The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Zhongcong Xie - One of the best experts on this subject based on the ideXlab platform.
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dexmedetomidine and clonidine attenuate Sevoflurane induced tau phosphorylation and cognitive impairment in young mice via α 2 adrenergic receptor
Anesthesia & Analgesia, 2020Co-Authors: Mingyang Sun, Yuanlin Dong, Sulpicio G Soriano, Yiying Zhang, Feng Liang, Jiaqiang Zhang, Zhongcong XieAbstract:BACKGROUND Anesthetic Sevoflurane induces tau phosphorylation and cognitive impairment in young mice. The underlying mechanism and the targeted interventions remain largely unexplored. We hypothesized that dexmedetomidine and clonidine attenuated Sevoflurane-induced tau phosphorylation and cognitive impairment by acting on α-2 adrenergic receptor. METHODS Six-day-old mice received anesthesia with 3% Sevoflurane 2 hours daily on postnatal days 6, 9, and 12. Alpha-2 adrenergic receptor agonist dexmedetomidine and clonidine were used to treat the mice with and without the α-2 adrenergic receptor antagonist yohimbine. Mouse hippocampi were harvested and subjected to western blot analysis. The New Object Recognition Test and Morris Water Maze were used to measure cognitive function. We analyzed the primary outcomes by using 2- and 1-way analysis of variance (ANOVA) and Mann-Whitney U test to determine the effects of Sevoflurane on the amounts of phosphorylated tau, postsynaptic density-95, and cognitive function in young mice after the treatments with dexmedetomidine, clonidine, and yohimbine. RESULTS Both dexmedetomidine and clonidine attenuated the Sevoflurane-induced increase in phosphorylated tau amount (94 ± 16.3% [dexmedetomidine plus Sevoflurane] versus 240 ± 67.8% [vehicle plus Sevoflurane], P < .001; 125 ± 13.5% [clonidine plus Sevoflurane] versus 355 ± 57.6% [vehicle plus Sevoflurane], P < .001; mean ± standard deviation), Sevoflurane-induced reduction in postsynaptic density-95 (82 ± 6.6% [dexmedetomidine plus Sevoflurane] versus 31 ± 12.4% [vehicle plus Sevoflurane], P < .001; 95 ± 6.4% [clonidine plus Sevoflurane] versus 62 ± 18.4% [vehicle plus Sevoflurane], P < .001), and cognitive impairment in the young mice. Interestingly, yohimbine reversed the effects of dexmedetomidine and clonidine on attenuating the Sevoflurane-induced changes in phosphorylated tau, postsynaptic density-95, and cognitive function. CONCLUSIONS Dexmedetomidine and clonidine could inhibit the Sevoflurane-induced tau phosphorylation and cognitive impairment via activation of α-2 adrenergic receptor. More studies are needed to confirm the results and to determine the clinical relevance of these findings.
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Sevoflurane induces neuronal activation and behavioral hyperactivity in young mice
Scientific Reports, 2020Co-Authors: Yuanlin Dong, Yiying Zhang, Lei Yang, Hoai T Ton, Ruohe Zhao, Erez Geron, Guang Yang, Zhongcong XieAbstract:Sevoflurane, a commonly used anesthetic, may cause agitation in patients. However, the mechanism underlying this clinical observation remains largely unknown. We thus assessed the effects of Sevoflurane on neuronal activation and behaviors in mice. Ten-day-old mice received 2% Sevoflurane, 1% isoflurane, or 6% desflurane for 10 minutes. The behavioral activities were recorded and evaluated at one minute after the loss of righting reflex in the mice, which was about two minutes after the anesthetic administration. The neuronal activation was evaluated by c-Fos expression and calcium imaging at one minute after the anesthetic administration. Propofol, which reduces neuronal activation, was used to determine the cause-and-effect of Sevoflurane. We found that Sevoflurane caused an increase in neuronal activation in primary somatosensory cortex of young mice and behavioral hyperactivity in the mice at one minute after the loss of righting reflex. Desflurane did not induce behavioral hyperactivity and isoflurane only caused behavioral hyperactivity with borderline significance. Finally, propofol attenuated the Sevoflurane-induced increase in neuronal activation and behavioral hyperactivity in young mice. These results demonstrate an unexpected Sevoflurane-induced increase in neuronal activation and behavioral hyperactivity in young mice. These findings suggest the potential mechanisms underlying the Sevoflurane-induced agitation and will promote future studies to further determine whether anesthetics can induce behavioral hyperactivity via increasing neuronal activation.
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cyclophilin d contributes to anesthesia neurotoxicity in the developing brain
Frontiers in Cell and Developmental Biology, 2020Co-Authors: Yuanlin Dong, Yiying Zhang, Feng Liang, Ning Liufu, Jialin C Zheng, Zhongcong XieAbstract:Anesthetic Sevoflurane induces mitochondrial dysfunction, impairment of neurogenesis, and cognitive impairment in young mice, but the underlying mechanism remains to be determined. Cyclophilin D (CypD) is a modulatory factor for the mitochondrial permeability transition pore (mPTP). We, therefore, set out to evaluate the role of CypD in these Sevoflurane-induced changes in vitro and in young mice. Wild-type (WT) and CypD knockout (KO) young (postnatal day 6, 7, and 8) mice received 3% Sevoflurane 2 h daily and the neural progenitor cells (NPCs) harvested from the WT or CypD KO mice received 4.1% Sevoflurane. We used immunohistochemistry and immunocytochemistry imaging, flow cytometry, Western blot, RT-PCR, co-immunoprecipitation, and Morris Water Maze to assess the interaction of Sevoflurane and CypD on mitochondria function, neurogenesis, and cognition in vitro and in WT or CypD KO mice. We demonstrated that the Sevoflurane anesthesia induced accumulation of CypD, mitochondrial dysfunction, impairment of neurogenesis, and cognitive impairment in WT mice or NPCs harvested from WT mice, but not in CypD KO mice or NPCs harvested from CypD KO mice. Furthermore, the Sevoflurane anesthesia reduced the binding of CypD with Adenine nucleotide translocator, the other component of mPTP. These data suggest that the Sevoflurane anesthesia might induce a CypD-dependent mitochondria dysfunction, impairment of neurogenesis, and cognitive impairment in young mice and NPCs.
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anesthetic Sevoflurane reduces levels of hippocalcin and postsynaptic density protein 95
Molecular Neurobiology, 2015Co-Authors: Yuanlin Dong, Yiying Zhang, Jie Zhang, Chen Zhou, Zhongcong XieAbstract:Sevoflurane, the commonly used inhalation anesthetic in children, has been shown to enhance cytosolic calcium levels and induce cognitive impairment in young mice. However, the downstream consequences of the Sevoflurane-induced elevation in cytosolic calcium levels and the upstream mechanisms of the Sevoflurane-induced cognitive impairment remain largely to be determined. Hippocalcin is one of the neuronal calcium sensor proteins, and also binds to postsynaptic density protein 95 (PSD-95). We therefore set out to determine the effects of Sevoflurane on the levels of hippocalcin and PSD-95 in vitro and in vivo. Hippocampus neurons from mice and 6-day-old mice were treated with 4.1 % Sevoflurane for 6 h or 3 % Sevoflurane 2 h daily for 3 days, respectively. We then measured the levels of hippocalcin and PSD-95, and assessed whether BAPTA, an intracellular calcium chelator, and memantine, a partial antagonist of the NMDA receptor, could inhibit the Sevoflurane’s effects. We found that Sevoflurane decreased the levels of hippocalcin and PSD-95 in the neurons; and decreased the levels of hippocalcin and PSD-95 in the hippocampus of mice immediately after the anesthesia, but only the PSD-95 levels three weeks after the anesthesia. BAPTA inhibited the Sevoflurane’s effects in the neurons. Memantine attenuated the Sevoflurane-induced reductions in the levels of hippocalcin and PSD-95, as well as the Sevoflurane-induced cognitive impairment in mice. These data suggested that Sevoflurane decreased the levels of hippocalcin and PSD-95, which could serve as one of bridge mechanisms between the Sevoflurane-induced elevation of cytosolic calcium levels and the Sevoflurane-induced cognitive impairment.
Shigeho Morita - One of the best experts on this subject based on the ideXlab platform.
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emergence agitation after Sevoflurane versus propofol in pediatric patients
Anesthesia & Analgesia, 2000Co-Authors: Shoichi Uezono, Yoshinori Nakata, Takahisa Goto, Katsuo Terui, Fumito Ichinose, Yoshiki Ishguro, Shigeho MoritaAbstract:Sevoflurane may be associated with a high incidence of emergence agitation in preschool children. We tested the hypothesis that maintenance of anesthesia with propofol after Sevoflurane induction would reduce the incidence of this excitatory behavior compared with continuing Sevoflurane for maintena
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effects of xenon on hemodynamic responses to skin incision in humans
Anesthesiology, 1999Co-Authors: Yoshinori Nakata, Takahisa Goto, Shigeho MoritaAbstract:BACKGROUND The authors evaluated the hemodynamic suppressive effects of xenon in combination with Sevoflurane at skin incision in patients undergoing surgery. METHODS Forty patients were assigned randomly to receive one of the following four anesthetics: 1.3 minimum alveolar concentration (MAC) Sevoflurane, 0.7 MAC xenon with 0.6 MAC Sevoflurane, 1 MAC xenon with 0.3 MAC Sevoflurane, or 0.7 MAC nitrous oxide with 0.6 MAC Sevoflurane (n = 10 each group). Systolic blood pressure and heart rate were measured before anesthesia, before incision, and approximately 1 min after incision. RESULTS The changes in hemodynamic variables in response to incision were less with Sevoflurane in combination with xenon and nitrous oxide than with Sevoflurane alone. Changes in heart rate (in beats/min) were 19+/-11 (+/- SD) for Sevoflurane alone, 11+/-6 for 0.7 MAC xenon-Sevoflurane, 4+/-4 for 1 MAC xenon-Sevoflurane, and 8+/-7 for nitrous oxide-Sevoflurane. Changes in systolic blood pressure were 35+/-18 mmHg for Sevoflurane alone, 18+/-8 mmHg for 0.7 MAC xenon-Sevoflurane, 16+/-7 mmHg for 1 MAC xenon-Sevoflurane, and 14+/-10 mmHg for nitrous oxide-Sevoflurane. CONCLUSIONS Xenon and nitrous oxide in combination with Sevoflurane can reduce hemodynamic responses to skin incision compared with Sevoflurane alone. One probable explanation may be that xenon has analgesic properties similar to those of nitrous oxide, although the exact mechanism is yet to be determined.
Ian Smith - One of the best experts on this subject based on the ideXlab platform.
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inhalation induction with Sevoflurane a double blind comparison with propofol
BJA: British Journal of Anaesthesia, 1997Co-Authors: A J Thwaites, S Edmends, Ian SmithAbstract:We conducted a randomized, double-blind comparison of 8% Sevoflurane and propofol as induction agents for day-case cystoscopy in 102 patients. All patients received an i.v. cannula and breathed oxygen 5 litre min-1. Anaesthesia was induced with propofol i.v. or inhalation of 8% Sevoflurane and 10% Intralipid (as a placebo) i.v., delivered by a blinded observer. Anaesthesia was maintained in all patients with 2% Sevoflurane via a face mask. Induction of anaesthesia with Sevoflurane was significantly slower compared with propofol (mean 84 (SD 24) s vs 57 (11) s), but was associated with a lower incidence of apnoea (16% vs 65%) and a shorter time to establish spontaneous ventilation (94 (34) s vs 126 (79) s). Induction complications were uncommon in each group but the transition to maintenance was smoother with Sevoflurane and was associated with less hypotension compared with propofol. Emergence from anaesthesia induced with Sevoflurane occurred significantly earlier compared with propofol (5.2 (2.2) min vs 7.0 (3.2) min) and anaesthetic induction was also significantly cheaper with Sevoflurane. According to a postoperative questionnaire, the majority of patients found both anaesthetic techniques acceptable. Nevertheless, significnatly more patients (14%) rated induction with Sevoflurane as unpleasant compared with propofol (0) and significantly more patients (24%) would not choose Sevoflurane induction compared with propofol (6%). This phenomenon may have been related to the particular patient population studied, however. Inhalation induction with 8% Sevoflurane would appear to offer several objective advantages compared with induction with propofol in day-case patients, although a significant minority may dislike this technique.
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comparison of induction maintenance and recovery characteristics of Sevoflurane n2o and propofol Sevoflurane n2o with propofol isoflurane n2o anesthesia
Anesthesia & Analgesia, 1992Co-Authors: Ian Smith, Yifeng Ding, Paul F. WhiteAbstract:Induction of, maintenance of, and recovery from Sevoflurane anesthesia were compared with propofol and isoflurane anesthesia when administered with nitrous oxide to patients undergoing gynecologic surgery. Seventy-five healthy (ASA I or II), consenting patients were randomly assigned to receive either (I) propofol for induction of anesthesia and isoflurane-nitrous oxide for maintenance (control), (II) propofol for induction and Sevoflurane-nitrous oxide for maintenance, or (III) Sevoflurane-nitrous oxide for induction and maintenance of anesthesia. Inhaled induction of anesthesia with Sevoflurane-nitrous oxide was rapid (109 +/- 25 s to loss of consciousness) and without any untoward hemodynamic changes or episodes of coughing and laryngospasm. Mean arterial blood pressure after induction of anesthesia with propofol (71 +/- 11, 73 +/- 12 mm Hg for groups I and II, respectively) was lower than when Sevoflurane (80 +/- 14 mm Hg) was used. The emergence time after discontinuation of isoflurane-nitrous oxide (6.7 +/- 2.2 min) was significantly longer than after propofol-Sevoflurane-nitrous oxide or Sevoflurane-nitrous oxide alone (4.1 +/- 2.2 and 4.0 +/- 2.0 min for groups II and III, respectively). However, later recovery events did not differ between groups. Serum fluoride levels increased after administration of Sevoflurane but not isoflurane. The levels of fluoride ions correlated with the degree of exposure to Sevoflurane in MAC-hours. In conclusion, induction of anesthesia with either propofol or Sevoflurane-nitrous oxide was rapid and without significant side effects. Emergence and early recovery after maintenance of anesthesia with Sevoflurane-nitrous oxide was significantly faster than that after an isoflurane-nitrous oxide combination.
Yiying Zhang - One of the best experts on this subject based on the ideXlab platform.
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dexmedetomidine and clonidine attenuate Sevoflurane induced tau phosphorylation and cognitive impairment in young mice via α 2 adrenergic receptor
Anesthesia & Analgesia, 2020Co-Authors: Mingyang Sun, Yuanlin Dong, Sulpicio G Soriano, Yiying Zhang, Feng Liang, Jiaqiang Zhang, Zhongcong XieAbstract:BACKGROUND Anesthetic Sevoflurane induces tau phosphorylation and cognitive impairment in young mice. The underlying mechanism and the targeted interventions remain largely unexplored. We hypothesized that dexmedetomidine and clonidine attenuated Sevoflurane-induced tau phosphorylation and cognitive impairment by acting on α-2 adrenergic receptor. METHODS Six-day-old mice received anesthesia with 3% Sevoflurane 2 hours daily on postnatal days 6, 9, and 12. Alpha-2 adrenergic receptor agonist dexmedetomidine and clonidine were used to treat the mice with and without the α-2 adrenergic receptor antagonist yohimbine. Mouse hippocampi were harvested and subjected to western blot analysis. The New Object Recognition Test and Morris Water Maze were used to measure cognitive function. We analyzed the primary outcomes by using 2- and 1-way analysis of variance (ANOVA) and Mann-Whitney U test to determine the effects of Sevoflurane on the amounts of phosphorylated tau, postsynaptic density-95, and cognitive function in young mice after the treatments with dexmedetomidine, clonidine, and yohimbine. RESULTS Both dexmedetomidine and clonidine attenuated the Sevoflurane-induced increase in phosphorylated tau amount (94 ± 16.3% [dexmedetomidine plus Sevoflurane] versus 240 ± 67.8% [vehicle plus Sevoflurane], P < .001; 125 ± 13.5% [clonidine plus Sevoflurane] versus 355 ± 57.6% [vehicle plus Sevoflurane], P < .001; mean ± standard deviation), Sevoflurane-induced reduction in postsynaptic density-95 (82 ± 6.6% [dexmedetomidine plus Sevoflurane] versus 31 ± 12.4% [vehicle plus Sevoflurane], P < .001; 95 ± 6.4% [clonidine plus Sevoflurane] versus 62 ± 18.4% [vehicle plus Sevoflurane], P < .001), and cognitive impairment in the young mice. Interestingly, yohimbine reversed the effects of dexmedetomidine and clonidine on attenuating the Sevoflurane-induced changes in phosphorylated tau, postsynaptic density-95, and cognitive function. CONCLUSIONS Dexmedetomidine and clonidine could inhibit the Sevoflurane-induced tau phosphorylation and cognitive impairment via activation of α-2 adrenergic receptor. More studies are needed to confirm the results and to determine the clinical relevance of these findings.
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Sevoflurane induces neuronal activation and behavioral hyperactivity in young mice
Scientific Reports, 2020Co-Authors: Yuanlin Dong, Yiying Zhang, Lei Yang, Hoai T Ton, Ruohe Zhao, Erez Geron, Guang Yang, Zhongcong XieAbstract:Sevoflurane, a commonly used anesthetic, may cause agitation in patients. However, the mechanism underlying this clinical observation remains largely unknown. We thus assessed the effects of Sevoflurane on neuronal activation and behaviors in mice. Ten-day-old mice received 2% Sevoflurane, 1% isoflurane, or 6% desflurane for 10 minutes. The behavioral activities were recorded and evaluated at one minute after the loss of righting reflex in the mice, which was about two minutes after the anesthetic administration. The neuronal activation was evaluated by c-Fos expression and calcium imaging at one minute after the anesthetic administration. Propofol, which reduces neuronal activation, was used to determine the cause-and-effect of Sevoflurane. We found that Sevoflurane caused an increase in neuronal activation in primary somatosensory cortex of young mice and behavioral hyperactivity in the mice at one minute after the loss of righting reflex. Desflurane did not induce behavioral hyperactivity and isoflurane only caused behavioral hyperactivity with borderline significance. Finally, propofol attenuated the Sevoflurane-induced increase in neuronal activation and behavioral hyperactivity in young mice. These results demonstrate an unexpected Sevoflurane-induced increase in neuronal activation and behavioral hyperactivity in young mice. These findings suggest the potential mechanisms underlying the Sevoflurane-induced agitation and will promote future studies to further determine whether anesthetics can induce behavioral hyperactivity via increasing neuronal activation.
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cyclophilin d contributes to anesthesia neurotoxicity in the developing brain
Frontiers in Cell and Developmental Biology, 2020Co-Authors: Yuanlin Dong, Yiying Zhang, Feng Liang, Ning Liufu, Jialin C Zheng, Zhongcong XieAbstract:Anesthetic Sevoflurane induces mitochondrial dysfunction, impairment of neurogenesis, and cognitive impairment in young mice, but the underlying mechanism remains to be determined. Cyclophilin D (CypD) is a modulatory factor for the mitochondrial permeability transition pore (mPTP). We, therefore, set out to evaluate the role of CypD in these Sevoflurane-induced changes in vitro and in young mice. Wild-type (WT) and CypD knockout (KO) young (postnatal day 6, 7, and 8) mice received 3% Sevoflurane 2 h daily and the neural progenitor cells (NPCs) harvested from the WT or CypD KO mice received 4.1% Sevoflurane. We used immunohistochemistry and immunocytochemistry imaging, flow cytometry, Western blot, RT-PCR, co-immunoprecipitation, and Morris Water Maze to assess the interaction of Sevoflurane and CypD on mitochondria function, neurogenesis, and cognition in vitro and in WT or CypD KO mice. We demonstrated that the Sevoflurane anesthesia induced accumulation of CypD, mitochondrial dysfunction, impairment of neurogenesis, and cognitive impairment in WT mice or NPCs harvested from WT mice, but not in CypD KO mice or NPCs harvested from CypD KO mice. Furthermore, the Sevoflurane anesthesia reduced the binding of CypD with Adenine nucleotide translocator, the other component of mPTP. These data suggest that the Sevoflurane anesthesia might induce a CypD-dependent mitochondria dysfunction, impairment of neurogenesis, and cognitive impairment in young mice and NPCs.
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anesthetic Sevoflurane reduces levels of hippocalcin and postsynaptic density protein 95
Molecular Neurobiology, 2015Co-Authors: Yuanlin Dong, Yiying Zhang, Jie Zhang, Chen Zhou, Zhongcong XieAbstract:Sevoflurane, the commonly used inhalation anesthetic in children, has been shown to enhance cytosolic calcium levels and induce cognitive impairment in young mice. However, the downstream consequences of the Sevoflurane-induced elevation in cytosolic calcium levels and the upstream mechanisms of the Sevoflurane-induced cognitive impairment remain largely to be determined. Hippocalcin is one of the neuronal calcium sensor proteins, and also binds to postsynaptic density protein 95 (PSD-95). We therefore set out to determine the effects of Sevoflurane on the levels of hippocalcin and PSD-95 in vitro and in vivo. Hippocampus neurons from mice and 6-day-old mice were treated with 4.1 % Sevoflurane for 6 h or 3 % Sevoflurane 2 h daily for 3 days, respectively. We then measured the levels of hippocalcin and PSD-95, and assessed whether BAPTA, an intracellular calcium chelator, and memantine, a partial antagonist of the NMDA receptor, could inhibit the Sevoflurane’s effects. We found that Sevoflurane decreased the levels of hippocalcin and PSD-95 in the neurons; and decreased the levels of hippocalcin and PSD-95 in the hippocampus of mice immediately after the anesthesia, but only the PSD-95 levels three weeks after the anesthesia. BAPTA inhibited the Sevoflurane’s effects in the neurons. Memantine attenuated the Sevoflurane-induced reductions in the levels of hippocalcin and PSD-95, as well as the Sevoflurane-induced cognitive impairment in mice. These data suggested that Sevoflurane decreased the levels of hippocalcin and PSD-95, which could serve as one of bridge mechanisms between the Sevoflurane-induced elevation of cytosolic calcium levels and the Sevoflurane-induced cognitive impairment.
Yuanlin Dong - One of the best experts on this subject based on the ideXlab platform.
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dexmedetomidine and clonidine attenuate Sevoflurane induced tau phosphorylation and cognitive impairment in young mice via α 2 adrenergic receptor
Anesthesia & Analgesia, 2020Co-Authors: Mingyang Sun, Yuanlin Dong, Sulpicio G Soriano, Yiying Zhang, Feng Liang, Jiaqiang Zhang, Zhongcong XieAbstract:BACKGROUND Anesthetic Sevoflurane induces tau phosphorylation and cognitive impairment in young mice. The underlying mechanism and the targeted interventions remain largely unexplored. We hypothesized that dexmedetomidine and clonidine attenuated Sevoflurane-induced tau phosphorylation and cognitive impairment by acting on α-2 adrenergic receptor. METHODS Six-day-old mice received anesthesia with 3% Sevoflurane 2 hours daily on postnatal days 6, 9, and 12. Alpha-2 adrenergic receptor agonist dexmedetomidine and clonidine were used to treat the mice with and without the α-2 adrenergic receptor antagonist yohimbine. Mouse hippocampi were harvested and subjected to western blot analysis. The New Object Recognition Test and Morris Water Maze were used to measure cognitive function. We analyzed the primary outcomes by using 2- and 1-way analysis of variance (ANOVA) and Mann-Whitney U test to determine the effects of Sevoflurane on the amounts of phosphorylated tau, postsynaptic density-95, and cognitive function in young mice after the treatments with dexmedetomidine, clonidine, and yohimbine. RESULTS Both dexmedetomidine and clonidine attenuated the Sevoflurane-induced increase in phosphorylated tau amount (94 ± 16.3% [dexmedetomidine plus Sevoflurane] versus 240 ± 67.8% [vehicle plus Sevoflurane], P < .001; 125 ± 13.5% [clonidine plus Sevoflurane] versus 355 ± 57.6% [vehicle plus Sevoflurane], P < .001; mean ± standard deviation), Sevoflurane-induced reduction in postsynaptic density-95 (82 ± 6.6% [dexmedetomidine plus Sevoflurane] versus 31 ± 12.4% [vehicle plus Sevoflurane], P < .001; 95 ± 6.4% [clonidine plus Sevoflurane] versus 62 ± 18.4% [vehicle plus Sevoflurane], P < .001), and cognitive impairment in the young mice. Interestingly, yohimbine reversed the effects of dexmedetomidine and clonidine on attenuating the Sevoflurane-induced changes in phosphorylated tau, postsynaptic density-95, and cognitive function. CONCLUSIONS Dexmedetomidine and clonidine could inhibit the Sevoflurane-induced tau phosphorylation and cognitive impairment via activation of α-2 adrenergic receptor. More studies are needed to confirm the results and to determine the clinical relevance of these findings.
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Sevoflurane induces neuronal activation and behavioral hyperactivity in young mice
Scientific Reports, 2020Co-Authors: Yuanlin Dong, Yiying Zhang, Lei Yang, Hoai T Ton, Ruohe Zhao, Erez Geron, Guang Yang, Zhongcong XieAbstract:Sevoflurane, a commonly used anesthetic, may cause agitation in patients. However, the mechanism underlying this clinical observation remains largely unknown. We thus assessed the effects of Sevoflurane on neuronal activation and behaviors in mice. Ten-day-old mice received 2% Sevoflurane, 1% isoflurane, or 6% desflurane for 10 minutes. The behavioral activities were recorded and evaluated at one minute after the loss of righting reflex in the mice, which was about two minutes after the anesthetic administration. The neuronal activation was evaluated by c-Fos expression and calcium imaging at one minute after the anesthetic administration. Propofol, which reduces neuronal activation, was used to determine the cause-and-effect of Sevoflurane. We found that Sevoflurane caused an increase in neuronal activation in primary somatosensory cortex of young mice and behavioral hyperactivity in the mice at one minute after the loss of righting reflex. Desflurane did not induce behavioral hyperactivity and isoflurane only caused behavioral hyperactivity with borderline significance. Finally, propofol attenuated the Sevoflurane-induced increase in neuronal activation and behavioral hyperactivity in young mice. These results demonstrate an unexpected Sevoflurane-induced increase in neuronal activation and behavioral hyperactivity in young mice. These findings suggest the potential mechanisms underlying the Sevoflurane-induced agitation and will promote future studies to further determine whether anesthetics can induce behavioral hyperactivity via increasing neuronal activation.
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cyclophilin d contributes to anesthesia neurotoxicity in the developing brain
Frontiers in Cell and Developmental Biology, 2020Co-Authors: Yuanlin Dong, Yiying Zhang, Feng Liang, Ning Liufu, Jialin C Zheng, Zhongcong XieAbstract:Anesthetic Sevoflurane induces mitochondrial dysfunction, impairment of neurogenesis, and cognitive impairment in young mice, but the underlying mechanism remains to be determined. Cyclophilin D (CypD) is a modulatory factor for the mitochondrial permeability transition pore (mPTP). We, therefore, set out to evaluate the role of CypD in these Sevoflurane-induced changes in vitro and in young mice. Wild-type (WT) and CypD knockout (KO) young (postnatal day 6, 7, and 8) mice received 3% Sevoflurane 2 h daily and the neural progenitor cells (NPCs) harvested from the WT or CypD KO mice received 4.1% Sevoflurane. We used immunohistochemistry and immunocytochemistry imaging, flow cytometry, Western blot, RT-PCR, co-immunoprecipitation, and Morris Water Maze to assess the interaction of Sevoflurane and CypD on mitochondria function, neurogenesis, and cognition in vitro and in WT or CypD KO mice. We demonstrated that the Sevoflurane anesthesia induced accumulation of CypD, mitochondrial dysfunction, impairment of neurogenesis, and cognitive impairment in WT mice or NPCs harvested from WT mice, but not in CypD KO mice or NPCs harvested from CypD KO mice. Furthermore, the Sevoflurane anesthesia reduced the binding of CypD with Adenine nucleotide translocator, the other component of mPTP. These data suggest that the Sevoflurane anesthesia might induce a CypD-dependent mitochondria dysfunction, impairment of neurogenesis, and cognitive impairment in young mice and NPCs.
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anesthetic Sevoflurane reduces levels of hippocalcin and postsynaptic density protein 95
Molecular Neurobiology, 2015Co-Authors: Yuanlin Dong, Yiying Zhang, Jie Zhang, Chen Zhou, Zhongcong XieAbstract:Sevoflurane, the commonly used inhalation anesthetic in children, has been shown to enhance cytosolic calcium levels and induce cognitive impairment in young mice. However, the downstream consequences of the Sevoflurane-induced elevation in cytosolic calcium levels and the upstream mechanisms of the Sevoflurane-induced cognitive impairment remain largely to be determined. Hippocalcin is one of the neuronal calcium sensor proteins, and also binds to postsynaptic density protein 95 (PSD-95). We therefore set out to determine the effects of Sevoflurane on the levels of hippocalcin and PSD-95 in vitro and in vivo. Hippocampus neurons from mice and 6-day-old mice were treated with 4.1 % Sevoflurane for 6 h or 3 % Sevoflurane 2 h daily for 3 days, respectively. We then measured the levels of hippocalcin and PSD-95, and assessed whether BAPTA, an intracellular calcium chelator, and memantine, a partial antagonist of the NMDA receptor, could inhibit the Sevoflurane’s effects. We found that Sevoflurane decreased the levels of hippocalcin and PSD-95 in the neurons; and decreased the levels of hippocalcin and PSD-95 in the hippocampus of mice immediately after the anesthesia, but only the PSD-95 levels three weeks after the anesthesia. BAPTA inhibited the Sevoflurane’s effects in the neurons. Memantine attenuated the Sevoflurane-induced reductions in the levels of hippocalcin and PSD-95, as well as the Sevoflurane-induced cognitive impairment in mice. These data suggested that Sevoflurane decreased the levels of hippocalcin and PSD-95, which could serve as one of bridge mechanisms between the Sevoflurane-induced elevation of cytosolic calcium levels and the Sevoflurane-induced cognitive impairment.
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the common inhalational anesthetic Sevoflurane induces apoptosis and increases β amyloid protein levels
JAMA Neurology, 2009Co-Authors: Yuanlin Dong, Robert D. Moir, Guohua Zhang, Bin Zhang, Weiming Xia, Edward R Marcantonio, Deborah J Culley, Gregory CrosbyAbstract:Objective To assess the effects of Sevoflurane, the most commonly used inhalation anesthetic, on apoptosis and β-amyloid protein (Aβ) levels in vitro and in vivo. Subjects Naive mice, H4 human neuroglioma cells, and H4 human neuroglioma cells stably transfected to express full-length amyloid precursor protein. Interventions Human H4 neuroglioma cells stably transfected to express full-length amyloid precursor protein were exposed to 4.1% Sevoflurane for 6 hours. Mice received 2.5% Sevoflurane for 2 hours. Caspase-3 activation, apoptosis, and Aβ levels were assessed. Results Sevoflurane induced apoptosis and elevated levels of β-site amyloid precursor protein–cleaving enzyme and Aβ in vitro and in vivo. The caspase inhibitor Z-VAD decreased the effects of Sevoflurane on apoptosis and Aβ. Sevoflurane-induced caspase-3 activation was attenuated by the γ-secretase inhibitor L-685,458 and was potentiated by Aβ. These results suggest that Sevoflurane induces caspase activation which, in turn, enhances β-site amyloid precursor protein–cleaving enzyme and Aβ levels. Increased Aβ levels then induce further rounds of apoptosis. Conclusions These results suggest that inhalational anesthetic Sevoflurane may promote Alzheimer disease neuropathogenesis. If confirmed in human subjects, it may be prudent to caution against the use of Sevoflurane as an anesthetic, especially in those suspected of possessing excessive levels of cerebral Aβ.
