div></div><div><h3>Conclusion</h3><div>These findings indicate that VIP upregulation mitigates anesthesia- and surgery-induced cognitive impairment and its progression in aged rats with fragile brain function a, primarily by modulating the inflammatory response and preserving the gut and blood-brain barrier integrity. This study offers valuable insights potential preventive strategies against cognitive decline.</div></div>\",\"PeriodicalId\":12246,\"journal\":{\"name\":\"Experimental Neurology\",\"volume\":\"392 \",\"pages\":\"Article 115328\"},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2025-05-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Experimental Neurology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S001448862500192X\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Experimental Neurology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S001448862500192X","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}

引用次数: 0

摘要

背景：手术和麻醉可能损害老年人脆弱的脑功能，可能导致围手术期神经认知障碍（PND）后的认知能力下降或阿尔茨海默病（AD）。血管活性肠肽（VIP）通过肠-脑轴表现出抗炎特性。然而，VIP调控是否能增强衰老大鼠脆弱大脑的认知功能及其机制仍有待阐明。方法：采用双侧颈总动脉结扎法建立老年大鼠脆性脑功能模型。通过行为分析、认知相关蛋白水平量化、炎症标志物分析、小胶质细胞极化评估、肠黏膜和血脑屏障完整性检查来评估麻醉和手术引起的认知障碍。利用腺相关病毒（Adeno-associated virus， AAV）上调VIP在结肠中的表达，随后记录上述参数的变化。结果：认知表现通过行为测试评估，认知相关蛋白水平采用Western blot分析。麻醉和手术干预加重了脑功能脆弱大鼠的认知缺陷。VIP上调可显著改善麻醉后和手术后的认知缺陷，使认知相关蛋白表达正常化，减轻炎症反应，促进肠黏膜和血脑屏障的修复。结论：这些研究结果表明，VIP上调主要通过调节炎症反应和保持肠道和血脑屏障的完整性来减轻麻醉和手术诱导的认知障碍及其在脑功能脆弱的老年大鼠中的进展。这项研究为预防认知能力下降提供了有价值的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Overexpression of colonic VIP ameliorates cognitive function and barrier system damage caused by sevoflurane anesthesia and surgery in aged rats with fragile brain functions

查看原文本刊更多论文

Overexpression of colonic VIP ameliorates cognitive function and barrier system damage caused by sevoflurane anesthesia and surgery in aged rats with fragile brain functions

Background

Surgery and anesthesia may compromise fragile brain function in the elderly, potentially precipitating cognitive decline or Alzheimer's disease (AD) following perioperative neurocognitive disorder (PND). Vasoactive intestinal peptide (VIP) exhibits anti-inflammatory properties via the gut-brain axis. Nevertheless, whether VIP regulation enhances cognitive function in the fragile brains of aged rat and the underlying mechanisms remain to be elucidated.

Methods

A model of fragile brain function was established in elderly rats through bilateral common carotid artery ligation. Cognitive impairment induced by anesthesia and surgery was evaluated using behavioral assays, quantification of cognition-related protein levels, analysis of inflammatory markers, assessment of microglial polarization, and examination of intestinal mucosal and blood-brain barrier integrity. Adeno-associated virus (AAV) was employed to upregulate VIP expression in the colon, and subsequent alterations in the aforementioned parameters were recorded.

Results

Cognitive performance was evaluated through behavioral assays, while cognition-related protein levels were determined using Western blot analysis. Anesthesia and surgical interventions exacerbated cognitive deficits in rats with fragile brain function. VIP upregulation significantly ameliorated post-anesthesia and surgery cognitive deficits, normalized cognition-related protein expression, attenuated the inflammatory response, and promoted the repair of both intestinal mucosal and blood-brain barriers.

Conclusion

These findings indicate that VIP upregulation mitigates anesthesia- and surgery-induced cognitive impairment and its progression in aged rats with fragile brain function a, primarily by modulating the inflammatory response and preserving the gut and blood-brain barrier integrity. This study offers valuable insights potential preventive strategies against cognitive decline.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

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.