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Dexmedetomidine attenuates repeated propofol exposure-induced hippocampal apoptosis, PI3K/Akt/Gsk-3β signaling disruption, and juvenile cognitive deficits in neonatal rats.
Mol Med Rep. 2016 Jul; 14(1):769-75.MM

Abstract

Propofol is one of the most widely used intravenous anesthetics. However, repeated exposure to propofol may cause neurodegeneration in the developing brain. Dexmedetomidine (Dex), an α2 adrenoceptor agonist, has been previously demonstrated to provide neuroprotection against neuroapoptosis and neurocognitive impairments induced by several anesthetics. Thus, the current study aimed to investigate the effect of Dex on neonatal propofol-induced neuroapoptosis and juvenile spatial learning/memory deficits. Propofol (30 mg/kg) was intraperiotoneally administered to 7‑day‑old Sprague Dawley rats (n=75) three times each day at 90 min intervals for seven consecutive days with or without Dex (75 µg/kg) treatment 20 min prior to propofol injection. Following repeated propofol exposure, reduced Akt and GSK‑3β phosphorylation, increased cleaved caspase‑3 expression levels, an increased Bax/Bcl‑2 ratio, and increased terminal deoxynucleotidyl transferase‑mediated dUTP nick‑end labeling (TUNEL)‑positive cells in the CA1 hippocampal subregion were observed. Morris Water Maze testing at postnatal day 29 also demonstrated spatial learning and memory deficits following propofol treatment compared with the control group. Notably, these changes were significantly attenuated by Dex pretreatment. The results of the current study demonstrated that Dex ameliorates the neurocognitive impairment induced by repeated neonatal propofol challenge in rats, partially via its anti‑apoptotic action and normalization of the disruption to the PI3K/Akt/GSK‑3β signaling pathway. The present study provides preliminary evidence demonstrating the safety of propofol on the neonatal brain and the potential use of dexmedetomidine pretreatment in pediatric patients.

Authors+Show Affiliations

Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, P.R. China.Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, P.R. China.Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, P.R. China.Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, P.R. China.Department of Otolaryngology, 316 Hospital of People's Liberation Army, Beijing 100093, P.R. China.Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, P.R. China.Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, P.R. China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27222147

Citation

Wang, Yujie, et al. "Dexmedetomidine Attenuates Repeated Propofol Exposure-induced Hippocampal Apoptosis, PI3K/Akt/Gsk-3β Signaling Disruption, and Juvenile Cognitive Deficits in Neonatal Rats." Molecular Medicine Reports, vol. 14, no. 1, 2016, pp. 769-75.
Wang Y, Wu C, Han B, et al. Dexmedetomidine attenuates repeated propofol exposure-induced hippocampal apoptosis, PI3K/Akt/Gsk-3β signaling disruption, and juvenile cognitive deficits in neonatal rats. Mol Med Rep. 2016;14(1):769-75.
Wang, Y., Wu, C., Han, B., Xu, F., Mao, M., Guo, X., & Wang, J. (2016). Dexmedetomidine attenuates repeated propofol exposure-induced hippocampal apoptosis, PI3K/Akt/Gsk-3β signaling disruption, and juvenile cognitive deficits in neonatal rats. Molecular Medicine Reports, 14(1), 769-75. https://doi.org/10.3892/mmr.2016.5321
Wang Y, et al. Dexmedetomidine Attenuates Repeated Propofol Exposure-induced Hippocampal Apoptosis, PI3K/Akt/Gsk-3β Signaling Disruption, and Juvenile Cognitive Deficits in Neonatal Rats. Mol Med Rep. 2016;14(1):769-75. PubMed PMID: 27222147.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dexmedetomidine attenuates repeated propofol exposure-induced hippocampal apoptosis, PI3K/Akt/Gsk-3β signaling disruption, and juvenile cognitive deficits in neonatal rats. AU - Wang,Yujie, AU - Wu,Changyi, AU - Han,Bin, AU - Xu,Fei, AU - Mao,Mingfeng, AU - Guo,Xiangyang, AU - Wang,Jun, Y1 - 2016/05/23/ PY - 2015/06/27/received PY - 2016/05/03/accepted PY - 2016/5/26/entrez PY - 2016/5/26/pubmed PY - 2017/4/7/medline SP - 769 EP - 75 JF - Molecular medicine reports JO - Mol Med Rep VL - 14 IS - 1 N2 - Propofol is one of the most widely used intravenous anesthetics. However, repeated exposure to propofol may cause neurodegeneration in the developing brain. Dexmedetomidine (Dex), an α2 adrenoceptor agonist, has been previously demonstrated to provide neuroprotection against neuroapoptosis and neurocognitive impairments induced by several anesthetics. Thus, the current study aimed to investigate the effect of Dex on neonatal propofol-induced neuroapoptosis and juvenile spatial learning/memory deficits. Propofol (30 mg/kg) was intraperiotoneally administered to 7‑day‑old Sprague Dawley rats (n=75) three times each day at 90 min intervals for seven consecutive days with or without Dex (75 µg/kg) treatment 20 min prior to propofol injection. Following repeated propofol exposure, reduced Akt and GSK‑3β phosphorylation, increased cleaved caspase‑3 expression levels, an increased Bax/Bcl‑2 ratio, and increased terminal deoxynucleotidyl transferase‑mediated dUTP nick‑end labeling (TUNEL)‑positive cells in the CA1 hippocampal subregion were observed. Morris Water Maze testing at postnatal day 29 also demonstrated spatial learning and memory deficits following propofol treatment compared with the control group. Notably, these changes were significantly attenuated by Dex pretreatment. The results of the current study demonstrated that Dex ameliorates the neurocognitive impairment induced by repeated neonatal propofol challenge in rats, partially via its anti‑apoptotic action and normalization of the disruption to the PI3K/Akt/GSK‑3β signaling pathway. The present study provides preliminary evidence demonstrating the safety of propofol on the neonatal brain and the potential use of dexmedetomidine pretreatment in pediatric patients. SN - 1791-3004 UR - https://www.unboundmedicine.com/medline/citation/27222147/Dexmedetomidine_attenuates_repeated_propofol_exposure_induced_hippocampal_apoptosis_PI3K/Akt/Gsk_3β_signaling_disruption_and_juvenile_cognitive_deficits_in_neonatal_rats_ L2 - http://www.spandidos-publications.com/mmr/14/1/769 DB - PRIME DP - Unbound Medicine ER -