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Sevoflurane anesthesia in pregnant mice induces neurotoxicity in fetal and offspring mice.
Anesthesiology. 2013 Mar; 118(3):516-26.A

Abstract

BACKGROUND

Each year, over 75,000 pregnant women in the United States undergo anesthesia care. The authors set out to assess the effects of the anesthetic sevoflurane on neurotoxicity in pregnant mice and on learning and memory in fetal and offspring mice.

METHODS

Pregnant mice (gestational day 14) and mouse primary neurons were treated with 2.5% sevoflurane for 2 h and 4.1% sevoflurane for 6 h, respectively. Brain tissues of both fetal and offspring mice (P31) and the primary neurons were harvested and subjected to Western blot and immunohistochemistry to assess interleukin-6, the synaptic markers postsynaptic density-95 and synaptophysin, and caspase-3 levels. Separately, learning and memory function in the offspring mice was determined in the Morris water maze.

RESULTS

Sevoflurane anesthesia in pregnant mice induced caspase-3 activation, increased interleukin-6 levels (256 ± 50.98% [mean ± SD] vs. 100 ± 54.12%, P = 0.026), and reduced postsynaptic density-95 (61 ± 13.53% vs. 100 ± 10.08%, P = 0.036) and synaptophysin levels in fetal and offspring mice. The sevoflurane anesthesia impaired learning and memory in offspring mice at P31. Moreover, interleukin-6 antibody mitigated the sevoflurane-induced reduction in postsynaptic density-95 levels in the neurons. Finally, environmental enrichment attenuated the sevoflurane-induced increases in interleukin-6 levels, reductions of synapse markers, and learning and memory impairment.

CONCLUSIONS

These results suggest that sevoflurane may induce detrimental effects in fetal and offspring mice, which can be mitigated by environmental enrichment. These findings should promote more studies to determine the neurotoxicity of anesthesia in the developing brain.

Authors+Show Affiliations

Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23314109

Citation

Zheng, Hui, et al. "Sevoflurane Anesthesia in Pregnant Mice Induces Neurotoxicity in Fetal and Offspring Mice." Anesthesiology, vol. 118, no. 3, 2013, pp. 516-26.
Zheng H, Dong Y, Xu Z, et al. Sevoflurane anesthesia in pregnant mice induces neurotoxicity in fetal and offspring mice. Anesthesiology. 2013;118(3):516-26.
Zheng, H., Dong, Y., Xu, Z., Crosby, G., Culley, D. J., Zhang, Y., & Xie, Z. (2013). Sevoflurane anesthesia in pregnant mice induces neurotoxicity in fetal and offspring mice. Anesthesiology, 118(3), 516-26. https://doi.org/10.1097/ALN.0b013e3182834d5d
Zheng H, et al. Sevoflurane Anesthesia in Pregnant Mice Induces Neurotoxicity in Fetal and Offspring Mice. Anesthesiology. 2013;118(3):516-26. PubMed PMID: 23314109.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sevoflurane anesthesia in pregnant mice induces neurotoxicity in fetal and offspring mice. AU - Zheng,Hui, AU - Dong,Yuanlin, AU - Xu,Zhipeng, AU - Crosby,Gregory, AU - Culley,Deborah J, AU - Zhang,Yiying, AU - Xie,Zhongcong, PY - 2013/1/15/entrez PY - 2013/1/15/pubmed PY - 2013/4/23/medline SP - 516 EP - 26 JF - Anesthesiology JO - Anesthesiology VL - 118 IS - 3 N2 - BACKGROUND: Each year, over 75,000 pregnant women in the United States undergo anesthesia care. The authors set out to assess the effects of the anesthetic sevoflurane on neurotoxicity in pregnant mice and on learning and memory in fetal and offspring mice. METHODS: Pregnant mice (gestational day 14) and mouse primary neurons were treated with 2.5% sevoflurane for 2 h and 4.1% sevoflurane for 6 h, respectively. Brain tissues of both fetal and offspring mice (P31) and the primary neurons were harvested and subjected to Western blot and immunohistochemistry to assess interleukin-6, the synaptic markers postsynaptic density-95 and synaptophysin, and caspase-3 levels. Separately, learning and memory function in the offspring mice was determined in the Morris water maze. RESULTS: Sevoflurane anesthesia in pregnant mice induced caspase-3 activation, increased interleukin-6 levels (256 ± 50.98% [mean ± SD] vs. 100 ± 54.12%, P = 0.026), and reduced postsynaptic density-95 (61 ± 13.53% vs. 100 ± 10.08%, P = 0.036) and synaptophysin levels in fetal and offspring mice. The sevoflurane anesthesia impaired learning and memory in offspring mice at P31. Moreover, interleukin-6 antibody mitigated the sevoflurane-induced reduction in postsynaptic density-95 levels in the neurons. Finally, environmental enrichment attenuated the sevoflurane-induced increases in interleukin-6 levels, reductions of synapse markers, and learning and memory impairment. CONCLUSIONS: These results suggest that sevoflurane may induce detrimental effects in fetal and offspring mice, which can be mitigated by environmental enrichment. These findings should promote more studies to determine the neurotoxicity of anesthesia in the developing brain. SN - 1528-1175 UR - https://www.unboundmedicine.com/medline/citation/23314109/Sevoflurane_anesthesia_in_pregnant_mice_induces_neurotoxicity_in_fetal_and_offspring_mice_ L2 - http://anesthesiology.pubs.asahq.org/article.aspx?doi=10.1097/ALN.0b013e3182834d5d DB - PRIME DP - Unbound Medicine ER -