Restoration Algorithm-Based Ultrasound Image in Evaluating the Effect of Dexmedetomidine on Patients with Neurological Disorder Anesthetized by Sevoflurane.

The study focused on the application value of ultrasound images processed by restoration algorithm in evaluating the effect of dexmedetomidine in preventing neurological disorder in patients undergoing sevoflurane anesthesia. 90 patients undergoing tonsillectomy anesthesia were randomly divided into normal saline group, propofol group, and dexmedetomidine group. The ultrasound images were processed by restoration algorithm, and during the postoperative recovery period, ultrasound images were used to evaluate. The results showed that the original ultrasonic image was fuzzy and contained interference noise, and that the image optimized by restoration algorithm was clear, without excess noise, and the image quality was significantly improved. In the dexmedetomidine group, the extubation time was 10.6 ± 2.3 minutes, the recovery time was 8.4 ± 2.2 minutes, the average pain score during the recovery period was 2.6 ± 0.7, and the average agitation score was 7.2 ± 2.4. Of 30 patients, there were 13 cases with vertigo and 1 case with nausea and vomiting. The vascular ultrasound imaging showed that, in the dexmedetomidine group, the peak systolic velocities (PSV) of the bilateral vertebral arteries during the recovery period were 67.7 ± 14.3 and 67.9 ± 15.2 cm/s, respectively; the end-diastolic velocities (EDV) of the bilateral vertebral arteries were 27.8 ± 6.7 and 24.69 ± 5.9 cm/s, respectively; the PSV in bilateral internal carotid artery systolic peak velocities were 67.2 ± 13.9 and 67.8 ± 12.7 cm/s, respectively; the EDV in bilateral internal carotid arteries were 27.7 ± 5.3 and 26.9 ± 4.9 cm/s, respectively; bilateral vertebral artery resistance indexes (RIs) were 0.6 ± 0.02 and 0.71 ± 0.08, respectively; the bilateral internal carotid artery RIs were 0.57 ± 0.04 and 0.58 ± 0.06, respectively, all better than the normal saline group (12.1 ± 2.5 minutes, 10.1 ± 2.3 minutes, 3.9 ± 0.6, 10.6 ± 3.7, 15 cases, 11 cases, 81.5 ± 13.6, 80.7 ± 11.6 cm/s, 29.3 ± 6.8, 28.9 ± 6.7 cm/s, 74.3 ± 10.2, 73.9 ± 12.5 cm/s, 29.1 ± 4.3, 29 ± 4.5 cm/s, 0.84 ± 0.06, 0.83 ± 0.05, 0.8 ± 0.04, and 0.81 ± 0.05) and the propofol group (11.4 ± 2.1 minutes, 9.0 ± 2.1 minutes, 3.4 ± 0.8, 8.5 ± 2.3, 12 cases, 9 cases, 72.5 ± 12.9, 73.4 ± 11.8 cm/s, 28.6 ± 5.4, 26.5 ± 5.1 cm/s, 72.1 ± 11.4, 73.5 ± 10.6 cm/s, 28.8 ± 5.6, 27.3 ± 4.7 cm/s, 0.78 ± 0.07, 0.82 ± 0.06, 0.76 ± 0.03, and 0.78 ± 0.05), and the differences were statistically significant (P < 0.05). In conclusion, ultrasound images processed by restoration algorithm have high image quality and high resolution. The dexmedetomidine can prevent neurological disorder in patients with sevoflurane anesthesia and is suggested in postoperative rehabilitation.

General anesthesia activates the mitochondrial unfolded protein response and induces age-dependent, long-lasting changes in mitochondrial function in the developing brain.

General anesthesia induces changes in dendritic spine number and synaptic transmission in developing mice. These changes are rather disturbing, as similar changes are seen in animal models of neurodevelopmental disorders. We previously suggested that mTor-dependent upregulation of mitochondrial function may be involved in such changes. To further understand the significance of mitochondrial changes after general anesthesia during neurodevelopment, we exposed young mice to 2.5 % sevoflurane for 2 h followed by injection of rotenone, a mitochondrial complex I inhibitor. In postnatal day 17 (PND17) mice, intraperitoneal injection of rotenone not only blocked sevoflurane-induced increases in mitochondrial function, it also prevented sevoflurane-induced changes in excitatory synaptic transmission. Interestingly, similar changes were not observed in younger, neonatal mice (PND7). We next assessed whether the mitochondrial unfolded protein response (UPRmt) acted as a link between anesthetic exposure and mitochondrial function. Expression of UPRmt proteins, which help maintain protein-folding homeostasis and increase mitochondrial function, was increased 6 h after sevoflurane exposure. Our results show that a single, brief sevoflurane exposure induces age-dependent changes in mitochondrial function that constitute an important mechanism for the increase in excitatory synaptic transmission in late postnatal mice, and also suggest mitochondria and UPRmt as potential targets for preventing anesthesia toxicity.

Sevoflurane depresses neurons in the medial parabrachial nucleus by potentiating postsynaptic GABAA receptors and background potassium channels.

Despite persistent clinical use for over 170 years, the neuronal mechanisms by which general anesthetics produce hypnosis remain unclear. Previous studies suggest that anesthetics exert hypnotic effects by acting on endogenous arousal circuits. Recently, it has been shown that the medial parabrachial nucleus (MPB) is a novel wake-promoting component in the dorsolateral pons. However, it is not known whether and how the MPB contributes to anesthetic-induced hypnosis. Here, we investigated the action of sevoflurane, a widely used volatile anesthetic agent that best represents the drug class of halogenated ethers, on MPB neurons in mice. Using in vivo fiber photometry, we found that the population activities of MPB neurons were inhibited during sevoflurane-induced loss of consciousness. Using in vitro whole-cell patch-clamp recordings, we revealed that sevoflurane suppressed the firing rate of MPB neurons in concentration-dependent and reversible manners. At a concentration equal to MAC of hypnosis, sevoflurane potentiated synaptic GABAA receptors (GABAA-Rs), and the inhibitory effect of sevoflurane on the firing rate of MPB neurons was completely abolished by picrotoxin, which is a selective GABAA-R antagonist. At a concentration equivalent to MAC of immobility, sevoflurane directly hyperpolarized MPB neurons and induced a significant decrease in membrane input resistance by increasing a basal potassium conductance. Moreover, pharmacological blockade of GABAA-Rs in the MPB prolongs induction and shortens emergence under sevoflurane inhalation at MAC of hypnosis. These results indicate that sevoflurane inhibits MPB neurons through postsynaptic GABAA-Rs and background potassium channels, which contributes to sevoflurane-induced hypnosis.

Neuroprotective effect of CTRP3 overexpression against sevoflurane anesthesia-induced cognitive dysfunction in aged rats through activating AMPK/SIRT1 and PI3K/AKT signaling pathways.

OBJECTIVE: To investigate the effects of C1q/tumor necrosis factor-related protein-3 (CTRP3) on postoperative cognitive dysfunction (POCD) and elucidate the potential regulatory mechanism in sevoflurane anesthesia-induced aged rats. MATERIALS AND METHODS: A sevoflurane anesthesia-induced POCD aged rat model was established and hematoxylin and eosin (H&E) staining was used to detect pathological changes of hippocampal neurons. Morris water maze task test was performed to determine the learning and memory ability of rats. Immunofluorescence, quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot were used to detect CTRP3 expression. Enzyme-linked immunosorbent assay (ELISA) or qRT-PCR assays were used to evaluate the changes of markers of brain damage and inflammatory cytokines. Terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) assay was used to assess the apoptosis of nerve cells in hippocampus. Western blot assay were used to measure the expression levels of apoptosis-related protein, and AMP-activated protein kinase (AMPK)/SIRT1 and PI3K/AKT pathway. RESULTS: Sevoflurane exposure led to brain injury, cognitive dysfunction in aged rats and decreased the expression of CTRP3. Overexpression of CTRP3 could suppress nerve cell apoptosis, inhibit neuronal inflammation, reduce brain tissue damage and improve cognitive dysfunction of aged rats after sevoflurane anesthesia. Further studies showed that CTRP3 may play a role in POCD by regulating AMPK/SIRT1 and PI3K/AKT signaling pathways. CONCLUSIONS: CTRP3 may effectively protect against sevoflurane-induced cognitive dysfunction and served as a potential predictive indicator and therapy target for POCD.

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

AIMS: Anaesthesia-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 METHODS: Hippocampi 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 FINDINGS: Sevoflurane 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. SIGNIFICANCE: Our 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.

Volatile anesthetic sevoflurane pretreatment alleviates hypoxia-induced potentiation of excitatory inputs to striatal medium spiny neurons of mice.

Sevoflurane, a commonly used anesthetic in surgery, has drawn attention because of its preconditioning effects in hypoxic conditions. To investigate the preconditioning effects in the striatum, a common site for ischemic stroke, we collected whole-cell current-clamp recordings from striatal medium spiny neurons. In our in vitro brain slice experiments, deprivation of oxygen and glucose depolarized the striatal neurons to subthreshold potentials, and the pre-administration of sevoflurane (4%, 15 min) prolonged the time to depolarization. Furthermore, transient hypoxia induced the potentiation of excitatory postsynaptic potentials, which play a part in post-ischemic excitotoxicity. Glibenclamide, a KATP channel inhibitor, reversed the prolonged time to depolarization and the prevention of the pathological potentiation of excitatory responses, indicating that the short exposure to sevoflurane likely participates in neuroprotection against hypoxia via activation of KATP channels. A monocarboxylate transporter blocker, 4-CIN, also depolarized striatal neurons. Interestingly, the blockade of monocarboxylate transporters that supply lactate to neurons caused the pathological potentiation, even in the presence of enough oxygen and glucose. In this case, sevoflurane could not prevent the pathological potentiation, suggesting the involvement of monocarboxylate transporters in the sevoflurane-mediated effects. These results indicate that sevoflurane protects striatal neurons from hypoxic damage and alleviates the pathological potentiation. Under these conditions, sevoflurane may become an effective intervention for patients undergoing surgery.

Neonatal exposure to sevoflurane caused cognitive deficits by dysregulating SK2 channels and GluA2-lacking AMPA receptors in juvenile rat hippocampus.

Anesthetics exposure to neonates leads to impairment of hippocampal synaptic plasticity and cognitive functions later in life. This phenomenon complies with the concept of metaplasticity: a priming stimulation can affect induction of synaptic plasticity mins or days later. We aimed to understand whether small conductance Ca2+-activated potassium channel type2 (SK2) and subunit composition of AMPA receptors are altered and contribute to sevoflurane-induced metaplasticity. To fulfill this goal, we exposed neonatal rats (postnatal day 7) to 2% sevoflurane for 2 h (sevoflurane rats) and examined synaptic plasticity in the hippocampus and cognitive function in juvenile rats (postnatal day 30-35). We observed that the juvenile sevoflurane rats showed elevation in the threshold for LTP induction, facilitation of LTD induction, and cognitive dysfunctions. Meanwhile, these rats also exhibited increased surface expression of SK2 and enhanced synaptic recruitment of GluA2-lacking AMPA receptors, which possess stronger inward rectification. Blocking SK2 eliminated inward rectification of AMPA receptors in juvenile sevoflurane rats. Interestingly, blocking either SK2 channels or GluA2-lacking AMPA receptors normalized LTP, LTD, and spatial memory in juvenile sevoflurane rats. Our data indicate that neonatal sevoflurane anesthesia have negative impact on cognitive function extended to juvenile rats probably through increasing surface expression of SK2 and synaptic recruitment of GluA2-lacking AMPA receptors. This study provides a new sight for sevoflurane induced metaplasticity.

Sevoflurane-induced isoelectric EEG and burst suppression: differential and antagonistic effect of added nitrous oxide.

The objective of this study was to investigate whether nitrous oxide influenced the ED50 of sevoflurane for induction of isoelectric electroencephalogram (ED50isoelectric ) differently from its influence on the ED50 of sevoflurane for electroencephalogram burst suppression (ED50burst ). In a prospective, randomised, double-blind, parallel group, up-down sequential allocation study, 77 ASA physical status 1 and 2 patients received sevoflurane induction and, after tracheal intubation, were randomly allocated to receive sevoflurane with either 40% oxygen in air (control group) or 60% nitrous oxide in oxygen mixture (nitrous group). The ED50isoelectric in the two groups was determined using Dixon's up and down method, starting at 2.5% with 0.2% step size of end-tidal sevoflurane. The electroencephalogram was considered as isoelectric when a burst suppression ratio of 100% lasted > 1 min. The subsequent concentrations of sevoflurane administered were determined by the presence or absence of isoelectric electroencephalogram in the previous patient in the same group. The ED50isoelectric in the nitrous group 4.08 (95%CI, 3.95-4.38)% was significantly higher than that in the control group 3.68 (95%CI, 3.50-3.78)% (p < 0.0001). The values for ED50burst were 3.05 (95%CI, 2.66-3.90)% and 3.02 (95%CI, 3.00-3.05)% in nitrous group and control group, respectively (p = 0.52). The addition of 60% nitrous oxide increases ED50isoelectric , but not the ED50burst of sevoflurane. Neither result indicates an additive effect of anaesthetic agents, as might be expected, and possible reasons for this are discussed.