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Heightened stress response and cognitive impairment after repeated neonatal sevoflurane exposures might be linked to excessive GABAAR-mediated depolarization.
J Anesth. 2016 10; 30(5):834-41.JA

Abstract

OBJECTIVE

Children with repeated exposures to anesthesia at an early age are at an increased risk of cognitive impairment. Data in the literature link increased developmental depolarizing γ-aminobutyric acid (GABA) type A receptor (GABAAR) at younger age to neurodevelopmental disorders. Here we investigated the involvement of GABAergic signaling during development in mediating the adverse effects of repeated sevoflurane exposures.

METHODS

Sprague-Dawley male rats received repeated exposures to 3 % sevoflurane for 2 h daily for 3 consecutive days on postnatal days (P) 4, 5, and 6; maternally separated and unseparated rats served as controls. A subgroup of rats received three injections of the Na(+)-K(+)-2Cl(-) cotransporter inhibitor, bumetanide (1.82 mg/kg, intraperitoneally) 15 min prior to initiation of each sevoflurane exposure.

RESULTS

The results showed that repeated neonatal sevoflurane exposures contribute to learning and memory impairment in the Morris water maze (MWM) at P60. The corticosterone level was significantly increased immediately after repeated neonatal sevoflurane exposures. Repeated neonatal sevoflurane exposures heightened the secretion of corticosterone in response to stress in P7 and P60 rats. Pretreatment of male rats prior to each sevoflurane exposure with bumetanide attenuated the corticosterone level immediately after repeated neonatal sevoflurane exposures, normalized endocrine response to stress at P7 and P60, and attenuated the sevoflurane-induced learning and memory impairment in the MWM.

CONCLUSION

These data suggested that the heightened stress response and cognitive impairment after repeated neonatal sevoflurane exposures might be linked to excessive GABAAR-mediated depolarization.

Authors+Show Affiliations

Department of Anesthesiology, The First People's Hospital of Yancheng, Yancheng, 224005, Jiangsu, People's Republic of China.Department of Anesthesiology, The First People's Hospital of Yancheng, Yancheng, 224005, Jiangsu, People's Republic of China.Department of Anesthesiology, The First People's Hospital of Yancheng, Yancheng, 224005, Jiangsu, People's Republic of China.Department of Anesthesiology, The First People's Hospital of Yancheng, Yancheng, 224005, Jiangsu, People's Republic of China.Department of Anesthesiology, The First People's Hospital of Yancheng, Yancheng, 224005, Jiangsu, People's Republic of China.Department of Anesthesiology, The First People's Hospital of Yancheng, Yancheng, 224005, Jiangsu, People's Republic of China. ddxh2012@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27435414

Citation

Liu, Guanghai, et al. "Heightened Stress Response and Cognitive Impairment After Repeated Neonatal Sevoflurane Exposures Might Be Linked to Excessive GABAAR-mediated Depolarization." Journal of Anesthesia, vol. 30, no. 5, 2016, pp. 834-41.
Liu G, Zhu T, Zhang A, et al. Heightened stress response and cognitive impairment after repeated neonatal sevoflurane exposures might be linked to excessive GABAAR-mediated depolarization. J Anesth. 2016;30(5):834-41.
Liu, G., Zhu, T., Zhang, A., Li, F., Qian, W., & Qian, B. (2016). Heightened stress response and cognitive impairment after repeated neonatal sevoflurane exposures might be linked to excessive GABAAR-mediated depolarization. Journal of Anesthesia, 30(5), 834-41. https://doi.org/10.1007/s00540-016-2215-0
Liu G, et al. Heightened Stress Response and Cognitive Impairment After Repeated Neonatal Sevoflurane Exposures Might Be Linked to Excessive GABAAR-mediated Depolarization. J Anesth. 2016;30(5):834-41. PubMed PMID: 27435414.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Heightened stress response and cognitive impairment after repeated neonatal sevoflurane exposures might be linked to excessive GABAAR-mediated depolarization. AU - Liu,Guanghai, AU - Zhu,Tiangui, AU - Zhang,Aihua, AU - Li,Feng, AU - Qian,Weidong, AU - Qian,Bin, Y1 - 2016/07/19/ PY - 2016/03/15/received PY - 2016/07/05/accepted PY - 2016/7/21/entrez PY - 2016/7/21/pubmed PY - 2017/8/10/medline KW - Bumetanide KW - Corticosterone KW - Endocrine response KW - Repeated neonatal sevoflurane exposures KW - γ-Aminobutyric acid type A receptor SP - 834 EP - 41 JF - Journal of anesthesia JO - J Anesth VL - 30 IS - 5 N2 - OBJECTIVE: Children with repeated exposures to anesthesia at an early age are at an increased risk of cognitive impairment. Data in the literature link increased developmental depolarizing γ-aminobutyric acid (GABA) type A receptor (GABAAR) at younger age to neurodevelopmental disorders. Here we investigated the involvement of GABAergic signaling during development in mediating the adverse effects of repeated sevoflurane exposures. METHODS: Sprague-Dawley male rats received repeated exposures to 3 % sevoflurane for 2 h daily for 3 consecutive days on postnatal days (P) 4, 5, and 6; maternally separated and unseparated rats served as controls. A subgroup of rats received three injections of the Na(+)-K(+)-2Cl(-) cotransporter inhibitor, bumetanide (1.82 mg/kg, intraperitoneally) 15 min prior to initiation of each sevoflurane exposure. RESULTS: The results showed that repeated neonatal sevoflurane exposures contribute to learning and memory impairment in the Morris water maze (MWM) at P60. The corticosterone level was significantly increased immediately after repeated neonatal sevoflurane exposures. Repeated neonatal sevoflurane exposures heightened the secretion of corticosterone in response to stress in P7 and P60 rats. Pretreatment of male rats prior to each sevoflurane exposure with bumetanide attenuated the corticosterone level immediately after repeated neonatal sevoflurane exposures, normalized endocrine response to stress at P7 and P60, and attenuated the sevoflurane-induced learning and memory impairment in the MWM. CONCLUSION: These data suggested that the heightened stress response and cognitive impairment after repeated neonatal sevoflurane exposures might be linked to excessive GABAAR-mediated depolarization. SN - 1438-8359 UR - https://www.unboundmedicine.com/medline/citation/27435414/Heightened_stress_response_and_cognitive_impairment_after_repeated_neonatal_sevoflurane_exposures_might_be_linked_to_excessive_GABAAR_mediated_depolarization_ L2 - https://dx.doi.org/10.1007/s00540-016-2215-0 DB - PRIME DP - Unbound Medicine ER -