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经颅近红外激光通过SIRT3/AMPK/Nrf2通路改善老年小鼠术后神经认知障碍

Transcranial near-infrared laser improves postoperative neurocognitive disorder in aged mice SIRT3/AMPK/Nrf2 pathway.

作者信息

Zhong Junying, Zhao Le, Wu Wensi, Chen Jiawei, Yuan Shangyan, Zhang Xiaojun, Wang Zhi

机构信息

Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.

Department of Thoracic Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China.

出版信息

Front Neurosci. 2023 Jan 24;16:1100915. doi: 10.3389/fnins.2022.1100915. eCollection 2022.

Abstract

BACKGROUND

Postoperative neurocognitive disorder (PND) is a common central nervous system (CNS) complication that might increase the morbidity and mortality of elderly patients after anesthesia/surgery. Neuroinflammation, oxidative stress, and synaptic dysfunction are closely related to cognitive dysfunction, an important clinical feature of PND. Transcranial near-infrared laser (TNIL) is regarded as an effective treatment for cognitive-related diseases by improving mitochondrial function and alleviating neuroinflammation and oxidative stress damage.

MATERIALS AND METHODS

Aged male C57BL/6 mice underwent a carotid artery exposure procedure under isoflurane anesthesia. We treated PND-aged mice for three consecutive days (4 h post-operation, 1-laser) with 810 nm continuous wave (CW) laser 18 J/cm at 120 mW/cm. The post-treatment evaluation included behavioral tests, RTq-PCR, immunofluorescence, and Western blot.

RESULTS

The results demonstrated that TNIL improved PND and the levels of synaptic function-associated proteins such as post-synaptic density protein 95 (PSD95), synaptophysin (SYP), and brain-derived neurotrophic factor (BDNF). Besides, neuroinflammatory cytokine levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β as well as microglia activation and oxidative stress damage were attenuated after TNIL treatment in aged mice with PND. Further investigation suggested that TNIL relieved oxidative stress response by activating the SIRT3/AMPK/Nrf2 pathway.

CONCLUSION

Transcranial near-infrared laser improved cognitive impairment in aged mice with PND, which may be a promising therapeutic for PND.

摘要

背景

术后神经认知障碍(PND)是一种常见的中枢神经系统(CNS)并发症,可能会增加老年患者麻醉/手术后的发病率和死亡率。神经炎症、氧化应激和突触功能障碍与认知功能障碍密切相关,认知功能障碍是PND的一个重要临床特征。经颅近红外激光(TNIL)被认为是一种通过改善线粒体功能、减轻神经炎症和氧化应激损伤来治疗认知相关疾病的有效方法。

材料与方法

老年雄性C57BL/6小鼠在异氟烷麻醉下接受颈动脉暴露手术。我们用810nm连续波(CW)激光以120mW/cm的功率、18J/cm的剂量对PND老年小鼠连续治疗三天(术后4小时,每日1次激光照射)。治疗后的评估包括行为测试、RTq-PCR、免疫荧光和蛋白质免疫印迹。

结果

结果表明,TNIL改善了PND以及突触功能相关蛋白的水平,如突触后致密蛋白95(PSD95)、突触素(SYP)和脑源性神经营养因子(BDNF)。此外,在接受TNIL治疗的PND老年小鼠中,肿瘤坏死因子(TNF)-α和白细胞介素(IL)-1β等神经炎症细胞因子水平以及小胶质细胞活化和氧化应激损伤均有所减轻。进一步研究表明,TNIL通过激活SIRT3/AMPK/Nrf2通路减轻氧化应激反应。

结论

经颅近红外激光改善了PND老年小鼠的认知障碍,这可能是一种有前景的PND治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43dd/9904281/ae0eacbfe50b/fnins-16-1100915-g001.jpg

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