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High-concentration sevoflurane exposure in mid-gestation induces apoptosis of neural stem cells in rat offspring.
Neural Regen Res. 2018 Sep; 13(9):1575-1584.NR

Abstract

Sevoflurane is the most commonly used volatile anesthetic during pregnancy. The viability of neural stem cells directly affects the development of the brain. However, it is unknown whether the use of sevoflurane during the second trimester affects the survival of fetal neural stem cells. Therefore, in this study, we investigated whether exposure to sevoflurane in mid-gestation induces apoptosis of neural stem cells and behavioral abnormalities. On gestational day 14, pregnant rats were anesthetized with 2% or 3.5% sevoflurane for 2 hours. The offspring were weaned at 28 days and subjected to the Morris water maze test. The brains were harvested to examine neural stem cell apoptosis by immunofluorescence and to measure Nestin and SOX-2 levels by western blot assay at 6, 24 and 48 hours after anesthesia as well as on postnatal day (P) 0, 14 and 28. Vascular endothelial growth factor (VEGF) and phosphoinositide 3-kinase (PI3K)/AKT pathway protein levels in fetal brain at 6 hours after anesthesia were assessed by western blot assay. Exposure to high-concentration (3.5%) sevoflurane during mid-gestation increased escape latency and path length to the platform, and it reduced the average duration spent in the target quadrant and platform crossing times. At 6, 24 and 48 hours after anesthesia and at P0, P14 and P28, the percentage of Nestin/terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells was increased, but Nestin and SOX-2 protein levels were decreased in the hippocampus of the offspring. At 6 hours after anesthesia, VEGF, PI3K and phospho-AKT (p-AKT) levels were decreased in the fetal brain. These changes were not observed in animals given low-concentration (2%) sevoflurane exposure. Together, our findings indicate that exposure to a high concentration of sevoflurane (3.5%) in mid-gestation decreases VEGF, PI3K and p-AKT protein levels and induces neural stem cell apoptosis, thereby causing learning and memory dysfunction in the offspring.

Authors+Show Affiliations

Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China.Department of Obstetrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China.Department of Neuroendocrine Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning Province, China.Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30127118

Citation

Wang, Yuan, et al. "High-concentration Sevoflurane Exposure in Mid-gestation Induces Apoptosis of Neural Stem Cells in Rat Offspring." Neural Regeneration Research, vol. 13, no. 9, 2018, pp. 1575-1584.
Wang Y, Yin SW, Zhang N, et al. High-concentration sevoflurane exposure in mid-gestation induces apoptosis of neural stem cells in rat offspring. Neural Regen Res. 2018;13(9):1575-1584.
Wang, Y., Yin, S. W., Zhang, N., & Zhao, P. (2018). High-concentration sevoflurane exposure in mid-gestation induces apoptosis of neural stem cells in rat offspring. Neural Regeneration Research, 13(9), 1575-1584. https://doi.org/10.4103/1673-5374.237121
Wang Y, et al. High-concentration Sevoflurane Exposure in Mid-gestation Induces Apoptosis of Neural Stem Cells in Rat Offspring. Neural Regen Res. 2018;13(9):1575-1584. PubMed PMID: 30127118.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - High-concentration sevoflurane exposure in mid-gestation induces apoptosis of neural stem cells in rat offspring. AU - Wang,Yuan, AU - Yin,Shao-Wei, AU - Zhang,Nan, AU - Zhao,Ping, PY - 2018/8/22/entrez PY - 2018/8/22/pubmed PY - 2018/8/22/medline KW - PI3K KW - anesthesia KW - apoptosis KW - developmental neurobiology KW - learning KW - memory KW - nerve regeneration KW - neural regeneration KW - neural stem cells KW - p-AKT KW - sevoflurane KW - vascular endothelial growth factor SP - 1575 EP - 1584 JF - Neural regeneration research JO - Neural Regen Res VL - 13 IS - 9 N2 - Sevoflurane is the most commonly used volatile anesthetic during pregnancy. The viability of neural stem cells directly affects the development of the brain. However, it is unknown whether the use of sevoflurane during the second trimester affects the survival of fetal neural stem cells. Therefore, in this study, we investigated whether exposure to sevoflurane in mid-gestation induces apoptosis of neural stem cells and behavioral abnormalities. On gestational day 14, pregnant rats were anesthetized with 2% or 3.5% sevoflurane for 2 hours. The offspring were weaned at 28 days and subjected to the Morris water maze test. The brains were harvested to examine neural stem cell apoptosis by immunofluorescence and to measure Nestin and SOX-2 levels by western blot assay at 6, 24 and 48 hours after anesthesia as well as on postnatal day (P) 0, 14 and 28. Vascular endothelial growth factor (VEGF) and phosphoinositide 3-kinase (PI3K)/AKT pathway protein levels in fetal brain at 6 hours after anesthesia were assessed by western blot assay. Exposure to high-concentration (3.5%) sevoflurane during mid-gestation increased escape latency and path length to the platform, and it reduced the average duration spent in the target quadrant and platform crossing times. At 6, 24 and 48 hours after anesthesia and at P0, P14 and P28, the percentage of Nestin/terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells was increased, but Nestin and SOX-2 protein levels were decreased in the hippocampus of the offspring. At 6 hours after anesthesia, VEGF, PI3K and phospho-AKT (p-AKT) levels were decreased in the fetal brain. These changes were not observed in animals given low-concentration (2%) sevoflurane exposure. Together, our findings indicate that exposure to a high concentration of sevoflurane (3.5%) in mid-gestation decreases VEGF, PI3K and p-AKT protein levels and induces neural stem cell apoptosis, thereby causing learning and memory dysfunction in the offspring. SN - 1673-5374 UR - https://www.unboundmedicine.com/medline/citation/30127118/High_concentration_sevoflurane_exposure_in_mid_gestation_induces_apoptosis_of_neural_stem_cells_in_rat_offspring_ L2 - http://www.nrronline.org/article.asp?issn=1673-5374;year=2018;volume=13;issue=9;spage=1575;epage=1584;aulast=Wang DB - PRIME DP - Unbound Medicine ER -
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