Repeated lidocaine exposure induces synaptic and cognitive impairment in aged mice by activating microglia and neurotoxic A1 astrocytes
Summary: In the perioperative setting, the administration of intravenous lidocaine is widespread. This study investigates the effects of varying frequencies of intravenous lidocaine on cognitive function in mice of differing ages. Young adult and aged mice received systemic lidocaine either once or...
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| Language: | English |
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Elsevier
2025-03-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225003013 |
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| author | Xiaohui Chen Haiyang Wan Yongxin Huang Andi Chen Xuyang Wu Yanhua Guo Jianjie Wei Pinzhong Chen Jiangdan Jiang Xiaochun Zheng |
| author_facet | Xiaohui Chen Haiyang Wan Yongxin Huang Andi Chen Xuyang Wu Yanhua Guo Jianjie Wei Pinzhong Chen Jiangdan Jiang Xiaochun Zheng |
| author_sort | Xiaohui Chen |
| collection | DOAJ |
| description | Summary: In the perioperative setting, the administration of intravenous lidocaine is widespread. This study investigates the effects of varying frequencies of intravenous lidocaine on cognitive function in mice of differing ages. Young adult and aged mice received systemic lidocaine either once or three times. Our findings indicated that repeated exposure to systemic lidocaine in aged mice resulted in cognitive impairment, accompanied by neuronal apoptosis and synaptic loss in the hippocampus. Additionally, repeated lidocaine exposure activated microglia and neurotoxic A1 astrocytes in aged mice. Notably, the adverse effects were significantly diminished when aged mice were treated with dehydroxymethylepoxyquinomicin (DHMEQ), a specific NF-κB inhibitor. Furthermore, depleting microglia with PLX5622 effectively prevented the activation of A1 astrocytes and synaptic loss following lidocaine exposure. This study provides evidence linking age and exposure frequency to cognitive impairment due to systemic lidocaine administration, correlating with the activation of microglia and neurotoxic A1 astrocytes. |
| format | Article |
| id | doaj-art-3e9bc22d0434466193bce680f6a31200 |
| institution | DOAJ |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-3e9bc22d0434466193bce680f6a312002025-08-20T02:45:18ZengElsevieriScience2589-00422025-03-0128311204110.1016/j.isci.2025.112041Repeated lidocaine exposure induces synaptic and cognitive impairment in aged mice by activating microglia and neurotoxic A1 astrocytesXiaohui Chen0Haiyang Wan1Yongxin Huang2Andi Chen3Xuyang Wu4Yanhua Guo5Jianjie Wei6Pinzhong Chen7Jiangdan Jiang8Xiaochun Zheng9Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, China; Corresponding authorDepartment of Anesthesiology, First Affiliated Hospital of Yangtze University, First People’s Hospital of Jingzhou, Jingzhou, ChinaDepartment of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, ChinaDepartment of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, ChinaDepartment of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, ChinaDepartment of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, ChinaDepartment of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, ChinaDepartment of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, ChinaDepartment of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, ChinaDepartment of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, China; Fujian Emergency Medical Center, Fujian Provincial Key Laboratory of Critical Care Medicine, Fujian Provincial Co-Constructed Laboratory of “Belt and Road”, Fuzhou, China; Corresponding authorSummary: In the perioperative setting, the administration of intravenous lidocaine is widespread. This study investigates the effects of varying frequencies of intravenous lidocaine on cognitive function in mice of differing ages. Young adult and aged mice received systemic lidocaine either once or three times. Our findings indicated that repeated exposure to systemic lidocaine in aged mice resulted in cognitive impairment, accompanied by neuronal apoptosis and synaptic loss in the hippocampus. Additionally, repeated lidocaine exposure activated microglia and neurotoxic A1 astrocytes in aged mice. Notably, the adverse effects were significantly diminished when aged mice were treated with dehydroxymethylepoxyquinomicin (DHMEQ), a specific NF-κB inhibitor. Furthermore, depleting microglia with PLX5622 effectively prevented the activation of A1 astrocytes and synaptic loss following lidocaine exposure. This study provides evidence linking age and exposure frequency to cognitive impairment due to systemic lidocaine administration, correlating with the activation of microglia and neurotoxic A1 astrocytes.http://www.sciencedirect.com/science/article/pii/S2589004225003013PharmacologyNeuroscienceImmunologyCell biology |
| spellingShingle | Xiaohui Chen Haiyang Wan Yongxin Huang Andi Chen Xuyang Wu Yanhua Guo Jianjie Wei Pinzhong Chen Jiangdan Jiang Xiaochun Zheng Repeated lidocaine exposure induces synaptic and cognitive impairment in aged mice by activating microglia and neurotoxic A1 astrocytes iScience Pharmacology Neuroscience Immunology Cell biology |
| title | Repeated lidocaine exposure induces synaptic and cognitive impairment in aged mice by activating microglia and neurotoxic A1 astrocytes |
| title_full | Repeated lidocaine exposure induces synaptic and cognitive impairment in aged mice by activating microglia and neurotoxic A1 astrocytes |
| title_fullStr | Repeated lidocaine exposure induces synaptic and cognitive impairment in aged mice by activating microglia and neurotoxic A1 astrocytes |
| title_full_unstemmed | Repeated lidocaine exposure induces synaptic and cognitive impairment in aged mice by activating microglia and neurotoxic A1 astrocytes |
| title_short | Repeated lidocaine exposure induces synaptic and cognitive impairment in aged mice by activating microglia and neurotoxic A1 astrocytes |
| title_sort | repeated lidocaine exposure induces synaptic and cognitive impairment in aged mice by activating microglia and neurotoxic a1 astrocytes |
| topic | Pharmacology Neuroscience Immunology Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225003013 |
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