Open Access

Ketamine administration ameliorates anesthesia and surgery‑induced cognitive dysfunction via activation of TRPV4 channel opening

  • Authors:
    • Qi Li
    • Dong-Na Zhou
    • Yi-Qing Tu
    • Xin-Wei Wu
    • Da-Qing Pei
    • Yun Xiong
  • View Affiliations

  • Published online on: June 1, 2022     https://doi.org/10.3892/etm.2022.11405
  • Article Number: 478
  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Perioperative neurocognitive disorder (PND) is a common complication associated with anesthesia and surgery in the elderly. The dysfunction of transient receptor potential vanilloid 4 (TRPV4) has been associated with a number of diseases, including Alzheimer's disease. Given that ketamine can reportedly improve PNDs, the present study sought to determine whether ketamine‑induced PND alleviation was mediated by activation of TRPV4 channel opening. A total of 120, 20‑month‑old male C57BL/6 mice were randomly divided into five groups: Vehicle, PND (tibial fracture surgery), PND + ketamine (Ket), PND + Ket + HC‑067047 (HC), and PND + HC groups. Ketamine (0.5 mg/kg) was administered intraperitoneally once a day for 3 days after surgery and HC‑067047 (1 µmol/2 µl), an antagonist of TRPV4, was administered via the left lateral ventricle 30 min before ketamine treatment. Superoxide dismutase (SOD), malondialdehyde (MDA), lipid peroxidation (LPO), IL‑1β, IL‑6, adenosine monophosphate‑activated protein kinase (AMPK), NF‑κB, TNF‑α and IFN‑β levels were determined 3 days after surgery. At 28 days after surgery, fear conditioning and novel object recognition were assessed, and Aβ1‑42 levels were measured and ionized calcium binding adaptor molecule 1 (Iba1) staining was conducted on day 31 after surgery. The results revealed that ketamine administration upregulated total SOD activity, downregulated MDA and LPO content, mitigated phosphorylated (p)‑NF‑κB, TNF‑α mRNA and IFN‑β mRNA expression in the hippocampus, and promoted p‑AMPK 3 days after surgery. Furthermore, it was found that ketamine increased both context‑ and tone‑dependent fear conditioning, and the time spent exploring a novel object, and reduced Aβ peptide levels and microglial activation 30 days after surgery. Notably, these changes could be reversed by HC‑067047 to a certain extent. In conclusion, ketamine improved PND in aged mice after tibial fracture surgery and the potential mechanism may involve activation of the TRPV4/AMPK/NF‑κB signaling pathway.
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July-2022
Volume 24 Issue 1

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Copy and paste a formatted citation
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Spandidos Publications style
Li Q, Zhou D, Tu Y, Wu X, Pei D and Xiong Y: Ketamine administration ameliorates anesthesia and surgery‑induced cognitive dysfunction via activation of TRPV4 channel opening. Exp Ther Med 24: 478, 2022
APA
Li, Q., Zhou, D., Tu, Y., Wu, X., Pei, D., & Xiong, Y. (2022). Ketamine administration ameliorates anesthesia and surgery‑induced cognitive dysfunction via activation of TRPV4 channel opening. Experimental and Therapeutic Medicine, 24, 478. https://doi.org/10.3892/etm.2022.11405
MLA
Li, Q., Zhou, D., Tu, Y., Wu, X., Pei, D., Xiong, Y."Ketamine administration ameliorates anesthesia and surgery‑induced cognitive dysfunction via activation of TRPV4 channel opening". Experimental and Therapeutic Medicine 24.1 (2022): 478.
Chicago
Li, Q., Zhou, D., Tu, Y., Wu, X., Pei, D., Xiong, Y."Ketamine administration ameliorates anesthesia and surgery‑induced cognitive dysfunction via activation of TRPV4 channel opening". Experimental and Therapeutic Medicine 24, no. 1 (2022): 478. https://doi.org/10.3892/etm.2022.11405