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Anesthesia with sevoflurane in neonatal rats: Developmental neuroendocrine abnormalities and alleviating effects of the corticosteroid and Cl(-) importer antagonists.
Psychoneuroendocrinology. 2015 Oct; 60:173-81.P

Abstract

BACKGROUND

1.5 million children under 12 months of age are exposed to general anesthesia annually in the United States alone. Human and especially animal studies provide evidence that exposure to general anesthesia during the early postnatal period may lead to long-term neurocognitive abnormalities via poorly understood mechanisms. We investigated whether an immature stress response system and γ-aminobutyric acid (GABA) type A receptor activities are involved in mediating these abnormalities.

METHODS

Sprague-Dawley rats at postnatal days 4, 5 or 6 were anesthetized with 2.1% sevoflurane for 6h; maternally separated and house reared rats served as controls.

RESULTS

Sevoflurane anesthesia markedly increased corticosterone levels in rat pups of both genders. In adulthood, these rats responded to stress with heightened secretion of corticosterone and a greater increase in corticosterone levels in males versus females. Only male rats, previously exposed to neonatal sevoflurane, had a higher frequency of miniature inhibitory postsynaptic currents in CA1 neurons, spent a shorter time in open arms of the elevated plus maze (EPM) and exhibited impaired prepulse inhibition (PPI) of startle. Pretreatment of male rats prior to sevoflurane with the Na(+)-K(+)-2Cl(-) cotransporter inhibitor, bumetanide, or the mineralocorticoid receptor antagonist, RU28318, normalized endocrine responses to stress and the EPM behavior in adulthood, while only those pretreated with bumetanide exhibited normalized PPI of startle responses. Neither bumetanide nor RU28318 altered the effect of sevoflurane on synaptic activity.

CONCLUSIONS

Sevoflurane-enhanced neuronal excitation and elevated corticosteroid levels at the time of anesthesia contribute to the mechanisms initiating neonatal sevoflurane-induced long-term endocrine and neurobehavioral abnormalities.

Authors+Show Affiliations

Department of Anesthesiology, University of Florida College of Medicine, Gainesville, FL, USA.Department of Anesthesiology, University of Florida College of Medicine, Gainesville, FL, USA.Department of Anesthesiology, University of Florida College of Medicine, Gainesville, FL, USA; Department of Anesthesiology, People's Hospital of Zhengzhou University, Zhengzhou, P.R.China.Department of Anesthesiology, University of Florida College of Medicine, Gainesville, FL, USA.Department of Anesthesiology, University of Florida College of Medicine, Gainesville, FL, USA; The McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, USA.The McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, USA; Department of Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville, FL, USA.Department of Anesthesiology, University of Florida College of Medicine, Gainesville, FL, USA.Department of Anesthesiology, University of Florida College of Medicine, Gainesville, FL, USA; The McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, USA. Electronic address: amartynyuk@anest.ufl.edu.

Pub Type(s)

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

Language

eng

PubMed ID

26150359

Citation

Xu, Changqing, et al. "Anesthesia With Sevoflurane in Neonatal Rats: Developmental Neuroendocrine Abnormalities and Alleviating Effects of the Corticosteroid and Cl(-) Importer Antagonists." Psychoneuroendocrinology, vol. 60, 2015, pp. 173-81.
Xu C, Tan S, Zhang J, et al. Anesthesia with sevoflurane in neonatal rats: Developmental neuroendocrine abnormalities and alleviating effects of the corticosteroid and Cl(-) importer antagonists. Psychoneuroendocrinology. 2015;60:173-81.
Xu, C., Tan, S., Zhang, J., Seubert, C. N., Gravenstein, N., Sumners, C., Vasilopoulos, T., & Martynyuk, A. E. (2015). Anesthesia with sevoflurane in neonatal rats: Developmental neuroendocrine abnormalities and alleviating effects of the corticosteroid and Cl(-) importer antagonists. Psychoneuroendocrinology, 60, 173-81. https://doi.org/10.1016/j.psyneuen.2015.06.016
Xu C, et al. Anesthesia With Sevoflurane in Neonatal Rats: Developmental Neuroendocrine Abnormalities and Alleviating Effects of the Corticosteroid and Cl(-) Importer Antagonists. Psychoneuroendocrinology. 2015;60:173-81. PubMed PMID: 26150359.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anesthesia with sevoflurane in neonatal rats: Developmental neuroendocrine abnormalities and alleviating effects of the corticosteroid and Cl(-) importer antagonists. AU - Xu,Changqing, AU - Tan,Sijie, AU - Zhang,Jiaqiang, AU - Seubert,Christoph N, AU - Gravenstein,Nikolaus, AU - Sumners,Colin, AU - Vasilopoulos,Terrie, AU - Martynyuk,Anatoly E, Y1 - 2015/06/25/ PY - 2015/02/17/received PY - 2015/05/22/revised PY - 2015/06/22/accepted PY - 2015/7/8/entrez PY - 2015/7/8/pubmed PY - 2016/5/3/medline KW - Brain KW - Corticosterone KW - Endocrine KW - GABA KW - Neonatal KW - Sevoflurane SP - 173 EP - 81 JF - Psychoneuroendocrinology JO - Psychoneuroendocrinology VL - 60 N2 - BACKGROUND: 1.5 million children under 12 months of age are exposed to general anesthesia annually in the United States alone. Human and especially animal studies provide evidence that exposure to general anesthesia during the early postnatal period may lead to long-term neurocognitive abnormalities via poorly understood mechanisms. We investigated whether an immature stress response system and γ-aminobutyric acid (GABA) type A receptor activities are involved in mediating these abnormalities. METHODS: Sprague-Dawley rats at postnatal days 4, 5 or 6 were anesthetized with 2.1% sevoflurane for 6h; maternally separated and house reared rats served as controls. RESULTS: Sevoflurane anesthesia markedly increased corticosterone levels in rat pups of both genders. In adulthood, these rats responded to stress with heightened secretion of corticosterone and a greater increase in corticosterone levels in males versus females. Only male rats, previously exposed to neonatal sevoflurane, had a higher frequency of miniature inhibitory postsynaptic currents in CA1 neurons, spent a shorter time in open arms of the elevated plus maze (EPM) and exhibited impaired prepulse inhibition (PPI) of startle. Pretreatment of male rats prior to sevoflurane with the Na(+)-K(+)-2Cl(-) cotransporter inhibitor, bumetanide, or the mineralocorticoid receptor antagonist, RU28318, normalized endocrine responses to stress and the EPM behavior in adulthood, while only those pretreated with bumetanide exhibited normalized PPI of startle responses. Neither bumetanide nor RU28318 altered the effect of sevoflurane on synaptic activity. CONCLUSIONS: Sevoflurane-enhanced neuronal excitation and elevated corticosteroid levels at the time of anesthesia contribute to the mechanisms initiating neonatal sevoflurane-induced long-term endocrine and neurobehavioral abnormalities. SN - 1873-3360 UR - https://www.unboundmedicine.com/medline/citation/26150359/Anesthesia_with_sevoflurane_in_neonatal_rats:_Developmental_neuroendocrine_abnormalities_and_alleviating_effects_of_the_corticosteroid_and_Cl____importer_antagonists_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4530(15)00231-0 DB - PRIME DP - Unbound Medicine ER -