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Repeated 2% sevoflurane administration in 7‑ and 60-day-old rats : Neurotoxicity and neurocognitive dysfunction.
Anaesthesist. 2017 Nov; 66(11):850-857.A

Abstract

BACKGROUND

Sevoflurane is one of the most widely used inhalation anesthetics in pediatric anesthesia. A large number of studies have demonstrated that repeated treatment with high concentrations or long durations of sevoflurane anesthesia during the neonatal period can induce neuroapoptosis and long-term learning disability. In clinical practice, we observed that a subset of patients underwent minor surgery under sevoflurane anesthesia more than once from birth to adolescence. Therefore, this research was conducted to investigate whether a 2% concentration of sevoflurane (clinically relevant usage of sevoflurane) for 1 h (a short duration) can induce neuroapoptosis and neurocognitive dysfunction in adolescent rats that received sevoflurane (2% for 1 h) during the neonatal period.

MATERIAL AND METHODS

Group I: neonatal rats at postnatal day 7 (PND-7) were treated with oxygen under controlled conditions and then raised to PND-60. Group II: PND-7 rats were treated with 2% sevoflurane for 1 h and then raised to PND-60. Group III: the PND-60 rats were treated with 2% sevoflurane for 1 h and in group IV the PND-7 rats were treated with 2% sevoflurane for 1 h and then anesthetized with 2% sevoflurane for 1 h at PND-60 again. The expression of caspase-3, Bax and Bcl-2 in the hippocampal dentate gyrus (DG) were measured by Western blot analysis. Neuroapoptosis in the hippocampal DG was assessed using NeuN/caspase-3 double-immunofluorescence staining. Spatial reference memory was tested by the Morris water maze test.

RESULTS

The present data showed that sevoflurane (2% for 1 h) did not induce obvious hippocampal neuroapoptosis in the PND-7 rats and PND-60 rats; their performance in hippocampal-dependent spatial memory was not significantly impaired; however, the rats in group IV showed poor performance in the Morris water maze test and the neuroapoptosis in group IV was significantly increased.

CONCLUSION

Our findings suggested that sevoflurane can induce neuroapoptosis and cognitive dysfunction in adolescent rats that received repeated sevoflurane (2% for 1 h) during the postnatal period. These findings will promote further studies to investigate the effects of repeated sevoflurane exposure on the development of the central nervous system and function of learning and memory, as well as the underlying mechanisms in vitro and in vivo.

Authors+Show Affiliations

Department of Anesthesiology, The First Affiliated Hospital with Nanjing Medical University, Guangzhou Road 300, 210029, Nanjing, China.Department of Anesthesiology, The First Affiliated Hospital with Nanjing Medical University, Guangzhou Road 300, 210029, Nanjing, China.Department of Anesthesiology, The First Affiliated Hospital with Nanjing Medical University, Guangzhou Road 300, 210029, Nanjing, China.Department of Anesthesiology, The First Affiliated Hospital with Nanjing Medical University, Guangzhou Road 300, 210029, Nanjing, China.Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, China.Department of Anesthesiology, The First Affiliated Hospital with Nanjing Medical University, Guangzhou Road 300, 210029, Nanjing, China. hh19871117@126.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28914327

Citation

Huang, He, et al. "Repeated 2% Sevoflurane Administration in 7‑ and 60-day-old Rats : Neurotoxicity and Neurocognitive Dysfunction." Der Anaesthesist, vol. 66, no. 11, 2017, pp. 850-857.
Huang H, Liu CM, Sun J, et al. Repeated 2% sevoflurane administration in 7‑ and 60-day-old rats : Neurotoxicity and neurocognitive dysfunction. Anaesthesist. 2017;66(11):850-857.
Huang, H., Liu, C. M., Sun, J., Jin, W. J., Wu, Y. Q., & Chen, J. (2017). Repeated 2% sevoflurane administration in 7‑ and 60-day-old rats : Neurotoxicity and neurocognitive dysfunction. Der Anaesthesist, 66(11), 850-857. https://doi.org/10.1007/s00101-017-0359-4
Huang H, et al. Repeated 2% Sevoflurane Administration in 7‑ and 60-day-old Rats : Neurotoxicity and Neurocognitive Dysfunction. Anaesthesist. 2017;66(11):850-857. PubMed PMID: 28914327.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Repeated 2% sevoflurane administration in 7‑ and 60-day-old rats : Neurotoxicity and neurocognitive dysfunction. AU - Huang,He, AU - Liu,Cun-Ming, AU - Sun,Jie, AU - Jin,Wen-Jie, AU - Wu,Yu-Qing, AU - Chen,Jing, Y1 - 2017/09/15/ PY - 2017/04/17/received PY - 2017/08/04/accepted PY - 2017/08/03/revised PY - 2017/9/16/pubmed PY - 2018/6/28/medline PY - 2017/9/16/entrez KW - Adolescent KW - Neonatal KW - Neurocognitive function KW - Neurotoxicity KW - Sevoflurane SP - 850 EP - 857 JF - Der Anaesthesist JO - Anaesthesist VL - 66 IS - 11 N2 - BACKGROUND: Sevoflurane is one of the most widely used inhalation anesthetics in pediatric anesthesia. A large number of studies have demonstrated that repeated treatment with high concentrations or long durations of sevoflurane anesthesia during the neonatal period can induce neuroapoptosis and long-term learning disability. In clinical practice, we observed that a subset of patients underwent minor surgery under sevoflurane anesthesia more than once from birth to adolescence. Therefore, this research was conducted to investigate whether a 2% concentration of sevoflurane (clinically relevant usage of sevoflurane) for 1 h (a short duration) can induce neuroapoptosis and neurocognitive dysfunction in adolescent rats that received sevoflurane (2% for 1 h) during the neonatal period. MATERIAL AND METHODS: Group I: neonatal rats at postnatal day 7 (PND-7) were treated with oxygen under controlled conditions and then raised to PND-60. Group II: PND-7 rats were treated with 2% sevoflurane for 1 h and then raised to PND-60. Group III: the PND-60 rats were treated with 2% sevoflurane for 1 h and in group IV the PND-7 rats were treated with 2% sevoflurane for 1 h and then anesthetized with 2% sevoflurane for 1 h at PND-60 again. The expression of caspase-3, Bax and Bcl-2 in the hippocampal dentate gyrus (DG) were measured by Western blot analysis. Neuroapoptosis in the hippocampal DG was assessed using NeuN/caspase-3 double-immunofluorescence staining. Spatial reference memory was tested by the Morris water maze test. RESULTS: The present data showed that sevoflurane (2% for 1 h) did not induce obvious hippocampal neuroapoptosis in the PND-7 rats and PND-60 rats; their performance in hippocampal-dependent spatial memory was not significantly impaired; however, the rats in group IV showed poor performance in the Morris water maze test and the neuroapoptosis in group IV was significantly increased. CONCLUSION: Our findings suggested that sevoflurane can induce neuroapoptosis and cognitive dysfunction in adolescent rats that received repeated sevoflurane (2% for 1 h) during the postnatal period. These findings will promote further studies to investigate the effects of repeated sevoflurane exposure on the development of the central nervous system and function of learning and memory, as well as the underlying mechanisms in vitro and in vivo. SN - 1432-055X UR - https://www.unboundmedicine.com/medline/citation/28914327/Repeated_2_sevoflurane_administration_in_7‑_and_60_day_old_rats_:_Neurotoxicity_and_neurocognitive_dysfunction_ L2 - https://dx.doi.org/10.1007/s00101-017-0359-4 DB - PRIME DP - Unbound Medicine ER -