Effects Of Sevoflurane Anesthesia Research Articles

Effect of Sevoflurane Anesthesia on Diastolic Function: A Prospective Observational Study.

The effect of sevoflurane on left ventricular diastolic function is not well understood. We hypothesized that parameters of diastolic function may improve under sevoflurane anesthesia in patients with preexisting diastolic dysfunction compared to patients with normal diastolic function. This observational study included 60 patients undergoing breast surgery or laparoscopic cholecystectomy. Patients were assigned to diastolic dysfunction (n = 34) or normal (n = 26) groups of septal e' < 8 or ≥ 8.0 cm/s on the first thoracic echocardiography (TTE) performed before anesthesia. During anesthesia, sevoflurane was maintained at 1 to 2 minimum alveolar concentration (MAC) to maintain the bispectral index at 40 to 50. At the end of surgery, the second TTE was performed under 0.8 to 1 MAC of sevoflurane with the patient breathing spontaneously without ventilator support. Primary end point was the percentage change (Δ) of e' on 2 TTEs (Δe'). Secondary end points were ΔE/e', Δleft atrial volume index (ΔLAVI), and Δtricuspid regurgitation maximum velocity (ΔTR Vmax). These percentage changes (Δ) were compared between diastolic dysfunction and normal groups. e' (Δe': 30 [6, 64] vs 0 [-18, 11]%; P < .001), mitral inflow E wave velocity (E), mitral inflow E/A ratio (E/A), and mitral E velocity deceleration time (DT) improved significantly in diastolic dysfunction group compared to normal group. LAVI decreased in diastolic dysfunction group but did not reach statistical significance between the 2 groups (ΔLAVI:-15 [-31, -3] vs -4 [-20, 10]%, P = .091). ΔE/e' was not different between the 2 groups (11 [-16, 26] vs 12 [-9, 22]%, P = .853) (all: median [interquartile range, IQR]). TR was minimal in both groups. In this study, echocardiographic parameters of diastolic function, including septal e', E, E/A, and DT, improved with sevoflurane anesthesia in patients with preexisting diastolic dysfunction, but remained unchanged in patients with normal diastolic function.

Medial Septal Glutamatergic Neurons Modulate States of Consciousness during Sevoflurane Anesthesia in Mice.

Multiple neural structures involved in maintaining wakefulness have been found to promote arousal from general anesthesia. The medial septum is a critical region that modulates arousal behavior. This study hypothesized that glutamatergic neurons in the medial septum play a crucial role in regulating states of consciousness during sevoflurane general anesthesia. Adult male mice were used in this study. The effects of sevoflurane anesthesia on neuronal activity were determined by fiber photometry. Lesions and chemogenetic manipulations were used to study the effects of the altered activity of medial septal glutamatergic neurons on anesthesia induction, emergence, and sensitivity to sevoflurane. Optogenetic stimulation was used to observe the role of acute activation of medial septal glutamatergic neurons on cortical activity and behavioural changes during sevoflurane-induced continuous steady-state of general anesthesia and burst suppression state. We found that medial septal glutamatergic neuronal activity decreased during sevoflurane anesthesia induction and recovered in the early period of emergence. Chemogenetic activation of medial septal glutamatergic neurons prolonged the induction time (mean ± SD, hM3Dq-Clozapine N-oxide vs. hM3Dq-Saline, 297.5 ± 60.1 s vs. 229.4 ± 29.9 s, P < 0.001, n = 11) and decreased the emergence time (53.2 ± 11.8 s vs. 77.5 ± 33.5 s, P = 0.025, n = 11). Lesions or chemogenetic inhibition of these neurons produced the opposite effects. During steady-state of general anesthesia and deep anesthesia-induced burst suppression state, acute optogenetic activation of medial septal glutamatergic neurons induced cortical activation and behavioural emergence. Our findings reveal that activation of medial septal glutamatergic neurons has arousal-promoting effects during sevoflurane anesthesia in male mice. The activation of these neurons prolongs the induction and accelerates the emergence of anesthesia.

Effects of Sevoflurane Anesthesia on Cerebral Lipid Metabolism in the Aged Brain of Marmosets and Mice.

ObjectiveIn the lipid-rich brain, lipids performed signaling processes associated with the control system of the cell cycle, stress, and inflammatory reactions, as well as maintained brain and cellular homeostasis. The effects of general anesthesia on brain impairment in the elderly were controversial and complex. The study sought to evaluate the effect of lipid metabolism in the brain of aged marmosets and mice under long-term exposure to sevoflurane.MethodsA total of 6 marmosets over 8-year-old and 10 mice aged 18 months were divided into the sevoflurane anesthesia and control groups, respectively. Marmosets in the sevoflurane anesthesia group were exposed to 1.5–2.5% sevoflurane and 100% O2 for 6 h. Mice anesthetized with sevoflurane were exposed to 3% sevoflurane and 60% O2 for 6 h. All prefrontal cortex tissues of marmosets and mice were harvested for the analysis of lipidomics.ResultsCompared to the control group, we found that phosphatidylethanolamine (PE) (18:0/22:5), PE (16:0/22:5), PE (18:2/22:5), PE (14:0/22:5), and PE (18:1/22:5) increased in the prefrontal cortex of marmosets in the sevoflurane group, while triglyceride (TAG)56:5-fatty acid (FA) 20:4, TAG58:10-FA22:6, and TAG60:10-FA22:6 decreased. For aged mice, we indicated that lipid components phosphatidic acid (PA) (18:1/20:2) and TAG52:5-FA20:4 in the sevoflurane group increased, but PE (14:0/22:4), diglyceride (DAG) (16:1/18:2), and lysophosphatidylcholine (LPC) (16:1) + AcO decreased. More deeply, sevoflurane anesthesia resulted in the presence of 70 specific lipids in mice and marmosets. The enriched lipid subclasses were mainly monoacylglycerophosphoethanolamines and five other subclasses.ConclusionSevoflurane caused slight changes in lipid metabolism both in the aged brain of marmosets and mice. However, the pathways of lipid metabolism were not affected. The effects of sevoflurane on lipid metabolism in aged brains may differ among species.

The Effect of Sevoflurane Anesthesia on the Biomarkers of Neural Injury in the Prefrontal Cortex of Aged Marmosets.

BackgroundSurgery under general anesthesia leads to neural injury, especially in older patients. Sevoflurane anesthesia without surgery for 2 h does not induce neural injury, however, whether prolonger sevoflurane anesthesia without surgery has the same consequence is still unknown.MethodsIn the present study, aged marmosets were exposed to a clinical concentration of sevoflurane (1.5–2%) for 6 h to access the effects of prolonged sevoflurane anesthesia on the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), Caspase3 activity and myelin formation in the brain.ResultsSevoflurane anesthesia did not alter the expression of IL-6 (120.1 ± 2.21 vs. 120.8 ± 2.25, p = 0.74), TNF-α (189.3 ± 31.35 vs. 218.7 ± 21.47, p = 0.25) and Caspase3 (57.35 ± 1.54 vs. 58.67 ± 1.19, p = 0.53) in the prefrontal cortex (PFC) of aged marmosets. The amount of MBP expression (60.99 ± 6.21 vs. 58.91 ± 2.71, p = 0.77) did not change following sevoflurane exposure.ConclusionSevoflurane anesthesia did not increase the levels of IL-6 and TNF-α, activated the the expression of Caspase3, and induced myelination deficits in the PFC of aged marmosets.

PP2A-associated tau hyperphosphorylation was involved in sevoflurane induced neonatal neurotoxicity.

The effects of sevoflurane anesthesia on childhood neurodevelopment and adult brain function have attracted increasing scientific attentions. However, the exact mechanisms underlying hyperphosphorylation of tau protein in sevoflurane induced abnormalities in central nervous system (CNS) development, particularly in the hippocampus, have not been fully determined. We utilized molecular biological and behavioral approaches to compare the changes in cognitive function in mice exposed to repeated sevoflurane during the neonatal stage, and to assess whether PP2A-associated tau hyperphosphorylation is involved in sevoflurane induced neonatal neurotoxicity. We reported that mice anesthetized with repeated sevoflurane during the neonatal period caused cognitive dysfunction during the adulthood. More importantly, we found that hyperphosphorylation of tau protein and decreased level of protein phosphatase 2A (PP2A) were detected in the hippocampus of mice after neonatal exposure of sevoflurane. Meanwhile, GSK-3β activity was found to be increased with repeated sevoflurane exposure, but not for more than 2weeks. Our results suggest that PP2A-associated hyperphosphorylation of tau protein might contribute to sevoflurane induced developmental neurotoxicity. These findings could provide a theoretical basis for the safely usage of sevoflurane in pediatric surgeries, and offer a valuable reference and potential therapeutic targets for the development of neuroprotective drugs.

Participation of Mind Bomb-2 in Sevoflurane Anesthesia Induces Cognitive Impairment in Aged Mice via Modulating Ferroptosis.

Postoperative cognitive dysfunction (POCD) is a complication of the central nervous system (CNS) often occurred after surgery or anesthesia in the elder patients. Mind bomb-2 (MIB2) has been reported to modulate neuronal functions. Here, we aimed to study whether MIB2 exerts roles in the effects of sevoflurane anesthesia on mice hippocampal neurons and function, and how. Aging male C57BL/6 mice were subjected to sevoflurane administration, and primary hippocampal neurons were adopted to study sevoflurane effects in vitro. Western blotting and immunohistochemistry assay were used to study the protein expression of MIB2. CCK-8 assay and propidium iodide (PI) staining were performed to evaluate cell viability and cell death, respectively. Ferroptosis-related indicators malondialdehyde (MDA), glutathione (GSH), and iron levels were checked through indicated ELISA kits. Co-immunoprecipitation was adopted to study the binding effects of MIB2 to GPX4. We found that sevoflurane anesthesia increased MIB2 expression in mice hippocampus tissues and neurons. Knockdown of MIB2 alleviated neuron death and ferroptosis induced by sevoflurane exposure. Downregulated MIB2 enhanced GPX4 stability and reduced its ubiquitination. MIB2 was verified to bind to GPX4. The effects of MIB2 knockdown on the neuron death and ferroptosis can be reversed by further siGPX4 transfection. In vivo results also showed that MIB2 knockdown reduced hippocampal neuron death, ferroptosis, and cognitive impairments in the sevoflurane-exposed mice. Taking all together, downregulation of MIB2 could alleviate the sevoflurane-anesthesia-induced cognitive dysfunction and neuron injury through reducing ferroptosis via GPX4. Our results also provide novel directions for POCD treatment using anti-MIB2-related drugs or strategies.

Effects of sevoflurane anesthesia and abdominal surgery on the systemic metabolome: a prospective observational study

BackgroundMetabolic status can be impacted by general anesthesia and surgery. However, the exact effects of general anesthesia and surgery on systemic metabolome remain unclear, which might contribute to postoperative outcomes.MethodsFive hundred patients who underwent abdominal surgery were included. General anesthesia was mainly maintained with sevoflurane. The end-tidal sevoflurane concentration (ETsevo) was adjusted to maintain BIS (Bispectral index) value between 40 and 60. The mean ETsevo from 20 min after endotracheal intubation to 2 h after the beginning of surgery was calculated for each patient. The patients were further divided into low ETsevo group (mean − SD) and high ETsevo group (mean + SD) to investigate the possible metabolic changes relevant to the amount of sevoflurane exposure.ResultsThe mean ETsevo of the 500 patients was 1.60% ± 0.34%. Patients with low ETsevo (n = 55) and high ETsevo (n = 59) were selected for metabolomic analysis (1.06% ± 0.13% vs. 2.17% ± 0.16%, P < 0.001). Sevoflurane and abdominal surgery disturbed the tricarboxylic acid cycle as identified by increased citrate and cis-aconitate levels and impacted glycometabolism as identified by increased sucrose and D-glucose levels in these 114 patients. Glutamate metabolism was also impacted by sevoflurane and abdominal surgery in all the patients. In the patients with high ETsevo, levels of L-glutamine, pyroglutamic acid, sphinganine and L-selenocysteine after sevoflurane anesthesia and abdominal surgery were significantly higher than those of the patients with low ETsevo, suggesting that these metabolic changes might be relevant to the amount of sevoflurane exposure.ConclusionsSevoflurane anesthesia and abdominal surgery can impact principal metabolic pathways in clinical patients including tricarboxylic acid cycle, glycometabolism and glutamate metabolism. This study may provide a resource data for future studies about metabolism relevant to general anaesthesia and surgeries.Trial registrationwww.chictr.org.cn. identifier: ChiCTR1800014327.

The effects of sevoflurane anesthesia on hemodynamics and cerebral artery diameters in endovascular treatment of intracranial aneurysm: A pilot study.

Cerebral autoregulation is a steady-state of cerebral blood flow despite major changes in arterial blood pressure. Inhalation anesthetics are cerebral vasodilators. In <1 MAC values, the net effect is a moderate decrease in cerebral blood flow and maintenance of responsiveness to carbon dioxide. This study aims to investigate the effects of steady-state sevoflurane anesthesia on hemodynamic and cerebral artery diameter measurements in patients undergoing flow diverter device placement under general anesthesia. Forty-six patients aged 18-70 years who underwent flow diverter devices under general anesthesia were included in this study. Routine monitoring was performed on the patients. Mean arterial pressure (MAP) values were recorded. Internal carotid artery, middle cerebral artery and anterior cerebral artery diameter measurements were made from digital subtraction angiography (DSA) images of patients with anterior aneurysms. Baseline artery, right posterior cerebral artery and left posterior cerebral artery diameter measurements were made from DSA images of patients with posterior aneurysms. These measurements were recorded as preoperative measurements. The same measurements were made from the DSA images performed before the Flow diverter device placement procedure performed under steady-state sevoflurane anesthesia for the same patients. These measurements were recorded as peroperative measurements. The average age of the patients was 56.6±15.1. The MAP of the patients before induction was 76.28±5.13 mmHg, MAP after induction was 64.36±3.23 mmHg, and MAP during sevoflurane anesthesia was 68.26±4.30 mmHg, there was a statistically significant difference. There was a statistically significant difference between the preoperative and perioperative values of anterior cerebral artery diameters. There was a strong relationship between the MAP change percentage and the ICA diameter change percentage (p<0.001, p=-0.785) and a moderate relationship between the MCA diameter change percentage (p=0.033, p=-0.338). In patients undergoing flow diverter devices, <1 MAC sevoflurane has a hemodynamic effect and creates significant vasodilation in the cerebral artery diameters.

Effects on the Lipid Peroxidation and the Antioxidant Defense Systems of the Use of Isoflurane or Sevoflurane in Calves Undergoing Surgery

Background: Incoming anaesthesia created by the use of many drugs with different physicochemical properties is a source of stress and trauma for the body. This event increases the oxidative response and changes the balance between oxidant/antioxidant capacity in the organism in favor of oxidant capacity. This situation is defined as oxidative stress. For these reasons, studies are conducted to determine the effects of general anaesthetic agents on oxidant and antioxidant systems in the organism. In this study, it was aimed to determine the effects of isoflurane and sevoflurane used for general anaesthesia in humans and animals on lipid peroxidation and antioxidant defense system in calves.Materials, Methods &amp; Results: The study included 14 calves of different breeds, ages, sexes, and weighing, average 2 weeks old. The cases randomly were divided into 2 groups, the isoflurane group (group I), and the sevoflurane group (group II), and each group included 7 animals. Before general anaesthesia, 0.04 mg/kg atropine was administered intramuscularly to all animals for premedication. At 15 min after atropine administration, isoflurane was administered at an inspiratory concentration of 3-5% in group I, and sevoflurane was administered at an inspiratory concentration of 5-7% in group II, via a face mask for 15 min for the induction of anaesthesia. Endotracheal intubation was performed in all cases at the 15min of the induction period following the onset of general anaesthesia symptoms. After the induction, anaesthesia was continued at an inspiratory concentration of 1.5-3% in the isoflurane group and inspiratory concentration of 2.5-4% in the sevoflurane group. Blood samples were taken just before anaesthesia, just before skin incision, at the end of anaesthesia and surgery, and at the 24h postoperatively. The malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione (GSH) levels were measured spectrophotometrically in samples. In group I, MDA and antioxidant parameters SOD, CAT, GSH-Px, GSH did not observe a significant change in their concentrations through the study (P &gt; 0.05). In group II, MDA value decreased significantly before incision (P &lt; 0.05), at the end of anaesthesia and surgery compared to the pre-anaesthesia level (P &lt; 0.001), and then although increased significantly at 24th-h postoperatively, the value was still lower than the pre-anaestesia level (P &lt; 0.05). It was determined that SOD activity increased significantly after sevoflurane compared to pre-anaesthesia (P &lt; 0.05) however, the increases in SOD activity detected during sevoflurane were not statistically significant (P &gt; 0.05). During the study, a statistically insignificant increase was observed in the concentrations of CAT, GSH-Px, GSH compared to pre-anaesthesia (P &gt; 0.05). Pre-anaesthesia values of all measured biochemical parameters did not differ significantly between groups (P &gt; 0.05). Before skin incision, at the end of anaesthesia and surgery, and at the 24h postoperatively MDA was lower (P &lt; 0.05) and SOD activity was higher (P &lt; 0.05) than in group I in group II. There was no statistically significant difference between the two groups in terms of CAT, GSH-Px, GSH levels between the other measurement times (P &gt; 0.05). Discussion: An important advantage of sevoflurane compared to currently available anaesthetics is that it provides rapid induction due to its low solubility in blood and tissues, and rapid recovery due to its low solubility in fat. This feature is proof that the side effects of sevoflurane anaesthesia are minimal. The findings of this study show that sevoflurane exposure decreases lipid peroxidation and enhances antioxidant defense. The potential effect of sevoflurane on oxidative stress may lead to its preferred clinical use of sevoflurane compared to isoflurane.

Effect of sevoflurane anaesthesia on nasal mask in endoscopic retrograde cholangiopancreatography: is it a preferred alternative?

Background/aimEndoscopic retrograde cholangiopancreatography (ERCP) often requires deep sedation. Propofol provides adequate sedation and amnesia at subhypnotic doses, but safe guarding the patient’s airway is important for preventing respiratory depression or u28ba events. This study compared sedation levels, operator satisfaction, intraoperative and recovery characteristics using sevoflurane with nasal mask and propofol in ERCP.Material and methodsSixty-one patients underwent ERCP (Group I: propofol, n = 31; Group II, sevoflurane, n = 30), with sedation controlled by the Ramsay sedation scale (RSS). The patients’ demographic data, procedure length, overall drug dose, hemodynamic changes, duration of recovery and Aldrete scores during recovery were evaluated. In addition, satisfaction of the gastroenterologist was evaluated.ResultsThe mean sphincterotomy satisfaction scores were statistically significant (P= 0.043). The Aldrete scores and RSS of the groups were similar; there was a significant difference between groups at the beginning of the procedure regarding peripheric oxygen saturations and Group II’s saturation levels increased during sedation.Conclusion In ERCP, propofol infusion provides shorter recovery duration and adequate sedation levels. Sevoflurane and oxygen with a nasal mask can be chosen to generate specific anaesthesia in patients, especially for strong airway support and safety treating hypoxemic patients.

Anesthetic effect of sevoflurane in the craniotomy hematoma evacuation treatment of hypertensive cerebral hemorrhage.

Anesthetic effect of sevoflurane in the craniotomy hematoma evacuation treatment of hypertensive cerebral hemorrhage.

The effect and possible mechanism of sevoflurane exposure on electroencephalographic seizures and long-term cognitive function in neonatal rats

Objective To investigate the effect of sevoflurane anesthesia on electroencephalographic (EEG) seizures and long-term behavior and possible mechanism in neonatal rats. Methods A total of 141 postnatal days 4-6 Sprague-Dawley rats (66 male, 75 female) were divided into 3 groups (n=47 in each group) according to random number table method: control group, sevoflurane group, and NKCC1 inhibitor group, with 22 males and 25 females in each group. Rats in the control group were fed in normal cage without anesthesia; rats in the sevoflurane group were anesthetized with 2.1% sevoflurane for 6 hours; rats in the NKCC1 blocker group received intraperitoneal injection of 1.82 mg / kg bumetanide 30 minutes before anesthesia with 2.1% sevoflurane. The rats in the control group and sevoflurane group were injected subcutaneously with the same dose of DMSO at the same time when the NKCC1 blocker group received the drug intervention, so as to eliminate the influence caused by the solvent. The rats were observed for 30 minutes after recovery from anesthesia and then continued to breastfeed normally. Some of the new born rats received EEG monitoring from 9 to 11 days after being raised; the other rats received EPM and PPI respectively at 60 and 70 days after being raised. Results The results of EEG showed that, compared with the control group, the number of epileptic waves((0.429±0.787), (1.571±0.787), t=2.753, P 0.05). Compared with male rats, the average duration of female rats in sevoflurane group decreased ((6.392±3.374), (2.515±2.992), t=3.044, P 0.05). Comparison between male and female rats: compared with male rats in sevoflurane group, the female rats in sevoflurane group had a longer open arm stay time in EPM experiment (P<0.05), the difference was statistically significant. Conclusion Sevoflurane anesthesia for 6 hours can significantly increase the generation of epileptic waves in EEG of male newborn rats, and cause behavioral abnormalities in adult male rats, which may be related to NKCC1.And male rats are more vulnerable to the negative effects of sevoflurane anesthesia on brain nerve development. Key words: Sevoflurane; Neonatal anesthesia; Bumetanide; Gender; Electroencephalo-graphic; Behaviour; Rat

Effect of sevoflurane maintenance anesthesia on liver ischemia-reperfusion injury in patients undergoing partial hepatectomy

Objective To investigate the effect of sevoflurane anesthesia on hepatic ischemia-reperfusion injury in patients undergoing partial hepatectomy. Methods A total of 86 patients undergoing partial hepatectomy were divided into sevoflurane group and isoflurane group according to random number table with 43 patients in each group. Both groups received continuous epidural block combined with general anesthesia, sevoflurane group took sevoflurane combined with remifentanil to maintain anesthesia, while isoflurane group took isoflurane remifentanil to maintain anesthesia. The mean arterial pressure (MAP) and heart rate(HR) of different moments, awakening (open-eye time, extubation time, listening to instruction time, orientation recovery time, time of Aldrete score up to 9 minutes), the serum levels of tumor necrosis factor alpha (TNF-α), interleukin 1 (IL-1), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH), alpha glutathione S transferase (α-GST) levels at different moments were compared between the two groups. Results The MAP and HR at T1, T2, T3 and T4 in both groups were significantly lower than those at T0 (P<0.05). The HR at T1 and T4 in sevoflurane group were significantly higher than those in isoflurane group (P<0.05). The open-eye time, extubation time, listening to instruction time, orientation recovery time in sevoflurane group were significantly shorter than the isoflurane group (P<0.05). The levels of serum TNF-α, IL-1, AST, ALT, GLDH and α-GST in the two groups at T2 and T3 were significantly higher than those at T0 (P<0.05), and began to fall back to T4. The levels of serum TNF-α, IL-1, AST, ALT, GLDH and α-GST in the sevoflurane group at T2 and T3 were significantly lower than those in the isoflurane group (P<0.05). Conclusions The hepatic hemodynamics in patients undergoing partial hepatectomy with sevoflurane is more stable better than isoflurane during operation, which has faster postoperative recovery and relieved hepatic ischemia-reperfusion injury. Key words: Hepatectomy; Sevoflurane; Reperfusion injury; Hemodynamics

Hemin treatment protects neonatal rats from sevoflurane-induced neurotoxicity via the phosphoinositide 3-kinase/Akt pathway

AimsAnaesthesia-related neurotoxicity in the developing brain is a controversial issue that has recently attracted much attention. Hemin plays a protective role in hypoxic and ischemic brain damage; however, its effects on sevoflurane-induced neurotoxicity remain unclear. Our aim was to investigate the mechanisms of sevoflurane neurotoxicity and potential neuroprotective roles of hemin upon sevoflurane exposure. Main methodsHippocampi were harvested 18 h after sevoflurane exposure. Haem oxygenase 1 (HMOX1), superoxide dismutase 2 (SOD2), discs large MAGUK scaffold protein 4 (DLG4), phosphorylated Akt, Akt, cleaved caspase 3, and neuroglobin were detected by western blotting. A water maze test was used to assess learning and memory ability in P30 rats. Key findingsSevoflurane inhalation increased cleaved caspase 3 levels. Hemin treatment enhanced the antioxidant defence response, protecting rats from oxidative stress injury. Hemin plays its neuroprotective role via phosphoinositide 3-kinase (PI3K)/Akt signalling. A single inhalation of sevoflurane did not affect DLG4 expression, while hemin treatment did. Platform crossing increased in rats treated with hemin as well, which may be related to increased DLG4. Neuroglobin expression was not affected, suggesting that it may act upstream of PI3K/Akt signalling. SignificanceOur study demonstrates that hemin plays a protective role in anaesthesia-induced neurotoxicity by both inhibiting apoptosis via the PI3K/Akt pathway and increasing the expression of antioxidant enzymes, reducing oxidative damage. The results provide mechanistic insight into the effects of sevoflurane anaesthesia on the developing brain and suggest that hemin could help avoid these effects.

Effect of sevoflurane anesthesia on cognitive impairment in rats with traumatic brain injury

Objective To evaluate the effect of sevoflurane anesthesia on cognitive impairment in rats with traumatic brain injury. Methods One hundred and and twenty healthy male Wistar rats, aged 2-3 months, weighing 190-220 g, were assigned into 4 groups (n=30 each) using a random number table method: control group (group C), traumatic brain injury group (group T), sevoflurane anesthesia group (group S), and traumatic brain injury plus sevoflurane anesthesia group (group T+ S). A 40 g hammer was freely dropped onto the left parietal bone window from a height of 20 cm to establish the traumatic brain injury model in T and T+ S groups.Twelve days later, S and T+ S groups inhaled 3% sevoflurane for 3 h, and C and T groups inhaled pure oxygen for 3 h. On 1 day before anesthesia and 3 and 7 days after anesthesia, 10 rats in each group were randomly selected for performing Morris water maze test.Rats were sacrificed after the end of Morris water maze test, and the hippocampal tissues were obtained for determination of the apoptosis rate of hippocampal neurons, cytoplasmic calcium concentration [Ca2+ ]i (by flow cytometry), expression of glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP) (by immunohistochemistry), and expression of caspase-3 and caspase-12 (by Western blot). Results Compared with group C, the escape latency was significantly prolonged, the number of crossing platform was decreased, the apoptosis rate of hippocampal neurons and [Ca2+ ]i were increased, and the expression of caspase-3, caspase-12, GRP78 and CHOP in hippocampal tissues was up-regulated in S, T and T+ S groups (P<0.05). Compared with T and S groups, the escape latency was significantly prolonged, the number of crossing platform was decreased, the apoptosis rate of hippocampal neurons and [Ca2+ ]i were increased, and the expression of caspase-3, caspase-12, GRP78 and CHOP in hippocampal tissues was up-regulated in group T+ S (P<0.05). Conclusion Sevoflurane anesthesia can accentuate cognitive impairment in rats with traumatic brain injury, and the mechanism may be related to aggravating the degree of endoplasmic reticulum stress-induced calcium overload and increasing the apoptosis rate of hippocampal neurons. Key words: Anesthetics, inhalation; Brain injuries, traumatic; Cognition disorders

The effect of sevoflurane anesthesia on learning and memory and hippocampal histone acetylation in mice

Objective To investigate the effect of sevoflurane anesthesia on learning and memory in mice and the relationship with histone acetylation. Methods Thirty-six adult male C57BL/6 mice were randomly divided into control group(mice inhaled 95% O2 for 6 h), sevoflurane (Sevo) group (1.5% Sevo group, 2% Sevo group, 3% Sevo group: mice inhaled 1.5%, 2% and 3% sevoflurane for 6 h respectively), sevoflurane + SAHA (Sevo + SAHA) group (mice were intraperitoneally injected with histone deacetylase inhibitor SAHA (25 mg/kg). And 1 h later, 3% Sevo was inhaled continuously for 6 hours.)and SAHA group(mice were intraperitoneally injected with histone deacetylase inhibitor SAHA (25 mg/kg)). The ability of learning and memory in mice was estimated by Morris water maze. The expression levels of Ac-H3, BDNF and Syt-I protein in the hippocampus were detected by Western blot. Results In Morris water maze, 3% sevoflurane anesthesia significantly prolonged the escape latency((46.91±1.84)s), and significantly decreased the ratio of target time((35.84±5.40)%) compared with that of control group((23.46±2.67)s, (49.74±4.91)%, P<0.05). Compared with 3% Sevo group, the ratio of target time in Sevot+ SAHA group((46.86±4.37)%) was increased(P<0.05). Moreover, 3% sevoflurane anesthesia significantly decreased the expression levels of Ac-H3 (10.23±2.45), BDNF (6.72±1.21) and Syt-I (8.25±2.11) in the hippocampus compared with that of control group((15.45±2.58), (10.17±1.45) and (15.02±3.38), P<0.05). However, pre-administration of the histone deacetylase inhibitor SAHA significantly increased the ratio of target time in Morris water maze, and improved the expression levels of Ac-H3 (14.06±2.79), BDNF (10.13±1.06) and Syt-I (14.16±3.66) in Sevo+ SAHA group compared with that of Sevo group (P<0.05). Conclusion The high dose of sevoflurane anesthesia can induce learning and memory impairment through the inhibitation of histone acetylation in the hippocampus. Key words: Sevoflurane; Histone acetylation; Learning and memory

Sevoflurane reduced functional connectivity of excitatory neurons in prefrontal cortex during working memory performance of aged rats

BackgroundSevoflurane has been found to increase apoptosis and pathologic markers associated with Alzheimer disease, provoking concern over their potential contribution to postoperative cognitive dysfunction. This study aimed to evaluate the effects of sevoflurane on working memory of rats and to characterize functional connectivity between excitatory neurons in the prefrontal cortex (PFC) during working memory performance. Methods18-month-old and 3-month-old male SD rats were implanted with a multielectrode array in the PFC. After recovery from the surgery, the aged and adult rats were divided into sevoflurane group and control group, respectively. Rats in sevoflurane group were exposed to 1 minimum alveolar concentration (MAC) or 1.5 MAC sevoflurane for two hours. At day1, 3, and 7 after exposure, the effects of sevoflurane anesthesia on working memory were investigated in the aged and adult rats by using delayed alternation in Y-maze. Spike trains of excitatory neurons in the PFC were recorded with the multielectrode array while rats were undergoing working memory performance. Functional connectivity between PFC excitatory neurons was described by Granger causal connectivity analysis. ResultsIn adult rats, 1.5 MAC sevoflurane reduced working memory and functional connectivity between PFC excitatory neurons at day1 after exposure (P < 0.01). However, in aged rats, 1.5 MAC sevoflurane reduced working memory and functional connectivity between PFC excitatory neurons at day1, 3, and 7 after exposure (P < 0.01). 1 MAC sevoflurane reduced working memory and functional connectivity between PFC excitatory neurons of aged rats at day1 after exposure (P < 0.01), but it had no effect in adult rats. ConclusionsSevoflurane-induced working memory impairment may depend on advanced age and anesthetic concentration. These findings also suggest, in rats, that sevoflurane-induced working memory impairment may be related to the decreased functional connectivity between PFC excitatory neurons.

Effect of Sevoflurane Anesthesia on Brain Is Mediated by lncRNA HOTAIR.

Postoperative cognitive dysfunction in elderly patients has been related to neurodegenerative disorders and mortality. Sevoflurane anesthesia has been implicated in both postoperative cognitive dysfunction and neurotoxicity. Given the advantages of using inhaled anesthetics like sevoflurane, it is important to understand how their usage results in neurotoxicity and subsequently devise ways to circumvent or attenuate the anesthetic-mediated induction in neurotoxicity. Long noncoding RNAs (LncRNAs) are a group of > 200bp long RNAs and show specific spatiotemporal expression profiles. Several recent reports suggest that lncRNAs are involved in responses of the central nervous system (CNS) following acute injuries. However, their role in sevoflurane anesthesia-mediated cognitive dysfunction has not been studied. RNA immunoprecipitation (RIP) combined with qRT-PCR detection of six different lncRNAs showed that the HOTAIR lncRNAs were significantly more bound to both Sin3A and coREST, both corepressors of the RE-1 silencing transcription factor, within rat hippocampus following sevoflurane anesthesia compared with sham. Sevoflurane inhalation resulted in significant inhibition of brain-derived neurotrophic factor (BDNF) and cognitive impairment. Treatment with a combination of siRNAs targeting HOTAIR rescued BDNF expression and improved cognitive responses. Taken together, our results suggest that sevoflurane-mediated brain function impairment is at least in part mediated by the HOTAIR lncRNA.

Determination of the Effects of Sevoflurane Anesthesia in Different Maturing Stages of the Mouse Hippocampus by Transcriptome Analysis

Purpose: Postoperative cognitive dysfunction (POCD) is a serious complication after general anesthesia. POCD is more likely to occur in elderly patients, but the mechanism of POCD has not been fully elucidated. We hypothesized that the difference of mRNA expression profile in the brain depending on the maturing stage causes the difference in the effect of sevoflurane anesthesia. We investigated the mRNA expression profile of hippocampal cells in young mice and in aged mice under sevoflurane anesthesia using transcriptome analysis. Methods: This study was conducted after approval from our institutional animal ethics committee, the Animal Research Center of Sapporo Medical University School of Medicine (project number: 12-033). Eight mice were assigned to two groups: a young group and an aged group. Each of the 4 mice in the two groups was anesthetized with 3.5% sevoflurane for 1 hour. Subsequently, mRNA was isolated from hippocampal cells and RNA sequencing was performed on an Illumina HiSeq 2500 platform. Mapping of the quality-controlled, filter paired-end reads to mouse genomes and quantification of the expression level of each gene were performed using R software. Results: The Lhx9 gene, which is thought to be associated with neuronal inflammation, was the most highly upregulated gene in aged mice. The Epyc gene, which encodes a protein related to the phospholipase-C pathway and ERK signaling, was the most down-regulated gene in aged mice. Conclusions: The findings suggest that sevoflurane anesthesia induces neuronal inflammation via a LIMhomeodomain family related gene in aged mice and causes POCD.

Effect of sevoflurane anesthesia in diabetic pregnant rats on cognitive function of offspring rats

Objective To investigate the effects of sevoflurane anesthesia in diabetic pregnant rats on the cognitive function of the offspring rats. Methods Forty female Sprague-Dawley rats and 5 male rats, weighing 200-250 g, were used in the study.Twenty pregnant rats at 7 weeks of gestation were randomly selected, and diabetes mellitus was induced by intraperitoneal streptozotocin 45 mg/kg and confirmed by blood glucose level >10.4 mmol/L.Twenty pregnant rats at 20 days of gestation, in which diabetes mellitus was not induced, were selected and divided into 2 groups(n=10 each)using a random number table: sevoflurane group(group S)and control group(group C). Twenty pregnant rats at 20 days of gestation with diabetes mellitus were selected and divided into 2 groups(n=10 each) using a random number table: sevoflurane group(group DS)and control group(group DC). In DS and S groups, the pregnant rats were placed in a self-made anesthetic box and inhaled 2% sevoflurane for 2 h. At 6 weeks after birth, the offspring rats were selected, and Morris water maze test was performed.The rats were sacrificed, brains were removed, and the hippocampi and cortex were removed for determination of phosphorylated cyclic adenosine monophosphate response element-binding protein(p-CREB)expression using immuno-histochemistry. Results Compared with group C, the escape latency was significantly prolonged, and the frequency of crossing the original platform was significantly decreased in S and DC groups(P<0.05). Compared with group DC, the escape latency was significantly prolonged, and the frequency of crossing the original platform was significantly decreased in group DS(P<0.01). Compared with group S, the escape latency was significantly prolonged, the frequency of crossing the original platform was significantly decreased(P<0.05), and lighter staining for p-CREB was found, and the number of p-CREB positive cells was decreased in the hippocampus and cortex in group DS. Conclusion Sevoflurane anesthesia-induced cognitive dysfunction is aggravated in the offspring rats of diabetic pregnant rats, and the mechanism is related to inhibition of CREB phosphorylation. Key words: Anesthetics, inhalation; Diabetes mellitus; Cognition disorders; Pregnant