Minocycline Attenuates Sevoflurane-Induced Postoperative Cognitive Dysfunction in Aged Mice by Suppressing Hippocampal Apoptosis and the Notch Signaling Pathway-Mediated Neuroinflammation
Postoperative cognitive dysfunction (POCD), an important postoperative neurological complication, is very common and has an elevated incidence in elderly patients. Sevoflurane, an inhaled anesthetic, has been demonstrated to be associated with POCD in both clinical and animal studies. However, how t...
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MDPI AG
2023-03-01
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| author | Junjie Liang Shanshan Han Chao Ye Haimeng Zhu Jiajun Wu Yunjuan Nie Gaoshang Chai Peng Zhao Dengxin Zhang |
| author_facet | Junjie Liang Shanshan Han Chao Ye Haimeng Zhu Jiajun Wu Yunjuan Nie Gaoshang Chai Peng Zhao Dengxin Zhang |
| author_sort | Junjie Liang |
| collection | DOAJ |
| description | Postoperative cognitive dysfunction (POCD), an important postoperative neurological complication, is very common and has an elevated incidence in elderly patients. Sevoflurane, an inhaled anesthetic, has been demonstrated to be associated with POCD in both clinical and animal studies. However, how to prevent POCD remains unclear. Minocycline, a commonly used antibiotic can cross the blood-brain barrier and exert an inhibitory effect on inflammation in the central nervous system. The present work aimed to examine the protective effect and mechanism of minocycline on sevoflurane-induced POCD in aged mice. We found that 3% sevoflurane administered 2 h a day for 3 consecutive days led to cognitive impairment in aged animals. Further investigation revealed that sevoflurane impaired synapse plasticity by causing apoptosis and neuroinflammation and thus induced cognitive dysfunction. However, minocycline pretreatment (50 mg/kg, i.p, 1 h prior to sevoflurane exposure) significantly attenuated learning and memory impairments associated with sevoflurane in aged animals by suppressing apoptosis and neuroinflammation. Moreover, a mechanistic analysis showed that minocycline suppressed sevoflurane-triggered neuroinflammation by inhibiting Notch signaling. Similar results were also obtained in vitro. Collectively, these findings suggested minocycline may be an effective drug for the prevention of sevoflurane-induced POCD in elderly patients. |
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| issn | 2076-3425 |
| language | English |
| last_indexed | 2024-03-11T06:50:26Z |
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| spelling | doaj.art-3bfe9da2422d445dbddc415c448739632023-11-17T10:00:55ZengMDPI AGBrain Sciences2076-34252023-03-0113351210.3390/brainsci13030512Minocycline Attenuates Sevoflurane-Induced Postoperative Cognitive Dysfunction in Aged Mice by Suppressing Hippocampal Apoptosis and the Notch Signaling Pathway-Mediated NeuroinflammationJunjie Liang0Shanshan Han1Chao Ye2Haimeng Zhu3Jiajun Wu4Yunjuan Nie5Gaoshang Chai6Peng Zhao7Dengxin Zhang8Department of Anesthesiology, Wuxi Maternal and Child Health Care Hospital Affiliated to Jiangnan University, Wuxi 214002, ChinaDepartment of Anesthesiology, Wuxi Maternal and Child Health Care Hospital Affiliated to Jiangnan University, Wuxi 214002, ChinaDepartment of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, ChinaDepartment of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, ChinaDepartment of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, ChinaDepartment of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, ChinaDepartment of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, ChinaDepartment of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, ChinaDepartment of Anesthesiology, Wuxi Maternal and Child Health Care Hospital Affiliated to Jiangnan University, Wuxi 214002, ChinaPostoperative cognitive dysfunction (POCD), an important postoperative neurological complication, is very common and has an elevated incidence in elderly patients. Sevoflurane, an inhaled anesthetic, has been demonstrated to be associated with POCD in both clinical and animal studies. However, how to prevent POCD remains unclear. Minocycline, a commonly used antibiotic can cross the blood-brain barrier and exert an inhibitory effect on inflammation in the central nervous system. The present work aimed to examine the protective effect and mechanism of minocycline on sevoflurane-induced POCD in aged mice. We found that 3% sevoflurane administered 2 h a day for 3 consecutive days led to cognitive impairment in aged animals. Further investigation revealed that sevoflurane impaired synapse plasticity by causing apoptosis and neuroinflammation and thus induced cognitive dysfunction. However, minocycline pretreatment (50 mg/kg, i.p, 1 h prior to sevoflurane exposure) significantly attenuated learning and memory impairments associated with sevoflurane in aged animals by suppressing apoptosis and neuroinflammation. Moreover, a mechanistic analysis showed that minocycline suppressed sevoflurane-triggered neuroinflammation by inhibiting Notch signaling. Similar results were also obtained in vitro. Collectively, these findings suggested minocycline may be an effective drug for the prevention of sevoflurane-induced POCD in elderly patients.https://www.mdpi.com/2076-3425/13/3/512POCDsevofluraneminocyclineapoptosisneuroinflammationNotch signaling pathway |
| spellingShingle | Junjie Liang Shanshan Han Chao Ye Haimeng Zhu Jiajun Wu Yunjuan Nie Gaoshang Chai Peng Zhao Dengxin Zhang Minocycline Attenuates Sevoflurane-Induced Postoperative Cognitive Dysfunction in Aged Mice by Suppressing Hippocampal Apoptosis and the Notch Signaling Pathway-Mediated Neuroinflammation Brain Sciences POCD sevoflurane minocycline apoptosis neuroinflammation Notch signaling pathway |
| title | Minocycline Attenuates Sevoflurane-Induced Postoperative Cognitive Dysfunction in Aged Mice by Suppressing Hippocampal Apoptosis and the Notch Signaling Pathway-Mediated Neuroinflammation |
| title_full | Minocycline Attenuates Sevoflurane-Induced Postoperative Cognitive Dysfunction in Aged Mice by Suppressing Hippocampal Apoptosis and the Notch Signaling Pathway-Mediated Neuroinflammation |
| title_fullStr | Minocycline Attenuates Sevoflurane-Induced Postoperative Cognitive Dysfunction in Aged Mice by Suppressing Hippocampal Apoptosis and the Notch Signaling Pathway-Mediated Neuroinflammation |
| title_full_unstemmed | Minocycline Attenuates Sevoflurane-Induced Postoperative Cognitive Dysfunction in Aged Mice by Suppressing Hippocampal Apoptosis and the Notch Signaling Pathway-Mediated Neuroinflammation |
| title_short | Minocycline Attenuates Sevoflurane-Induced Postoperative Cognitive Dysfunction in Aged Mice by Suppressing Hippocampal Apoptosis and the Notch Signaling Pathway-Mediated Neuroinflammation |
| title_sort | minocycline attenuates sevoflurane induced postoperative cognitive dysfunction in aged mice by suppressing hippocampal apoptosis and the notch signaling pathway mediated neuroinflammation |
| topic | POCD sevoflurane minocycline apoptosis neuroinflammation Notch signaling pathway |
| url | https://www.mdpi.com/2076-3425/13/3/512 |
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