Sevoflurane Anesthesia In Rats Research Articles

Olfactory bulbectomy leads to prolonged induction phase of sevoflurane anesthesia in rats.

The effect of olfactory bulb lesions on the induction time of sevoflurane has never been studied. We aimed to investigate this issue. In this study, we found that the volume of olfactory bulbs and the pore of the fila olfactoria were significantly lower with the fibrosis of olfactory bulbs in animals subjected to olfactory bulbectomy. Volatile anesthetics induction times were measured in all groups. Prolonged induction was observed in olfactory bulbectomy group. It was concluded that increased induction times of sevoflurane may be due to the olfactory bulb lesion.

Dopaminergic Neurons in the Ventral Tegmental-Prelimbic Pathway Promote the Emergence of Rats from Sevoflurane Anesthesia.

Dopaminergic neurons in the ventral tegmental area (VTA) play an important role in cognition, emergence from anesthesia, reward, and aversion, and their projection to the cortex is a crucial part of the "bottom-up" ascending activating system. The prelimbic cortex (PrL) is one of the important projection regions of the VTA. However, the roles of dopaminergic neurons in the VTA and the VTADA-PrL pathway under sevoflurane anesthesia in rats remain unclear. In this study, we found that intraperitoneal injection and local microinjection of a dopamine D1 receptor agonist (Chloro-APB) into the PrL had an emergence-promoting effect on sevoflurane anesthesia in rats, while injection of a dopamine D1 receptor antagonist (SCH23390) deepened anesthesia. The results of chemogenetics combined with microinjection and optogenetics showed that activating the VTADA-PrL pathway prolonged the induction time and shortened the emergence time of anesthesia. These results demonstrate that the dopaminergic system in the VTA has an emergence-promoting effect and that the bottom-up VTADA-PrL pathway facilitates emergence from sevoflurane anesthesia.

Exogenous insulin-like growth factor 1 attenuates sevoflurane anesthesia-induced cognitive dysfunction in aged rats.

Sevoflurane anesthesia is correlated with the generation of postoperative cognitive dysfunction. Insulin-like growth factor 1 (IGF-1) has important function in the nervous system development. Intravenously injected IGF-1 is reported to successfully pass the blood-brain barrier and perform neuroprotection effect in the brain. Memory and learning abilities were analyzed through Morris water maze task. Relative levels of protein were examined through Western blot and enzyme-linked immunosorbent assay (ELISA). Relative mRNA levels were shown through quantitative real-time polymerase chain reaction (qRT-PCR). IGF-1 expression in the plasma and hippocampus was downregulated in sevoflurane anesthesia-induced rats and rescued by intravenous IGF-1 injection. In aged rats, intravenous injection of IGF-1 alleviated sevoflurane-caused cognitive injuries and elevated TNF-α, IL-1β, and IL-6 levels in the plasma and hippocampus and rescued sevoflurane-depressed Akt phosphorylation. In conclusion, the administration of IGF-1 through intravenous injection alleviates sevoflurane anesthesia-mediated neuroinflammation and cognitive impairment in rats. The effects of IGF-1 in this process may depend on its function in regulating the PI3K/Akt signaling pathway.NEW & NOTEWORTHY IGF-1 expression was downregulated by sevoflurane anesthesia in rats and could be rescued by intravenous IGF-1 injection, which alleviated sevoflurane-caused cognitive injuries and enhanced inflammatory responses in aged rats. Intravenous injection of IGF-1 rescued sevoflurane-depressed Akt phosphorylation in aged rats.

Lithium chloride ameliorates cognition dysfunction induced by sevoflurane anesthesia in rats.

Postoperative cognitive dysfunction is a common complication in elderly patients after surgeries involving anesthesia, but the underlying mechanisms are poorly understood. Lithium is a conventional treatment for bipolar disorder, which exerts a neuroprotective role in various diseases by inhibiting glycogen synthase kinase‐3β (GSK‐3β) in the brain and spinal cord. However, it is not known whether lithium chloride (LiCl) can protect against cognitive dysfunction induced by sevoflurane (SEV) anesthesia. Here, we examined the effects of LiCl on SEV‐induced cognitive dysfunction in rats and on SEV‐induced neuron apoptosis. We report that anesthesia with SEV significantly impaired memory performance, induced oxidative stress and hippocampal neuron apoptosis, and stimulated GSK‐3β activity. Treatment with LiCl ameliorated SEV‐induced cognitive disorder in rats by inhibiting the GSK‐3β/β‐catenin signaling pathway. In addition, LiCl reduced hippocampal neuron apoptosis and oxidative stress induced by SEV anesthesia. These results suggest that LiCl may have potential for development into a therapeutic agent for treatment of SEV anesthesia‐induced cognitive dysfunction.

Effect of acute sleep deprivation on learning and memory and hippocampal circadian gene expression after sevoflurane anesthesia in rats

Objective To investigate the role of clock gene Bmal1, Per2 and Egr1 expression in learning and memory undergoing sevoflurane anesthesia after acute sleep deprivation. Methods 72 male SD rats were equally divided into four groups using a random number table (n=18) : normal control group (group Control), do not do any processing; sleep deprivation group (group SD), acute sleep deprivation for 96 h; sevoflurane group (group Sev), suffering 2.5% sevoflurane for 3 h; sleep deprivation+sevoflurane group (group SD+Sev), 96 h sleep deprivation followed by 3 h 2.5% sevoflurane inhalation. The Morris water maze, for spatial memory acquisition test, was used to measure the time percent of target quadrant and numbers of platform-site crossovers before sleep deprivation (T0) and at 1 d (T1), 3 d (T2), 7 d (T3) after inhalation anesthesia. Rats were sacrificed after spatial memory acquisition test. Brain hippocampus samples were obtained for determination of Bmal1, Per2 and Egr1 expression by Western blot, and neuron morphology was observed by the Nissl staining. Results Compared with Control group, the percentage of time in target quadrant and the numbers of platform-site crossovers were significantly decreased at T1 and T2 in Sev group (P<0.05); and compared with Control group, the percentage of time in target quadrant and the numbers of platform-site crossovers were also significantly decreased at T1, T2 and T3 in SD group rats (P<0.05). Compared with Sev group rats (the percentages of time in target quadrant: T1: (32.37±1.36)%; T2: (30.91±1.26)%; T3: (33.78±2.20)%; the numbers of platform-site crossovers: T1: (4.55±0.39); T2: (3.11±0.37); T3: (3.95±0.34)), the percentages of time in target quadrant (T1: (27.20±1.42)%; T2: (28.19±1.04)%; T3: (30.06±1.22)%) and the numbers of platform-site crossovers (T1: (3.11±0.46); T2: (3.30±0.38); T3: ( 3.20±0.39)) in SD+Sev group rats were significantly decreased at T1, T2 and T3 (all P<0.05). Compared with control group, the levels of hippocampal proteins Bmal1, Per2 and Egr1 were significantly reduced at T1 in Sev group (P<0.05). Compared with control group, the level of hippocampal protein Per2 was significantly increased, but the levels of hippocampal proteins Bmal1 and Egr1 were significantly decreased at T1 and T2 in SD group (P<0.01). Compared with Sev group, the levels of hippocampal proteins Bmal1 and Egr1 were significantly reduced at T1, T2 and T3 in SD+Sev group (P<0.01), and the protein level of hippocampal Per2 was significantly decreased at T1, but then increased at T2 and T3 in SD+Sev group (P<0.01). The hippocampal Nissl staining in CA1 at T2 revealed that there were irregular distribution of pyramidal neurons existed in Sev group, and vacuolar degeneration with vague outlines of pyramidal neurons in SD group, while pyramidal neuron atrophy and few number of Nissl bodies, compared with control group, were observed in SD+Sev group. Conclusion Acute sleep deprivation following with sevoflurane anesthesia resulted in hippocampal memory impairment, which was associated with abnormal expression of hippocampal Bmal1, Per2 and Egr1. Key words: Sleep deprivation; Inhalation anesthesia; Sevoflurane; Learning and memory; Clock gene

セボフルラン麻酔下ラットにおけるモダフィニル静脈内投与による脳波変化(大阪歯科大学大学院歯学研究科博士(歯学)学位論文内容要旨および論文審査結果要旨の公表)

セボフルラン麻酔下ラットにおけるモダフィニル静脈内投与による脳波変化(大阪歯科大学大学院歯学研究科博士(歯学)学位論文内容要旨および論文審査結果要旨の公表)

Ultrastructural changes in the brain cells after discontinuation of sevoflurane anesthesia in rats

Ultrastructural changes in the brain cells after discontinuation of sevoflurane anesthesia in rats

Effects of Naloxone on Opioid-induced Hyperalgesia and Tolerance to Remifentanil under Sevoflurane Anesthesia in Rats

Opioid antagonists at ultra-low doses have been used with opioid agonists to prevent or limit opioid tolerance. The aim of this study was to evaluate whether an ultra-low dose of naloxone combined with remifentanil could block opioid-induced hyperalgesia and tolerance under sevoflurane anesthesia in rats. Male adult Wistar rats were allocated into one of four treatment groups (n = 7), receiving remifentanil (4 µg·kg·min) combined with naloxone (0.17 ng·kg·min), remifentanil alone, naloxone alone, or saline. Animals were evaluated for mechanical nociceptive thresholds (von Frey) and subsequently anesthetized with sevoflurane to determine the baseline minimum alveolar concentration (MAC). Next, treatments were administered, and the MAC was redetermined twice during the infusion. The experiment was performed three times on nonconsecutive days (0, 2, and 4). Hyperalgesia was considered to be a decrease in mechanical thresholds, whereas opioid tolerance was considered to be a decrease in sevoflurane MAC reduction by remifentanil. Remifentanil produced a significant decrease in mechanical thresholds compared with baseline values at days 2 and 4 (mean ± SD, 30.7 ± 5.5, 22.1 ± 6.4, and 20.7 ± 3.7g at days 0, 2, and 4, respectively) and an increase in MAC baseline values (2.5 ± 0.3, 3.0 ± 0.3, and 3.1 ± 0.3 vol% at days 0, 2, and 4, respectively). Both effects were blocked by naloxone coadministration. However, both remifentanil-treated groups (with or without naloxone) developed opioid tolerance determined by their decrease in MAC reduction. An ultra-low dose of naloxone blocked remifentanil-induced hyperalgesia but did not change opioid tolerance under inhalant anesthesia. Moreover, the MAC increase associated with hyperalgesia was also blocked by naloxone.

Changes in the electroencephalogram caused by intravenous administration of modafinil under sevoflurane anesthesia in rats

Changes in the electroencephalogram caused by intravenous administration of modafinil under sevoflurane anesthesia in rats

Propofol anaesthesia alters the cerebral proteome differently from sevoflurane anaesthesia

Previous studies suggest that propofol and sevoflurane anaesthesia in rats may have variable effects on the proteome. Brains from untreated rats and rats anaesthetised with intravenous propofol infusion or inhaled sevoflurane were collected at various time points post-anaesthesia and subjected to global protein expression profiling using two-dimensional gel electrophoresis. Significant changes in protein spot intensity (i.e. expression) between the propofol and sevoflurane groups demonstrated clear similarities and differences in proteomic regulation by these anaesthetics. The proteins regulated were broadly classified into groups involved in cytoskeletal/neuronal growth, cellular metabolism, signalling, and cell stress/death responses. Proteins concerned with cell death and stress responses were down-regulated by both agents, but the anaesthetics had variable effects on proteins in the other groups. Importantly, proteins such as Ulip2 and dihydropyrimidinase-like-2 were regulated in opposite directions by propofol and sevoflurane. Moreover, the time-course of regulation of proteins varied depending on the agent used. These data suggest different underlying mechanisms of proteomic regulation. We found that sevoflurane anaesthesia had more pronounced effects, on a wider range of proteins, and over an apparently longer duration than propofol. Thus, sevoflurane could be considered a more disruptive anaesthetic agent. Our findings show that protein expression is regulated differentially according to the anaesthetic agent and the method of delivery support and extend our previous observations of differential genomic regulation by anaesthetics in the brain. This study highlights the power of proteomic studies in assessing the effects of certain anaesthetics on the integrity of neuronal structure and function.

Activation of orexin signal in basal forebrain facilitates the emergence from sevoflurane anesthesia in rat

Orexinergic system may play an important role in the regulation of anesthesia-arousal. However, which region or which pathway mediated the effect of orexins was still unclear. In current study, we investigated whether activation of orexin signals in basal forebrain (BF) may alter electroencephalographic activity, induction and emergence time to sevoflurane anesthesia in rats. Either orexin-A or orexin-B was injected into the BF while measuring electroencephalogram (EEG) under 1.0 minimum alveolar concentration (2.4%) sevoflurane anesthesia. The induction and emergence time of sevoflurane anesthesia were measured respectively after an injection of orexin receptor agonist (orexin-A or orexin-B) or antagonist (SB-334867A) into the BF also. We found that the administration of orexin-A (30, 100 pmol) and orexin-B (100 pmol) changed the burst and suppression patterns to arousal EEG in rat under sevoflurane anesthesia. Comparing with orexin-B, injection of lower dose of orexin-A induced more arousal EEG. Intrabasalis microinjection of orexin-A shorted the emergence time, whereas intrabasalis microinjection of SB-334867A (5 microg, 20 microg) delayed the emergence time to sevoflurane anesthesia, without changing anesthetic induction. These findings indicate that the orexin signals in basal forebrain, a middle region of the cholinergic ventral ascending arousal system, plays a crucial role in the anesthesia-arousal regulation.

Expression of pulmonary vasoactive factors after sevoflurane anaesthesia in rats: a quantitative real-time polymerase chain reaction study

Sevoflurane is a fluorinated volatile anaesthetic agent that lowers arterial pressure, in part by vasodilation. We previously showed, in rat lungs, that sevoflurane affected the expression of endothelin-1 (ET-1), a potent vasoconstrictor peptide. Therefore, we hypothesized that the vasodilation induced by sevoflurane involved vasodilatory and vasoconstrictor components. Rats were anaesthetized with sevoflurane 4% for 0, 2, and 6 h (n=9 each group) before death. In addition, a further group (n=9) were anaesthetized for 6 h then awoken for 2 h before death (n=9). We measured expression of mRNA encoding ET-1, nitric oxide synthase-1, 2, 3 (NOS1, 2, 3), haeme oxygenase-1, 2 (HO-1, 2), adrenomedullin (ADM), calcitonin gene-related peptide, vasoactive intestinal peptide, and prostacyclin synthase in whole lung using real-time reverse transcriptase-polymerase chain reaction. Expressions of ET-1 and ADM were significantly increased by inhalation of sevoflurane for 2 and 6 h (P<0.05). Expression of NOS3 was significantly increased at 6 h (P<0.05). After awaking from anaesthesia, the expressions of NOS3, ET-1, and ADM returned to baseline levels. Sevoflurane increased the expressions of ET-1, NOS3, and ADM. Our results suggest that the increased expressions of NOS3 and ADM may counteract that of ET-1 and so regulate pulmonary circulation under sevoflurane anaesthesia.

Effect of the neuronal nitric oxide synthase inhibitor 7-nitroindazole on the righting reflex ED50 and minimum alveolar concentration during sevoflurane anaesthesia in rats.

The aim was to determine the effect of acute and chronic administration of 7-nitroindazole, a selective neuronal nitric oxide synthase inhibitor, on the righting reflex ED50 and the minimum alveolar concentration during sevoflurane anaesthesia in rats. 7-Nitroindazole was acutely (0, 50 and 100 mg kg(-1)) and chronically (0 and 150 mg kg(-1) day(-1), 4 days) administered to rats. After the preparation, the minimum alveolar concentration and the righting reflex ED50 were measured. The concentration of cGMP in the brain, cerebellum and spinal cord was also measured. Acute administration reduced the minimum alveolar concentration (50 mg kg(-1), 58.8% (95% CI: 50.3-67.3%) of the baseline value, P < 0.01; 100 mg kg(-1), 55.8 (46.9-64.7), P < 0.01) and the righting reflex ED50 (50 mg kg(-1), 27.2 (17.2-37.2), P < 0.01; 100 mg kg(-1), 14.3 (6.6-22.0), P < 0.01). Chronic administration did not reduce the minimum alveolar concentration; however, it reduced the righting reflex ED50 (65.3 (52.9-77.7), P < 0.01). Overall, the reduction in minimum alveolar concentration in the acute and chronic protocol did not correlate with that of the righting reflex ED50. 7-Nitroindazole (100 mg kg(-1), acute) reduced the cGMP concentration within the cerebellum by 55.4%; however, it did not decrease concentrations in the brain or spinal cord. Different mechanisms are responsible for the observed alterations to the minimum alveolar concentration and the righting reflex ED50 following treatment with 7-nitroindazole. The nitric oxide-cGMP pathway might play a less important role in the determination of minimum alveolar concentration than the righting reflex ED50.

Effect of the neuronal nitric oxide synthase inhibitor 7-nitroindazole on the righting reflex ED50 and minimum alveolar concentration during sevoflurane anaesthesia in rats

Background and objective: The aim was to determine the effect of acute and chronic administration of 7-nitroindazole, a selective neuronal nitric oxide synthase inhibitor, on the righting reflex ED50 and the minimum alveolar concentration during sevoflurane anaesthesia in rats. Methods: 7-Nitroindazole was acutely (0, 50 and 100 mg kg−1) and chronically (0 and 150 mg kg−1 day−1, 4 days) administered to rats. After the preparation, the minimum alveolar concentration and the righting reflex ED50 were measured. The concentration of cGMP in the brain, cerebellum and spinal cord was also measured. Results: Acute administration reduced the minimum alveolar concentration (50 mg kg−1, 58.8% (95% CI: 50.3-67.3%) of the baseline value, P < 0.01; 100 mg kg−1, 55.8 (46.9-64.7), P < 0.01) and the righting reflex ED50 (50 mg kg−1, 27.2 (17.2-37.2), P < 0.01; 100 mg kg−1, 14.3 (6.6-22.0), P < 0.01). Chronic administration did not reduce the minimum alveolar concentration; however, it reduced the righting reflex ED50 (65.3 (52.9-77.7), P < 0.01). Overall, the reduction in minimum alveolar concentration in the acute and chronic protocol did not correlate with that of the righting reflex ED50. 7-Nitroindazole (100 mg kg−1, acute) reduced the cGMP concentration within the cerebellum by 55.4%; however, it did not decrease concentrations in the brain or spinal cord. Conclusions: Different mechanisms are responsible for the observed alterations to the minimum alveolar concentration and the righting reflex ED50 following treatment with 7-nitroindazole. The nitric oxide-cGMP pathway might play a less important role in the determination of minimum alveolar concentration than the righting reflex ED50.

Autoregulation during focal cerebral ischemia under sevoflurane anesthesia in rats

Autoregulation during focal cerebral ischemia under sevoflurane anesthesia in rats

1 ラット局所脳虚血におけるセボフルラン麻酔下での脳循環自己調節能(第473回 大阪歯科学会例会)

1 ラット局所脳虚血におけるセボフルラン麻酔下での脳循環自己調節能(第473回 大阪歯科学会例会)

Room D, 10/17/2000 2: 00 PM - 4: 00 PM (PS) Effect of Nitric Oxide Synthase Inhibitor, 7-Nitro Indazole on the Loss of Righting Reflex during Sevoflurane Anesthesia in Rats

<b>Room D, 10/17/2000 2: 00 PM - 4: 00 PM (PS) Effect of Nitric Oxide Synthase Inhibitor, 7-Nitro Indazole on the Loss of Righting Reflex during Sevoflurane Anesthesia in Rats</b>

Inhibited hypothalamic histamine metabolism during isoflurane and sevoflurane anesthesia in rats.

Histamine is most densely distributed in the hypothalamus and has an important effect on consciousness or wakefulness. It has been little considered whether general anesthetics could exert their effects on hypothalamic histamine metabolism. The present study was conducted to investigate the effects of isoflurane and sevoflurane anesthesia on hypothalamic histamine metabolism. Sixty male Wistar rats were divided equally into isoflurane and sevoflurane anesthesia groups. Each group was divided into three equal sub-groups: the control, anesthesia and recovery groups. The rats of the anesthesia and recovery groups were exposed to either 2% isoflurane or 3% sevoflurane for 30 min. The recovery group was kept in air for 30 min after anesthesia. The rats were decapitated to dissect out hypothalamus which was divided into the fore and rear portion. The contents of histamine and 1-methylhistamine, which is a main histamine metabolite, were determined by high-performance liquid chromatography. The obtained data were analyzed by one-way analysis of variance followed by Bonferoni's test. Histamine contents of the anterior and posterior hypothalamus in both isoflurane and sevoflurane groups increased significantly during the anesthesia and 1-methylhistamine contents of the anterior and posterior hypothalamus in sevoflurane group increased remarkably after anesthesia. The increases of histamine contents supposedly reflected inhibited histamine metabolism and the increases of 1-methylhistamine would be caused by acceleration of histamine degradation. Histamine metabolism was inhibited during both isoflurane and sevoflurane anesthesia and accelerated only in the posterior hypothalamus during the emergence from these anesthetics.

Posterior Hypothalamic Noradrenaline Release During Emergence from Sevoflurane Anesthesia in Rats

Posterior Hypothalamic Noradrenaline Release During Emergence from Sevoflurane Anesthesia in Rats

Posterior hypothalamic noradrenaline release during emergence from sevoflurane anesthesia in rats.

Posterior hypothalamic noradrenaline release during emergence from sevoflurane anesthesia in rats.