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Sevoflurane induces neurotoxic effects on developing neurons through the WNK1/NKCC1/Ca2+ /Drp-1 signalling pathway

Ya-Fan Bai1, Wen-Jing Li1, Yu-Wei Ji1

  • 1Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

Clinical and Experimental Pharmacology & Physiology
|February 3, 2023
PubMed

Insights

Sevoflurane anesthesia harms brain cells by disrupting the WNK1/NKCC1/Ca2+/Drp-1 pathway, leading to cell death. Inhibiting this pathway may protect against anesthesia-induced neurotoxicity in children.

Area of Science:

  • Neuroscience
  • Anesthesiology
  • Cell Biology

Background:

  • Repeated anesthesia exposure in children poses a risk for cognitive impairment.
  • The precise mechanisms underlying anesthesia-induced neurotoxicity remain unclear.

Purpose of the Study:

  • To investigate the neurotoxic mechanism of sevoflurane anesthesia.
  • To explore the role of the WNK1/NKCC1/Ca2+/Drp-1 signaling pathway in sevoflurane neurotoxicity.

Main Methods:

  • Utilized the HT22 hippocampal neuronal cell line.
  • Treated cells with sevoflurane anesthesia (4.1% for 6 hours).
  • Administered WNK1, CaN, and Drp-1 inhibitors (WNK-463, FK506, Mdivi-1) prior to sevoflurane exposure.

Main Results:

  • Sevoflurane decreased cell viability and increased apoptosis.
  • Inhibitors WNK-463, FK506, and Mdivi-1 alleviated sevoflurane-induced cell damage and apoptosis.
  • Sevoflurane increased WNK1 kinase and NKCC1 protein levels, intracellular calcium, and CaN expression, while decreasing Drp-1 phosphorylation.
  • FK506 pretreatment reduced Drp-1 dephosphorylation.

Conclusions:

  • The WNK1/NKCC1/Ca2+/Drp-1 pathway is crucial in sevoflurane-induced neurotoxicity.
  • Reducing intracellular calcium influx is a potential strategy to mitigate sevoflurane neurotoxicity.

Keywords:
WNK1/NKCC1/Ca2+/Drp-1 signalling pathwaymitochondrial dynamicsneurotoxicitysevoflurane

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