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Dexmedetomidine mitigates sevoflurane-induced cell cycle arrest in hippocampus

Abstract

Background

Epidemiologic studies suggest the possibility of a modestly elevated risk of adverse neurodevelopmental outcomes in children exposed to anesthesia during early childhood. Sevoflurane is widely used in pediatric anesthetic practice because of its rapid induction and lower pungency. However, it is reported that sevoflurane leads to the long-term cognitive impairment. Some evidence revealed that the selective α2-adrenoreceptor agonist dexmedetomidine (DEX) exerts neuroprotective effects in various brain injury models of animals. But the role of DEX on sevoflurane-induced neuro-damage remains elusive.

Materials and methods

In our study, we isolated the hippocampal neuron cells from newborn neonatal rats and verified the purity of neurons by immunocytochemistry. We employed the flow cytometry and western blot to examine the effect of sevoflurane, DEX and α2-adrenergic receptor antagonist yohimbine on cell cycle distribution.

Results

Immunocytochemistry results showed the purity of neurons > 94%, which provided a good model for neural pharmacology experiments. The exposure of sevoflurane-induced cell cycle arrest at S phase and suppressed the expression of brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB). The addition of DEX suppressed sevoflurane-induced cell cycle arrest and the inhibitory of BDNF and TrkB expression. But the function of DEX was partly blocked by a α2 adrenergic receptor blocker yohimbine.

Conclusion

Sevoflurane suppressed neuron cell proliferation via inhibiting the expression of BDNF and TrkB, and DEX relieved the neurotoxicity induced by sevoflurane via α2 adrenergic receptor. These findings provided new evidence that DEX exerted as a neuroprotective strategy in sevoflurane-induced neuro-damage, and provided new basis for the clinical application of DEX.

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Abbreviations

DEX:

Dexmedetomidine

MAP-2:

Microtubule-associated protein 2

BDNF:

Brain-derived neurotrophic factor

TrkB:

Tyrosine kinase B

MAC:

Minimum alveolar concentration

GFAP:

Glial fibrillary acidic protein

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Correspondence to Zhen-Ming Dong.

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Bo, LJ., Yu, PX., Zhang, FZ. et al. Dexmedetomidine mitigates sevoflurane-induced cell cycle arrest in hippocampus. J Anesth 32, 717–724 (2018). https://doi.org/10.1007/s00540-018-2545-1

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Keywords

  • Anesthetics
  • Sevoflurane
  • Neuroprotection
  • Dexmedetomidine
  • Brain-derived neurotrophic factor-tyrosine kinase B