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Elderly individuals undergoing surgical procedures are often confronted with the peril of experiencing postoperative cognitive dysfunction (POCD). Prior research has demonstrated the exacerbating effect of sevoflurane anesthesia on neuroinflammation, which can further deteriorate the condition of POCD in elderly patients. Intermittent fasting (IF) restricts food consumption to a specific time window and has been demonstrated to ameliorate cognitive dysfunction induced by neuropathic inflammation. We subjected 18-month-old male mice to 16 hours of fasting and 8 hours of unrestricted eating over a 24-hour period for 0, 1, 2, and 4 weeks, followed by abdominal exploration under sevoflurane anesthesia. In this study, we aim to explore the potential impact of IF on postoperative cognitive function in aged mice undergoing sevoflurane surgery through the preoperative implementation of IF measures. The findings indicate two weeks of IF leads to a significant enhancement of learning and memory capabilities in mice following surgery. The cognitive performance, as determined by the novel object recognition and Morris water maze tests, as well as the synaptic plasticity, as measured by in vivo electrophysiological recordings, has demonstrated marked improvements. Furthermore, the administration of IF markedly enhances the expression of synaptic-associated proteins in hippocampal neurons, concomitant with a decreasing expression of pro-inflammatory factors and a reduced density of microglial cells within the hippocampal brain region. To summarize, the results of this study indicate that IF may mitigate inflammation in the hippocampal area of the brain. Furthermore, IF appears to provide a safeguard against cognitive impairment and synaptic plasticity impairment brought on by sevoflurane anesthesia., Competing Interests: Declaration of Competing Interest The authors assert that the study was carried out without any commercial or financial affiliations that could be interpreted as a possible conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Sevoflurane is a widely used obstetric general anesthetic, but the neurotoxic effects of late-pregnancy exposure to one minimum alveolar concentration ([MAC], 2.5%) of sevoflurane on offspring remain unclear. We investigated whether exposure to 2.5% sevoflurane during late pregnancy would affect offspring hippocampal neuronal development and neurocognitive function. On gestational day 18 (G18), rats were randomly treated with 2.5% sevoflurane in 50% oxygen for 1 (Sev × 1), 3 (Sev × 3), or 6 h (Sev × 6). The neuronal apoptosis rate and mature brain-derived neurotrophic factor (mBDNF) and postsynaptic density protein 95 (PSD-95) expression levels were measured in offspring hippocampi on postnatal day 1 (P1) and P35. Dendritic spine formation and cognitive function were examined on P35. The neuronal apoptosis rate was enhanced, and mBDNF and PSD-95 levels were reduced in the Sev × 3 and Sev × 6 groups on P1. mBDNF and PSD-95 levels were also decreased in the Sev × 6 group on P35. The error rate was elevated in the maze test, whereas dendritic spine density and long-term potentiation (LTP) were reduced in the Sev × 6 group on P35. To determine whether exposure to an enriched environment (EE) would ameliorate sevoflurane's neurotoxic effects, offspring from another Sev × 6 group were exposed to either a standard environment (SE) or an EE. Lower error rates and greater dendritic spine densities and LTP were found in the Sev × 6 + EE vs. Sev × 6 + SE group. Collectively, we showed that exposing rats to 1 MAC sevoflurane for 3 h during late pregnancy increased neuronal apoptosis in neonates but did not impair neuronal development or cognitive function in juvenile rats, whereas a 6-h exposure impaired neuronal development and cognitive function in juvenile rats, effects that were attenuated by an EE.

Background: Cerebral ischemia–hypoxia leads to excitotoxicity‐mediated neuronal damage and cognitive dysfunction, especially in the elderly. Excessive intracellular [Cl−]i accumulation weakens γ‐aminobutyric acid (GABA) compensatory effects. Sub‐anesthetic dose of propofol protected the brain against ischemia–hypoxia, which was abolished by blocking Cl− efflux transporter K+/Cl− cotransporter 2 (KCC2). We aimed to determine whether low‐dose anesthetic combined with [Cl−]i regulators could restore the compensatory GABAergic system and improve cognitive function. Methods: Chronic cerebral hypoxia (CCH) model was established by bilateral carotid artery ligation in aged rats. Sub‐dose of anesthetics (propofol and sevoflurane) with or without KCC2 agonist N‐ethylmaleimide (NEM) or Na+/K+/Cl− cotransporter 1 (NKCC1) antagonist bumetanide (BTN) was administered systemically 30 days post‐surgery. Primary rat hippocampal neuronal cultures were subjected to hypoxic injury with or without drug treatment. Memory function, hippocampal neuronal survival, GABAergic system functioning, and brain‐derived neurotrophic factor (BDNF) expressions were evaluated. Results: Sub‐anesthetic dose of combined propofol (1.2 μg mL−1) and sevoflurane [0.7 MAC (minimum alveolar concentration)] did not aggravate the hypoxic brain injury in rats or cell damage in neuronal cultures. Adding either BTN or NEM protected against hypoxic injury, associated with improved cognitive function in vivo, less intracellular accumulation of [Cl−]i, reduced cell death, restored GABAergic compensation, and increased BDNF expression both in vivo and in vitro. Conclusion: Sub‐anesthetic dose of propofol and sevoflurane is a recommended anesthesia regimen in at‐risk patients. Restoration of [Cl−]i homeostasis and GABAergic could further reduce the brain damage caused by ischemia–hypoxia. [ABSTRACT FROM AUTHOR]

Purpose: Animal studies have demonstrated that propofol post-conditioning produces long-term neuroprotection in focal cerebral ischemia-reperfusion injury. However, whether propofol post-conditioning provides neuroprotection in human beings has never been explored. The aim of this study was to evaluate the role of propofol post-conditioning on oxidative stress and post-operative cognitive function following aneurysm clipping. Materials and Methods: Sixty patients undergoing intracranial aneurysm clipping were randomized into a propofol post-conditioning group or a sevoflurane group. Sevoflurane (0.5-2%) was used for maintenance anesthesia in both groups. In the propofol post-conditioning group, the inhaled concentration of sevoflurane was reduced after temporary clip removal to keep the bispectral index (BIS) value between 40 and 60, and propofol (Cp 1.2 µg/mL) was subsequently started. Blood samples were drawn at six time points: before induction, immediately after clip removal, at the end of the operation, 24-h post-surgery, 3 days post-surgery, and 7 days post-surgery. Oxidative stress and cognitive function were measured. Results: Between the conclusion of the operation to 7 days after surgery, propofol post-conditioning decreased the serum concentration of •OH and 8-isoprostane and increased γ-tocopherol and SOD. Reduced micronuclei and nucleoplasmic bridges were observed in the propofol post-conditioning group. Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores were improved by propofol post-conditioning compared to the group that received no propofol. Conclusions: Together, our data suggest that propofol post-conditioning (Cp 1.2 µg/mL) may protect the brain from oxidative stress injury up to 7 days post-surgery after temporary parent artery clipping. Furthermore, the neuroprotection induced by propofol post-conditioning may contribute to improvement in cognitive function. [ABSTRACT FROM AUTHOR]

Postoperative cognitive decline ( POCD) is a common geriatric complication, and sevoflurane is a widely accepted inducer of POCD. Although the aetiology of POCD is not clear, a breach in the blood-brain barrier ( BBB) is involved in early POCD. Annexin A1 has shown protective effects on BBB function. The objective of this study was to investigate both the effects of sevoflurane on the components of the BBB and the underlying mechanism. In vivo treatment with 3.6% sevoflurane for 6 h disrupted BBB components led to fibrinogen invasion and down-regulation of Annexin A1 expression at 24 h after inhalation. The administration of human recombinant Annexin A1 (hr Annexin A1) attenuated the disruption of BBB components, thereby reducing fibrinogen invasion. In addition, the administration of hr Annexin A1 improved cognitive function after the inhalation of 3.6% sevoflurane for 6 h. Moreover, in cultured endothelial cells, 3.6% sevoflurane for 6 h increased GSK-3β and decreased β-catenin levels at 24 h after inhalation. The activation/inhibition of the Wnt/β-catenin signalling pathway attenuated/worsened the sevoflurane-induced decrease in Annexin A1. Our findings indicate that in endothelial cells, treatment with 3.6% sevoflurane for 6 h inhibits the Wnt/β-catenin signalling pathway, thereby increasing GSK-3β and decreasing β-catenin. By inhibiting this pathway, the gas anaesthetic sevoflurane down-regulated Annexin A1, which consequently breached the BBB and induced POCD. [ABSTRACT FROM AUTHOR]

The objective of this article is to evaluate the effect of dexmedetomidine on emergence agitation (EA) and recovery profiles in children after sevoflurane anesthesia and its pharmacological mechanisms. Standard bibliographic databases, including MEDLINE, EMBASE, PsycINFP, Springer and ISI Web of Knowledge, were artificially searched to identify all randomized controlled trials (RCTs) comparing the impact of dexmedetomidine with placebo, fentanyl and midazolam on EA and recovery profiles after sevoflurane anesthesia in post-anesthesia care unit (PACU). Two authors assessed the quality of each study independently in accordance with strict inclusion criteria and extracted data. RevMan 5.0 software was applied for performing statistic analysis. The outcomes analyzed included: 1) incidence of EA, 2) emergence time, 3) time to extubation, 4) incidence of post-operation nausea and vomiting, 5) number of patients requiring an analgesic, and 6) time to discharge from PACU. A total of 1364 patients (696 in the dexmedetomidine group and 668 in the placebo, fentanyl and midazolam group) from 20 prospective RCTs were included in the meta-analysis. Compared with placebo, dexmedetomidine decreased the incidence of EA (risk ratio [RR] 0.37; 95% CI 0.30 to 0.46), incidence of nausea and vomiting (RR 0.57; 95% CI 0.38 to 0.85) and number of patients requiring an analgesic (RR 0.43; 95% CI 0.31 to 0.59). However, dexmedetomidine had a significantly delayed effect on the emergence time (weighted mean differences [WMD] 1.16; 95% CI 0.72 to 1.60), time to extubation (WMD 0.61; 95% CI 0.27 to 0.95), and time to discharge from recovery room (WMD 2.67; 95% CI 0.95 to 4.39). Compared with fentanyl (RR 1.39; 95% CI 0.78 to 2.48) and midazolam (RR 1.12; 95% CI 0.54 to 2.35), dexmedetomidine has no significantly difference on the incidence of EA. However, the analgesia effect of dexmedetomidine on postoperation pain has no significantly statistical differences compared with fentanyl (RR 1.12; 95% CI 0.66 to 1.91), which implied that its analgesia effect might play an important role in decreasing the incident of EA. No evidence of publication bias was observed. [ABSTRACT FROM AUTHOR]

Abstract: The underlying causes of postoperative cognitive decline (POCD) in old patients remained unelucidated, and there are little descriptions on mechanisms associated with the blood–brain barrier (BBB) disruption during POCD. We therefore tested the effects of orthopedic surgery with different concentrations of sevoflurane for 2h on the behavior test and the BBB permeability in aged rats. 18-month rats were divided into control group and surgical group with propofol anesthesia (0.7mgkg−1 min−1) and 1.0MAC, 1.3MAC, and 1.5MAC sevoflurane inhalation for 2h. We assessed their cognitive function via Y-maze and fear conditioning test on day 1, 3, and 7 after experiments. Animals were then assigned to control group, propofol (2h, 0.7mgkg−1 min−1) group, surgery plus propofol group and surgery plus 1.5MAC sevoflurane inhalation for 2h. Their hippocampal BBB permeability was detected with Evans blue quantification. Alterations of tight junctions in hippocampus were measured with occludin and claudin-5 western blot. Then we assessed matrix metalloproteinase-2,9 (MMP-2,9) via western blot and immunohistochemistry staining at day 1, 3, 7, and 14 after experiments. Surgery impaired cognitive function and increased Evans blue leakage into the hippocampus in aged rats while 2h of 1.5MAC sevoflurane inhalation potentiated these effects. Surgery induced occludin protein expression decreases and MMP-2,9 proteins increase and these influences can be enhanced by high concentration of sevoflurane inhalation. In conclusion, 1.5MAC sevoflurane for 2h exacerbated cognitive impairment induced by orthopedic surgery in aged rats and the breach in BBB may be involved in this process. [Copyright &y& Elsevier]

Background We revealed that a high concentration of sevoflurane exacerbated cognitive impairment in aged rats, and the inhibition of GluA2 subunit internalization facilitated neuroprotection after a cerebral ischemic injury. However, the trafficking of GluA2 in POCD and its underlying mechanism are not clear. We thus detected the effects of sevoflurane for different inhalation durations on postoperative cognitive function and investigated the role of GluA2 subunit trafficking in this process. Methods A rat model of orthopedic surgery was performed with different durations of 1.5 MAC sevoflurane inhalation. Cognitive function was evaluated by manipulating the Y maze and fear conditioning tests for 7 days after experiments. Western blot, ELISA and coimmunoprecipitation were applied to analyze GluA2 internalization, PI3K expression and its activity, as well as alterations to the MEF2-Arc pathway in the hippocampus. Neuron apoptosis and the spine morphology in the hippocampus were also observed. Results We found that neuron apoptosis and GluA2 internalization increased following surgery and 1.5 MAC sevoflurane inhalation for 2 h, possibly due to the decrease of the PI3K-GluA2 complex and PI3K activity in the hippocampus after prolonged 1.5 MAC sevoflurane inhalation. We also observed that the MEF2-Arc pathway contributed to long-term cognitive function, which also impaired the spinal morphology after 1.5 MAC sevoflurane inhalation for 2 h. Conclusion The above results suggest that 1.5 MAC sevoflurane inhalation for 2 h potentiated surgery-impaired cognitive function and that the inhibition of PI3K-AMPAR GluA2 as well as activation of the MEF2-Arc signal pathway contributes to different stages of POCD. [ABSTRACT FROM AUTHOR]