2. Academic Validation
  3. Disruption of the GABAergic system contributes to the development of perioperative neurocognitive disorders after anesthesia and surgery in aged mice

Disruption of the GABAergic system contributes to the development of perioperative neurocognitive disorders after anesthesia and surgery in aged mice

  • CNS Neurosci Ther. 2020 Sep;26(9):913-924. doi: 10.1111/cns.13388.
Wen Zhang 1,  Bing-Rui Xiong 2,  Long-Qing Zhang 1,  Xian Huang 3,  Wen-Chang Zhou 1,  Qian Zou 4,  Anne Manyande 5,  Jie Wang 6,  Xue-Bi Tian 1,  Yu-Ke Tian 1
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 2 Department of Anesthesiology, Zhongnan Hospital, Wuhan University, Wuhan, China.
  • 3 Department of Physiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 4 Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 5 School of Human and Social Sciences, University of West London, London, United Kingdom.
  • 6 State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Key Laboratory of Magnetic Resonance in Biological Systems, Wuhan Center for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, China.
PMID: 32488976 DOI: 10.1111/cns.13388
Abstract

Aims: Perioperative neurocognitive disorders (PND) are associated with cognitive impairment in the preoperative or postoperative period, and neuroinflammation is thought to be the most important mechanisms especially during the postoperative period. The GABAergic system is easily disrupted by neuroinflammation. This study investigated the impact of the GABAergic system on PND after anesthesia and surgery.

Methods: An animal model of laparotomy with inhalation anesthesia in 16-month-old mice was addressed. Effects of the GABAergic system were assessed using biochemical analysis. Pharmacological blocking of α5GABAA Rs or P38 mitogen-activated protein kinase (MAPK) were applied to investigate the effects of the GABAergic system.

Results: After laparotomy, the hippocampus-dependent memory and long-term potentiation were impaired, the levels of IL-6, IL-1β and TNF-α up-regulated in the hippocampus, the concentration of GABA decreased, and the protein levels of the surface α5GABAA Rs up-regulated. Pharmacological blocking of α5GABAA Rs with L655,708 alleviated laparotomy induced cognitive deficits. Further studies found that the p38 MAPK signaling pathway was involved and pharmacological blocking with SB203,580 alleviated memory dysfunctions.

Conclusions: Anesthesia and surgery caused neuroinflammation in the hippocampus, which consequently disrupted the GABAergic system, increased the expressions of surface α5GABAA Rs especially through the p38 MAPK signaling pathway, and eventually led to hippocampus-dependent memory dysfunctions.

Keywords

GABAergic system; mitogen-activated protein kinase; neuroinflammation; perioperative neurocognitive disorders; α5GABAA receptors.

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