Tags

Type your tag names separated by a space and hit enter

Subsequent maternal separation exacerbates neurobehavioral abnormalities in rats neonatally exposed to sevoflurane anesthesia.
Neurosci Lett. 2017 Nov 20; 661:137-142.NL

Abstract

Several recent studies suggest that in the human population, a routine, short anesthetic in otherwise healthy infants is void of neurodevelopmental insult. On the other hand, many human retrospective epidemiological studies report evidence of cognitive abnormalities in children after testing those who had different anesthesia-requiring procedures in early childhood. We tested in a rat model whether post-anesthesia stressful environmental factors can contribute to developmental abnormalities that were initiated by a relatively short exposure to sevoflurane, the most widely used anesthetic in pediatric anesthesia, whose polyvalent actions include enhancement of gamma-aminobutyric acid type A receptor (GABAAR) activity. Postnatal day 6 (P6) male Sprague-Dawley rats were anesthetized with sevoflurane for 60min. To simulate subsequent stress, the animals were subjected to a single maternal separation for 180min at P10. To study the role of GABAAR-mediated depolarization, subgroups of P6 rats received a single injection of the Na+-K+-2Cl- (NKCC1) inhibitor, bumetanide, prior to initiation of anesthesia with sevoflurane. Rats that were exposed to sevoflurane had decreased hypothalamic K+-2Cl- (KCC2) mRNA level (F(2,13)=3.839, P=0.049), increased NKCC1/KCC2 mRNA ratio (F(2,13)=5.043, P=0.024) and increased corticotropin-releasing hormone (CRH) mRNA level (F(2,12)=9.450, P=0.003) at P10, the age at which maternal separation was imposed. Adult rats, neonatally exposed to a combination of sevoflurane and maternal separation, exhibited increases in the escape latencies greater than animals exposed to sevoflurane only (P=0.012), and only rats in the sevoflurane plus maternal separation group spent significantly less time in the target quadrant during the Morris water maze test (F(4,55)=4.856, P=0.002). Bumetanide ameliorated abnormalities induced by sevoflurane and a combination of sevoflurane plus maternal separation. Neonatal exposure to sevoflurane may sensitize to stressors later in life, and post-exposure stress may exacerbate neurodevelopmental abnormalities even after a relatively short exposure to sevoflurane in rodents. The NKCC1 downregulation prior to exposure to the anesthetic may be therapeutic.

Authors+Show Affiliations

Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China; Department of Anesthesiology, University of Florida College of Medicine, Gainesville, FL, United States; Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China; Department of Anesthesiology, University of Florida College of Medicine, Gainesville, FL, United States; Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China; Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China; Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China; Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China; Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China. Electronic address: yjyangjj@126.com.Department of Anesthesiology, University of Florida College of Medicine, Gainesville, FL, United States; McKnight Brain Institute, University of FL College of Medicine, Gainesville, FL, United States. Electronic address: amartynyuk@anest.ufl.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28982596

Citation

Yang, Jiaojiao, et al. "Subsequent Maternal Separation Exacerbates Neurobehavioral Abnormalities in Rats Neonatally Exposed to Sevoflurane Anesthesia." Neuroscience Letters, vol. 661, 2017, pp. 137-142.
Yang J, Ju L, Jia M, et al. Subsequent maternal separation exacerbates neurobehavioral abnormalities in rats neonatally exposed to sevoflurane anesthesia. Neurosci Lett. 2017;661:137-142.
Yang, J., Ju, L., Jia, M., Zhang, H., Sun, X., Ji, M., Yang, J., & Martynyuk, A. E. (2017). Subsequent maternal separation exacerbates neurobehavioral abnormalities in rats neonatally exposed to sevoflurane anesthesia. Neuroscience Letters, 661, 137-142. https://doi.org/10.1016/j.neulet.2017.09.063
Yang J, et al. Subsequent Maternal Separation Exacerbates Neurobehavioral Abnormalities in Rats Neonatally Exposed to Sevoflurane Anesthesia. Neurosci Lett. 2017 Nov 20;661:137-142. PubMed PMID: 28982596.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Subsequent maternal separation exacerbates neurobehavioral abnormalities in rats neonatally exposed to sevoflurane anesthesia. AU - Yang,Jiaojiao, AU - Ju,Lingsha, AU - Jia,Min, AU - Zhang,Hui, AU - Sun,Xiaoru, AU - Ji,Muhuo, AU - Yang,Jianjun, AU - Martynyuk,Anatoly E, Y1 - 2017/10/02/ PY - 2017/03/10/received PY - 2017/09/24/revised PY - 2017/09/29/accepted PY - 2017/10/7/pubmed PY - 2018/7/27/medline PY - 2017/10/7/entrez KW - Developing brain KW - Environmental factor KW - NKCC1/KCC2 KW - Neurobehavioral abnormalities KW - Sevoflurane KW - Stress SP - 137 EP - 142 JF - Neuroscience letters JO - Neurosci. Lett. VL - 661 N2 - Several recent studies suggest that in the human population, a routine, short anesthetic in otherwise healthy infants is void of neurodevelopmental insult. On the other hand, many human retrospective epidemiological studies report evidence of cognitive abnormalities in children after testing those who had different anesthesia-requiring procedures in early childhood. We tested in a rat model whether post-anesthesia stressful environmental factors can contribute to developmental abnormalities that were initiated by a relatively short exposure to sevoflurane, the most widely used anesthetic in pediatric anesthesia, whose polyvalent actions include enhancement of gamma-aminobutyric acid type A receptor (GABAAR) activity. Postnatal day 6 (P6) male Sprague-Dawley rats were anesthetized with sevoflurane for 60min. To simulate subsequent stress, the animals were subjected to a single maternal separation for 180min at P10. To study the role of GABAAR-mediated depolarization, subgroups of P6 rats received a single injection of the Na+-K+-2Cl- (NKCC1) inhibitor, bumetanide, prior to initiation of anesthesia with sevoflurane. Rats that were exposed to sevoflurane had decreased hypothalamic K+-2Cl- (KCC2) mRNA level (F(2,13)=3.839, P=0.049), increased NKCC1/KCC2 mRNA ratio (F(2,13)=5.043, P=0.024) and increased corticotropin-releasing hormone (CRH) mRNA level (F(2,12)=9.450, P=0.003) at P10, the age at which maternal separation was imposed. Adult rats, neonatally exposed to a combination of sevoflurane and maternal separation, exhibited increases in the escape latencies greater than animals exposed to sevoflurane only (P=0.012), and only rats in the sevoflurane plus maternal separation group spent significantly less time in the target quadrant during the Morris water maze test (F(4,55)=4.856, P=0.002). Bumetanide ameliorated abnormalities induced by sevoflurane and a combination of sevoflurane plus maternal separation. Neonatal exposure to sevoflurane may sensitize to stressors later in life, and post-exposure stress may exacerbate neurodevelopmental abnormalities even after a relatively short exposure to sevoflurane in rodents. The NKCC1 downregulation prior to exposure to the anesthetic may be therapeutic. SN - 1872-7972 UR - https://www.unboundmedicine.com/medline/citation/28982596/Subsequent_maternal_separation_exacerbates_neurobehavioral_abnormalities_in_rats_neonatally_exposed_to_sevoflurane_anesthesia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(17)30815-7 DB - PRIME DP - Unbound Medicine ER -