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  3. Repeated lidocaine exposure induces synaptic and cognitive impairment in aged mice by activating microglia and neurotoxic A1 astrocytes

Repeated lidocaine exposure induces synaptic and cognitive impairment in aged mice by activating microglia and neurotoxic A1 astrocytes

  • iScience. 2025 Feb 17;28(3):112041. doi: 10.1016/j.isci.2025.112041.
Xiaohui Chen 1,  Haiyang Wan 2,  Yongxin Huang 1,  Andi Chen 1,  Xuyang Wu 1,  Yanhua Guo 1,  Jianjie Wei 1,  Pinzhong Chen 1,  Jiangdan Jiang 1,  Xiaochun Zheng 1 3
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, China.
  • 2 Department of Anesthesiology, First Affiliated Hospital of Yangtze University, First People's Hospital of Jingzhou, Jingzhou, China.
  • 3 Fujian Emergency Medical Center, Fujian Provincial Key Laboratory of Critical Care Medicine, Fujian Provincial Co-Constructed Laboratory of "Belt and Road", Fuzhou, China.
PMID: 40092614 DOI: 10.1016/j.isci.2025.112041
Abstract

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.

Keywords

Cell biology; Immunology; Neuroscience; Pharmacology.

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