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In this work, two series of water-soluble derivatives were designed and synthesized based on the structure of propofol as the lead compound. Furthermore, the anesthetic activities of the synthesized compounds were evaluated in vivo against mice, and the in vitro propofol release rate from five target compounds was determined. The findings of this study have shown that series II compounds which possess the structure feature of propofol + γ-hydroxybutyric acid + α-aminoacetate or γ-aminobutyrate have higher therapeutic index than that of series I compounds which possess the structure feature of propofol + α-aminoacetate or β-aminopropionate. In addition, the rate of propofol released from series II compounds was significantly better than that of series I compounds. Among series II compounds, compound II-20 had a therapeutic index of 5.6 (propofol = 2.7), a duration time of 571 s (propofol = 57 s), and no significant toxicity was observed in vivo, which made it valuable for further development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: This study aimed to compare the impact of remimazolam-based versus propofol-based intravenous anesthesia on surgical stress and post-operative immune function in patients undergoing gastric radical surgery., Patients and Methods: Sixty-eight patients aged 50 to 80 undergoing gastric radical surgery were randomly assigned to the remimazolam group (group R) or the propofol group (group P), receiving remimazolam or propofol-based intravenous anesthesia, respectively. The primary outcome measured was peri-operative serum stress indicators and lymphocyte subtypes. Secondary outcomes included hemodynamic vitals, recovery quality, postoperative pain profiles and potential adverse effects., Results: The demographic and surgical characteristics of the 60 analyzed patients were comparable. The absolute counts of CD3+CD4+ and CD3+CD8+ cell decreased significantly on POD1 compared with baseline. On POD3, the numbers of CD3+CD4+ cells in group R were lower than baseline and Group P, whereas the CD3+CD8+ cell counts in both groups were lower than baseline, with group R higher than group P. The CD3-CD16+CD56+ cell numbers in both groups on POD1 and POD3 decreased significantly compared to baseline with group P lower than group R on POD3. The serum levels of IL-1β, IL-6, TNF-α, ACTH and COR rose sharply 2 hours after the beginning of surgery compared to baseline. Notably, all these parameters in group R were higher than those in group P. Additionally, blood pressure and intra-operative vasoactive drug frequency in group R were higher than that in group P. No significant differences in recovery quality, postoperative pain profiles, and potential adverse effects were observed., Conclusion: Remimazolam-based intravenous anesthesia might favour the recovery of cellular immune function in early postoperative period compared to propofol. On the contrary, remimazolam was inferior to propofol in suppressing surgical stress. Further studies with larger sample sizes are needed to confirm our findings., Competing Interests: The authors declare that they have no conflicts of interest in this work., (© 2024 Xu et al.)

Objectives: Several anaesthetic protocols for caesarean section (c-section) have been described in dogs; however, anaesthesiological studies in cats undergoing c-section are lacking. The aim of this study was to assess the viability and outcome of kittens born from queens undergoing emergency c-section and receiving propofol or alfaxalone for anaesthetic induction and isoflurane for maintenance of general anaesthesia., Methods: All cats admitted to the Veterinary Teaching Hospital of the University of Bologna between January 2014 and December 2022 for dystocia that had undergone an emergency c-section were analysed in this retrospective study. The queens received propofol 2-6 mg/kg IV (group P) or alfaxalone 1-3 mg/kg IV (group A) administered slowly; general anaesthesia was maintained with isoflurane. Survival of all the kittens was evaluated at birth and after 24 h; in addition, heart rate, respiratory rate and mucous membrane colour were evaluated in the kittens at birth., Results: Of the 14 cats included in the study, eight received alfaxalone (group A) and six received propofol (group P) for induction of the general anaesthesia. A total of 50 kittens were born by c-section: 30 kittens in group A and 20 in group P. The overall survival of the kittens was 90% at birth: 96.7% (29/30) for group A and 80% (16/20) for group P. The 24 h survival rate was 93.1% for group A and 87.5% for group P., Conclusions and Relevance: The results of the present study demonstrated that in cats undergoing c-section, both alfaxalone and propofol are feasible for the induction of general anaesthesia., Competing Interests: Conflict of interestThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Subarachnoid hemorrhage (SAH) is associated with neurocognitive impairment. Recent data suggest that sevoflurane attenuates edema formation after SAH in rats. However, so far, no information is available about the long-term repair phase, nor if sevoflurane impacts functionality by increasing vascularity. This study tested whether sevoflurane postconditioning would improve long-term neurologic deficit through increased formation of new vessels close to the hemorrhage area., Methods: Fifty-three animals were subjected to SAH or sham surgery with or without a 2-hour sevoflurane postconditioning (versus propofol anesthesia). Animal survival, including dropout animals due to death or reaching termination criteria, as well as neurologic deficit, defined by the Garcia score, were assessed 2 hours after recovery until postoperative day 14. On day 14, blood samples and brain tissue were harvested. Vessel density was determined by the number of cluster of differentiation 31 (CD31)-positive vessels, and activated glial cells by glial fibrillary acidic protein (GFAP)-positive astrocytes per field of view., Results: The survival rate for sham animals was 100%, 69% in the SAH-propofol and 92% in the SAH-sevoflurane groups. According to the log-rank Mantel-Cox test, survival curves were significantly different ( P = .024). The short-term neurologic deficit was higher in SAH-propofol versus SAH-sevoflurane animals 2 hours after recovery and on postoperative day 1 (propofol versus sevoflurane: 14. 6 ± 3.4 vs 15. 9 ± 2.7 points, P = .034, and 16. 2 ± 3.5 vs 17. 8 ± 0.9 points, P = .015). Overall complete recovery from neurologic deficit was observed on day 7 in both SAH groups (18. 0 ± 0.0 vs 18. 0 ± 0.0 points, P = 1.000). Cortical vascular density increased to 80. 6 ± 15.0 vessels per field of view in SAH-propofol animals (vs 71. 4 ± 10.1 in SAH-sevoflurane, P < .001). Activation of glial cells, an indicator of neuroinflammation, was assessed by GFAP-positive astrocytes GFAP per field of view. Hippocampal GFAP-positive cells were 201 ± 68 vs 179 ± 84 cells per field of view in SAH-propofol versus SAH-sevoflurane animals ( P < .001)., Conclusions: Sevoflurane postconditioning improves survival by 23% (SAH-sevoflurane versus SAH-propofol). The sevoflurane intervention could attenuate the early neurologic deficit, while the long-term outcome was similar across the groups. A higher vascular density close to the SAH area in the propofol group was not associated with improved outcomes., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2024 International Anesthesia Research Society.)

Breast cancer is the most prevalent cancer among women worldwide, characterized by a high mortality rate and propensity for metastasis. Although surgery is the standard treatment for breast cancer, there is still no effective method to inhibit tumor metastasis and improve the prognosis of patients with breast cancer after surgery. Propofol, one of the most widely used intravenous anesthetics in surgery, has exhibited a positive association with improved survival outcomes in patients with breast cancer post‑surgery. However, the underlying molecular mechanism remains to be elucidated. The present study revealed that triple negative breast cancer cells, MDA‑MB‑231 and 4T1, exposed to propofol exhibited a significant decrease in cell viability. Notably, propofol exhibited minimal cytotoxic effects on HUVECs under the same conditions. Furthermore, propofol significantly inhibited the migration and invasion ability of MDA‑MB‑231 and 4T1 cells. Propofol promoted apoptosis in 4T1 cells through upregulation of Bax and cleaved caspase 3, while downregulating B‑cell lymphoma‑extra large. Concomitantly, propofol induced cell cycle arrest of 4T1 cells by downregulating cyclin E2 and phosphorylated cell division cycle 6. Furthermore, propofol exhibited excellent anticancer efficacy in a 4T1 breast cancer allograft mouse model. The present study sheds light on the potential of propofol as an old medicine with a novel use for breast cancer treatment.

Propofol has become a microtubule-stabilizing drug for prostate cancer (PC) therapy, but propofol resistance impairs the therapeutic effect. This study aimed to explore the regulatory mechanism of propofol in the pathogenesis of PC through mechanisms involving N6-methyladenosine (m6A) modification. The changes in PC cell malignancy were evaluated by means of transwell, cell counting kit 8 (CCK-8), western blotting and tumour xenograft model assays. Long noncoding RNA TRHDE-AS1 and m6A methyltransferase METTL14 expression levels were determined via reverse transcription quantitative polymerase chain reaction (RT-qPCR). The m6A modification of TRHDE-AS1 which was mediated by METTL14 was confirmed by conducting methylated RNA immunoprecipitation (MeRIP) assay. We observed that propofol (200 μM) inhibited PC cell malignancy in vivo and in vitro, elucidating that it impaired cell proliferation, migration and tumour growth but induced apoptosis. TRHDE-AS1 expression was observed to be lower in PC cells and tissues, and propofol induced TRHDE-AS1 upregulation in PC cells. Propofol was capable of reversing the tumour-promoting effect of TRHDE-AS1 knockdown in PC cells. Additionally, METTL14 was upstream of TRHDE-AS1 to induce m6A modification of TRHDE-AS1 in PC cells. Collectively, our results show that propofol prevents PC progression by upregulating TRHDE-AS1 expression and METTL14 is involved in the m6A modification of TRHDE-AS1. These findings suggest that TRHDE-AS1 may be a potential therapeutic target for the improvement of propofol's therapeutic effect., (© 2024 John Wiley & Sons Australia, Ltd.)

Background: In the neurological examination, it is crucial to identify the possible location of the lesion in order to determine the appropriate treatment process. In aggressive animals, chemical restraint may be necessary due to their non-cooperative behaviour. However, sedatives may distort the results of examinations. Therefore, a drug should be found that has minimal impact on the examination results., Objectives: To investigate the effects of acepromazine, xylazine, and propofol on spinal reflexes in healthy dogs., Methods: In a randomized, blinded study, ten native adult mixed-breed dogs were participated in three groups with a 1-week washout period between each group. Before performing each step, the spinal reflexes were evaluated. Then, in the first group, acepromazine (0.05 mg/kg, IM), in the second group, xylazine (1 mg/kg, IM), and in the third group, propofol (3 mg/kg, IV for initial bolus and 0.1 mg/kg/min for maintenance) were injected for sedation. The spinal reflexes were reevaluated at maximum sedation and at 15, 30, and 45 min thereafter., Results: Acepromazine increased the patellar reflex and decreased the panniculus reflex. Xylazine increased the cranial tibial reflex and decreased the panniculus reflex, while propofol decreased the withdrawal, and extensor carpi radialis reflexes, and suppressed the palpebral and gag reflexes., Conclusions: The drugs used in the present study did not have a significant impact on the most important reflexes evaluated in neurological examinations. Among the drugs, acepromazine has the least effects compared to other drugs, making it a suitable choice for sedation., (© 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Background: As the primary Ca 2+ release channel in skeletal muscle sarcoplasmic reticulum (SR), mutations in type 1 ryanodine receptor (RyR1) or its binding partners underlie a constellation of muscle disorders, including malignant hyperthermia (MH). In patients with MH mutations, triggering agents including halogenated volatile anaesthetics bias RyR1 to an open state resulting in uncontrolled Ca 2+ release, increased sarcomere tension, and heat production. Propofol does not trigger MH and is commonly used for patients at risk of MH. The atomic-level interactions of any anaesthetic with RyR1 are unknown., Methods: RyR1 opening was measured by [ 3 H]ryanodine binding in heavy SR vesicles (wild type) and single-channel recordings of MH mutant R615C RyR1 in planar lipid bilayers, each exposed to propofol or the photoaffinity ligand analogue m-azipropofol (AziPm). Activator-mediated wild-type RyR1 opening as a function of propofol concentration was measured by Fura-2 Ca 2+ imaging of human skeletal myotubes. AziPm binding sites, reflecting propofol binding, were identified on RyR1 using photoaffinity labelling. Propofol binding affinity to a photoadducted site was predicted using molecular dynamics (MD) simulation., Results: Both propofol and AziPm decreased RyR1 opening in planar lipid bilayers (P<0.01) and heavy SR vesicles, and inhibited activator-induced Ca 2+ release from human skeletal myotube SR. Several putative propofol binding sites on RyR1 were photoadducted by AziPm. MD simulation predicted propofol K D values of 55.8 μM and 1.4 μM in the V4828 pocket in open and closed RyR1, respectively., Conclusions: Propofol demonstrated direct binding and inhibition of RyR1 at clinically plausible concentrations, consistent with the hypothesis that propofol partially mitigates malignant hyperthermia by inhibition of induced Ca 2+ flux through RyR1., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

How consciousness is lost in states such as sleep or anesthesia remains a mystery. To gain insight into this phenomenon, concurrent recordings of electrophysiology signals in the anterior cingulate cortex and whole-brain functional magnetic resonance imaging (fMRI) are conducted in rats exposed to graded propofol, undergoing the transition from consciousness to unconsciousness. The results reveal that upon the loss of consciousness (LOC), there is a sharp increase in low-frequency power of the electrophysiological signal. Additionally, fMRI signals exhibit a cascade of deactivation across a pathway including the hippocampus, thalamus, and medial prefrontal cortex (mPFC) surrounding the moment of LOC, followed by a broader increase in brain activity across the cortex during sustained unconsciousness. Furthermore, sliding window analysis demonstrates a temporary increase in synchrony of fMRI signals across the hippocampus-thalamus-mPFC pathway preceding LOC. These data suggest that LOC may be triggered by sequential activities in the hippocampus, thalamus, and mPFC, while wide-spread activity increases in other cortical regions commonly observed during anesthesia-induced unconsciousness may be a consequence, rather than a cause of LOC. Taken together, the study identifies a cascade of neural events unfolding as the brain transitions into unconsciousness, offering insight into the systems-level neural mechanisms underpinning LOC., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: Ketamine is an intravenous anesthetic that acts as a channel blocker on the N-methyl- d -aspartate (NMDA) receptor, a glutamate receptor subtype. MK-801 is the most potent compound among noncompetitive NMDA receptor antagonists. Ketamine induces loss of the righting reflex (LORR) in rodents, which is one of the indicators of unconsciousness, whereas high doses of MK-801 produce ataxia, but not LORR. In contrast, we previously reported that MK-801 combined with a low dose of the dopamine receptor antagonist haloperidol-induced LORR in mice. To assess a neurophysiologically distinct brain state and demonstrate unconsciousness, electroencephalograms (EEG) need to be examined together with LORR. Therefore, we herein investigated EEG changes after the systemic administration of MK-801 alone or in combination with haloperidol, and compared them with those induced by ketamine, the glutamate release inhibitor riluzole, and the γ-aminobutyric acid type A receptor agonist propofol., Methods: All drugs were intraperitoneally administered to adult male ddY mice (n = 168). General anesthesia was evaluated based on the righting reflex test. Animals who exhibited no righting for more than 30 seconds were considered to have LORR. In a separate group of mice, EEG of the primary visual cortex was recorded before and after the administration of MK-801 (3.0 mg/kg) alone or in combination with haloperidol (0.2 mg/kg), ketamine (150 mg/kg), riluzole (30 mg/kg), or propofol (240 mg/kg). The waveforms recorded were analyzed using EEG power spectra and spectrograms., Results: The high dose of MK-801 alone did not induce LORR, whereas MK-801 combined with haloperidol produced LORR in a dose-dependent manner. Ketamine, riluzole, and propofol also dose-dependently induced LORR. In the EEG study, MK-801 alone induced a significant increase in δ power, while MK-801 plus haloperidol exerted similar effects on not only δ, but also θ and α power during LORR, suggesting that increases in δ, θ, and α power were necessary for LORR. The results obtained on MK-801 plus haloperidol were similar to those on ketamine in the behavioral and EEG studies, except for an increase in γ power by ketamine during LORR. Propofol significantly increased δ, θ, α, and β power during LORR. However, the EEG results obtained using riluzole, which produced a unique pattern of lower amplitude activity spanning most frequencies, markedly differed from those with the other drugs., Conclusions: This study revealed differences in EEG changes induced by various sedatives. The results obtained on MK-801 alone and MK-801 plus haloperidol suggest the importance of dopamine transmission in maintaining the righting reflex., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Anesthesia Research Society.)

Objective: To evaluate cardiopulmonary, arterial blood gas and propofol-sparing effects of magnesium sulfate (MgSO 4 ) constant rate infusion (CRI) in mechanically ventilated dogs maintained under total intravenous anesthesia with propofol., Study Design: Blinded, randomized, clinical trial., Animals: A total of 24 healthy adult dogs., Methods: Dogs were premedicated with intramuscular acepromazine (0.05 mg kg -1 ) and morphine (0.5 mg kg -1 ), followed by an intravenous (IV) bolus of saline or MgSO 4 (50 mg kg -1 over 15 minutes) and propofol (given to effect to induce anesthesia). Anesthesia was maintained with an IV propofol infusion (beginning at 0.3 mg kg -1 minute -1 , adjusted as necessary). Concurrently, one of three IV infusions were administered: GS (0.9% NaCl), GM30 (MgSO 4 , 30 mg kg -1 hour -1 ) or GM80 (MgSO 4 , 80 mg kg -1 hour -1 ). Propofol induction and maintenance doses were recorded. The following variables were recorded at baseline (T0), after bolus treatment (T1), after beginning mechanical ventilation (T5) and every 15 minutes until the end of the procedure (T15-T120): mean arterial pressure, heart rate, peripheral oxygen saturation, end-tidal partial pressure of CO 2 , temperature, blood gas variables, indirect calorimetry and extubation time. Values of p < 0.05 were considered significant., Results: Propofol induction bolus dose was lower in GM30 (31.2%, p = 0.04) and GM80 (38.9%, p = 0.003) than in GS. The maintenance propofol infusion rate in GM80 was 16.9% lower (p = 0.03), resulting in fewer propofol CRI rescues during the perioperative period. GM30 and GM80 exhibited faster extubation times than GS (46.2%, p = 0.002 and 48.9%, p = 0.001, respectively)., Conclusions and Clinical Relevance: Infusion of a 50 mg kg -1 bolus, followed by CRI of MgSO 4 (30 and 80 mg kg -1 hour -1 ), reduces the propofol induction and maintenance (CRI) requirement, maintaining cardiorespiratory stability and reducing the time required to extubation., (Copyright © 2024 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Liver cancer, one of the most common malignant tumors, has seriously threatened people's physical and mental health. The paper was conducted to investigate the functions of two different anesthesia methods on Tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) and T lymphocyte subsets in patients undergoing liver cancer resection, and to explore the liver function impact of patients undergoing liver cancer surgery. 80 liver cancer patients were split into propofol intravenous anesthesia group and sevoflurane inhalation anesthesia group. The patient's operation-related indicators and changes in TNF-α, CRP and T lymphocyte subsets before anesthesia, after anesthesia, 1 day after anesthesia, and 3 days after anesthesia were calculated. The levels of TNF-α and CRP in the two groups after operation were clearly higher than those before anesthesia, but there was no obvious difference between the two groups. After operation, the TNF-α of the propofol intravenous anesthesia group was lower than the sevoflurane inhalation anesthesia group. The CD3+, CD4+ and CD4+/CD8+ levels in both groups recovered to the pre-anaesthesia level 3 days after the operation. The levels of ALT, AST, ALB and TBIL returned to normal at d4 in both propofol intravenous anesthesia and sevoflurane inhalation anesthesia groups. Compared with evoflurane inhalation anesthesia for patients with liver cancer, intravenous anesthesia with propofol can reduce the body's inflammatory response to a certain extent, has weak inhibitory effect on T lymphocyte immune function, and a smaller effect on liver function.

Accidental awareness during general anaesthesia is a major complication. Despite the routine use of continuous electroencephalographic monitoring, accidental awareness during general anaesthesia remains relatively frequent and constitutes a significant additional cost. The prediction of patients' arousal during general anaesthesia could help preventing accidental awareness and some researchers have suggested that heart rate variability (HRV) analysis contains valuable information about the patient arousal during general anaesthesia. We conducted pilot study to investigate HRV ability to detect patient arousal. RR series and the Bispectral IndexTM (BISTM) were recorded during general anaesthesia. The pre-arousal period T0 was defined as the time at which the BISTM exceeded 60 at the end of surgery. HRV parameters were computed over several time periods before and after T0 and classified as "BISTM<60" or "BISTM≥60". A multivariate logistic regression model and a classification and regression tree algorithm were used to evaluate the HRV variables' ability to detect "BISTM≥60". All the models gave high specificity but poor sensitivity. Excluding T0 from the classification increased the sensitivity for all the models and gave AUCROC>0.7. In conclusion, we found that HRV analysis provided encouraging results to predict arousal at the end of general anaesthesia., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Julien De Jonckheere and Mathieu Jeanne are shareholders and scientific consultants for MDoloris Medical Systems. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright: © 2024 Wojtanowski et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Posttraumatic stress disorder (PTSD) is associated with glutamatergic neuron hyperactivation in the basolateral amygdala (BLA) brain area, while GABAergic interneurons in the BLA modulate glutamatergic neuron excitability. Studies have shown that propofol exerts its effects through potentiation of the inhibitory neurotransmitter γ-aminobutyric acid. The neuronal mechanism by which propofol anesthesia modulates fear memory is currently unknown. Here, we used optogenetics and chemogenetics to suppress glutamatergic neurons or activate GABAergic interneurons in the BLA to assess alterations in neuronal excitation-inhibition balance and investigate fear memory. The excitability of glutamatergic neurons in the BLA was significantly reduced by the suppression of glutamatergic neurons or activation of GABAergic interneurons, while propofol-mediated enhancement of fear memory was attenuated. We suggest that propofol anesthesia could reduce the excitability of GABAergic neurons through activation of GABAA receptors, subsequently increasing the excitability of glutamatergic neurons in the mice BLA; the effect of propofol on enhancing mice fear memory might be mediated by strengthening glutamatergic neuronal excitability and decreasing the excitability of GABAergic neurons in the BLA; neuronal excitation-inhibition imbalance in the BLA might be important in mediating the enhancement of fear memory induced by propofol., (© 2024. The Author(s).)

Consciousness requires a dynamic balance of integration and segregation in brain networks. We report an fMRI-based metric, the integration-segregation difference (ISD), which captures two key network properties: network efficiency (integration) and clustering (segregation). With this metric, we quantify brain state transitions from conscious wakefulness to unresponsiveness induced by the anesthetic propofol. The observed changes in ISD suggest a profound shift towards the segregation of brain networks during anesthesia. A common unimodal-transmodal sequence of disintegration and reintegration occurs in brain networks during, respectively, loss and return of responsiveness. Machine learning models using integration and segregation data accurately identify awake vs. unresponsive states and their transitions. Metastability (dynamic recurrence of non-equilibrium transient states) is more effectively explained by integration, while complexity (diversity of neural activity) is more closely linked with segregation. A parallel analysis of sleep states produces similar findings. Our results demonstrate that the ISD reliably indexes states of consciousness., (© 2024. The Author(s).)

Human sleep exhibits multiple, recurrent temporal regularities, ranging from circadian rhythms to sleep stage cycles and neuronal oscillations during nonrapid eye movement sleep. Moreover, recent evidence revealed a functional role of aperiodic activity, which reliably discriminates different sleep stages. Aperiodic activity is commonly defined as the spectral slope χ of the 1/frequency (1/f χ ) decay function of the electrophysiological power spectrum. However, several lines of inquiry now indicate that the aperiodic component of the power spectrum might be better characterized by a superposition of several decay processes with associated timescales. Here, we determined multiple timescales, which jointly shape aperiodic activity using human intracranial electroencephalography. Across three independent studies (47 participants, 23 female), our results reveal that aperiodic activity reliably dissociated sleep stage-dependent dynamics in a regionally specific manner. A principled approach to parametrize aperiodic activity delineated several, spatially and state-specific timescales. Lastly, we employed pharmacological modulation by means of propofol anesthesia to disentangle state-invariant timescales that may reflect physical properties of the underlying neural population from state-specific timescales that likely constitute functional interactions. Collectively, these results establish the presence of multiple intrinsic timescales that define the electrophysiological power spectrum during distinct brain states., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

Predictive coding is a fundamental function of the cortex. The predictive routing model proposes a neurophysiological implementation for predictive coding. Predictions are fed back from the deep-layer cortex via alpha/beta (8 to 30 Hz) oscillations. They inhibit the gamma (40 to 100 Hz) and spiking that feed sensory inputs forward. Unpredicted inputs arrive in circuits unprepared by alpha/beta, resulting in enhanced gamma and spiking. To test the predictive routing model and its role in consciousness, we collected data from intracranial recordings of macaque monkeys during passive presentation of auditory oddballs before and after propofol-mediated loss of consciousness (LOC). In line with the predictive routing model, alpha/beta oscillations in the awake state served to inhibit the processing of predictable stimuli. Propofol-mediated LOC eliminated alpha/beta modulation by a predictable stimulus in the sensory cortex and alpha/beta coherence between sensory and frontal areas. As a result, oddball stimuli evoked enhanced gamma power, late period (>200 ms from stimulus onset) spiking, and superficial layer sinks in the sensory cortex. LOC also resulted in diminished decodability of pattern-level prediction error signals in the higher-order cortex. Therefore, the auditory cortex was in a disinhibited state during propofol-mediated LOC. However, despite these enhanced feedforward responses in the auditory cortex, there was a loss of differential spiking to oddballs in the higher-order cortex. This may be a consequence of a loss of within-area and interareal spike-field coupling in the alpha/beta and gamma frequency bands. These results provide strong constraints for current theories of consciousness., Competing Interests: Competing interests statement:E.N.B. holds patents on anesthetic state monitoring and control. E.N.B. holds founding interest in PASCALL, a start-up developing physiological monitoring systems; receives royalties from intellectual property through Massachusetts General Hospital licensed to Masimo. The interests of E.N.B. were reviewed and are managed by Massachusetts General Hospital and Mass General Brigham in accordance with their conflict of interest policies.

Only some subpopulations of natural killer (NK) cells have cytotoxic functionality, and the effects of anesthetics on these subpopulations are unknown. This study aimed to evaluate the in vitro effects of various anesthetics, both alone and in combination, on the distribution and cytotoxic function of NK cells and their subpopulations. Peripheral blood mononuclear cells (PBMCs) from eight healthy volunteers were treated for 4 h in vitro with dexmedetomidine, remifentanil, lidocaine, propofol, sevoflurane, and combinations in clinically relevant concentrations or left untreated. Flow cytometry was used to quantify the percentage of sampled NK cells and evaluate their distribution (CD56 bright CD16 neg , CD56 bright CD16 dim , CD56 dim CD16 neg , CD56 dim CD16 bright , and CD56 neg CD16 bright ) and cytotoxicity (Granzyme B (GrzB) and perforin) of NK cell subpopulations. Although the percentage of total NK cells did not change following exposure to anesthesia, the most important cytotoxic subpopulation (CD56 dim CD16 bright NK cells) decreased after exposure to both propofol (-3.58%, p = 0.045) and sevoflurane (-16.10%, p = 0.008) alone, and most combinations, especially in combination with lidocaine (propofol with lidocaine (-9.66%, p = 0.002) and sevoflurane with lidocaine (-21.90%, p < 0.001)). Dexmedetomidine and remifentanil had no effect on CD56 dim CD16 bright NK cells. Furthermore, no anesthetic regimen or combination altered the expression of GrzB and perforin in NK cells or NK cell subpopulations. In short, propofol and sevoflurane suppressed the highly cytotoxic phenotype (CD56 dim CD16 bright ) of NK cells, with those exposed to sevoflurane combinations showing greater reductions. Immunosuppression was intensified with the inclusion of lidocaine in the anesthetic regimen., Competing Interests: Tristan J. Vulcano: No conflicts of interest to report. Wayel H. Abdulahad: No conflicts of interest to report. Matijs van Meurs: No conflicts of interest to report. Rianne M. Jongman: No conflicts of interest to report. Michel M.R.F. Struys: The author has no conflicts of interest related to this manuscript. In general, his research group/department received (over the last 3 years) research grants and consultancy fees from Masimo (Irvine, CA, USA), Becton Dickinson (Eysins, Switzerland), Fresenius (Bad Homburg, Germany), Paion (Aachen, Germany), Medcaptain Europe (Andelst, The Netherlands), Baxter (Chicago, Il, USA), and HanaPharm (Seoul, Republic of Korea). He receives royalties on intellectual property from Demed Medical (Sinaai, Belgium) and Ghent University (Gent, Belgium). Dirk J. Bosch: No conflicts of interest to report.

Background: Sepsis often leads to cardiomyopathy, contributing to increased mortality rates. 2,6-Diisopropylphenol (propofol), an anesthetic, has demonstrated efficacy in protecting cardiomyocytes from cell death caused by hypoxia and reoxygenation. This study examined the effects of propofol on sepsis-associated myocardial dysfunction and explored the underlying mechanism of action., Methods: Mice and rat cardiomyocytes (H9C2 cell line) were used to establish a sepsis-induced myocardial dysfunction model. Lipopolysaccharides (LPS)-treated mice and H9C2 cells were treated with propofol, with rapamycin used for mechanistic studies in H9C2 cells. Cardiac function was evaluated by echocardiographic measurements. Heart tissues were stained with hematoxylin and eosin, and heart weight/body weight ratio along with the levels of cardiac biomarkers were measured using Enzyme Linked Immunosorbent Assay (ELISA). Activation of the mammalian target of rapamycin (mTOR) pathway was assessed by western blotting. Apoptosis in heart tissues and H9C2 cells was evaluated using Terminal deoxynucleotidyl transferase (TdT) dUTP nick end labeling (TUNEL) assay, and cell viability was quantified using Cell Counting Kit (CCK)-8 assay. Oxidative stress in H9C2 cells was assessed by measuring reactive oxygen species (ROS) levels through immunofluorescence staining and malondialdehyde (MDA) and superoxide dismutase (SOD) levels using ELISA., Results: Propofol reversed LPS-induced myocardial changes and cardiac dysfunction ( p < 0.05). In mouse tissues and H9C2 cells, propofol reversed LPS-induced mTOR pathway inhibition and apoptosis ( p < 0.001). Moreover, propofol alleviated oxidative stress in LPS-treated cells. The activation of the mTOR pathway by propofol, along with its inhibitory effects on oxidative stress and apoptosis in cardiomyocytes, was negated by rapamycin ( p < 0.001)., Conclusion: Propofol ameliorates sepsis-induced myocardial dysfunction triggered by LPS through the mTOR pathway, thereby promoting antioxidative stress and reducing cell apoptosis.

This study investigates the protective effects of propofol on the myocardium by inhibiting the expression of SLC16A13 through in vivo animal experiments, while also exploring its mechanism in ferroptosis to provide new strategies for preventing perioperative myocardial ischemia-reperfusion injury. We randomly divided 30 rats into three groups (n=10 each): sham surgery group, ischemia-reperfusion (I/R) group, and propofol pretreatment group. The results showed that compared with the sham surgery group, the I/R group had a significant decrease in cardiac function and an increase in infarct size. Propofol pretreatment effectively alleviated the damage caused by ischemia-reperfusion (I/R). In the next phase of the study, we administered the PPARα agonist GW7647 to artificially increase the expression of SLC16A13. Fifty rats were randomly divided into five groups (n=10 each), with the GW7647 pretreatment group and propofol+GW7647 pretreatment group added based on the previous three groups. Afterwards, we validated the in vivo results using H9C2 and further explored the mechanism by which propofol inhibits ferroptosis. The study found that L-lactic acid in myocardial tissue of the GW7647 group was further increased compared to the I/R group, and the degree of ferroptosis was aggravated. In addition, upregulation of SLC16A13 significantly inhibited the phosphorylation of AMPK, weakened the protective mechanism of AMPK, and exacerbated cardiac damage. However, propofol pretreatment can effectively inhibit the expression of SLC16A13, maintain normal myocardial cell morphology, and protect cardiac function. These results indicate that propofol inhibits the expression of SLC16A13, alleviates myocardial cell ferroptosis via the AMPK/GPX4 pathway, and reverses damage caused by myocardial ischemia-reperfusion., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Purpose: To determine the precise induction dose, an objective assessment of individual propofol sensitivity is necessary. This study aimed to investigate whether preinduction electroencephalogram (EEG) data are useful in determining the optimal propofol dose for the induction of general anesthesia in healthy adult patients., Methods: Seventy healthy adult patients underwent total intravenous anesthesia (TIVA), and the effect-site target concentration of propofol was observed to measure each individual's propofol requirements for loss of responsiveness. We analyzed preinduction EEG data to assess its relationship with propofol requirements and conducted multiple regression analyses considering various patient-related factors., Results: Patients with higher relative delta power (ρ = 0.47, p < 0.01) and higher absolute delta power (ρ = 0.34, p = 0.01) required a greater amount of propofol for anesthesia induction. In contrast, patients with higher relative beta power (ρ = -0.33, p < 0.01) required less propofol to achieve unresponsiveness. Multiple regression analysis revealed an independent association between relative delta power and propofol requirements., Conclusion: Preinduction EEG, particularly relative delta power, is associated with propofol requirements during the induction of general anesthesia. The utilization of preinduction EEG data may improve the precision of induction dose selection for individuals., (© 2024. The Author(s).)

The purpose of this study is to explore the shared molecular pathogenesis of traumatic brain injury (TBI) and high-grade glioma and investigate the mechanism of propofol (PF) as a potential protective agent. By analyzing the Chinese glioma genome atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases, we compared the transcriptomic data of high-grade glioma and TBI patients to identify common pathological mechanisms. Through bioinformatics analysis, in vitro experiments and in vivo TBI model, we investigated the regulatory effect of PF on extracellular matrix (ECM)-related genes through Prrx1 under oxidative stress. The impact of PF on BBB integrity under oxidative stress was investigated using a dual-layer BBB model, and we explored the protective effect of PF on tight junction proteins and ECM-related genes in mice after TBI. The study found that high-grade glioma and TBI share ECM instability as an important molecular pathological mechanism. PF stabilizes the ECM and protects the BBB by directly binding to Prrx1 or indirectly regulating Prrx1 through miRNAs. In addition, PF reduces intracellular calcium ions and ROS levels under oxidative stress, thereby preserving BBB integrity. In a TBI mouse model, PF protected BBB integrity through up-regulated tight junction proteins and stabilized the expression of ECM-related genes. Our study reveals the shared molecular pathogenesis between TBI and glioblastoma and demonstrate the potential of PF as a protective agent of BBB. This provides new targets and approaches for the development of novel neurotrauma therapeutic drugs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Abstract: 99m Tc-MAG3 diuresis renography is a noninvasive functional imaging technique used to assess clearance of radiotracer in a dilated urinary tract under high diuresis. It is commonly performed in patients to diagnose functionally significant urinary tract obstruction. In some pediatric patients, sedation is required to enable imaging. However, propofol, a commonly used IV sedative agent, is associated with altered renal hemodynamics. We report a case series of 3 pediatric patients at our institution who received propofol sedation to enable 99m Tc-MAG3 diuresis renography using a F+0 protocol, outlining that some "abnormal" studies were in fact assessed to be nondiagnostic., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Ischemic stroke is a leading cause of adult disability and death worldwide. The primary treatment for cerebral ischemia patients is to restore blood supply to the ischemic region as quickly as possible. However, in most cases, more severe tissue damage occurs, which is known as cerebral ischemia/reperfusion (I/R) injury. The pathological mechanisms of brain I/R injury include mitochondrial dysfunction, oxidative stress, excitotoxicity, calcium overload, neuroinflammation, programmed cell death and others. Propofol (2,6-diisopropylphenol), a short-acting intravenous anesthetic, possesses not only sedative and hypnotic effects but also immunomodulatory and neuroprotective effects. Numerous studies have reported the protective properties of propofol during brain I/R injury. In this review, we summarize the potential protective mechanisms of propofol to provide insights for its better clinical application in alleviating cerebral I/R injury., (© 2024. The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences.)

Background/aim: Propofol is a common anesthetic used during surgery. MircoRNA (miRNA), especially miR-4430, is currently a research hotspot in GBC. This study investigates whether propofol regulates GBC through the miR-4430/SLC19A3 axis., Materials and Methods: NOZ and SGC996 cells, human gallbladder cancer cell lines, were obtained from BLUEFBIO (Shanghai, China). The cells were treated with propofol, and the experimental setup included a control group. qRT-PCR was used to measure the content of miR-4430 and solute carrier family 19 member 3 (SLC19A3). The cell viability, migration, and apoptosis were analyzed by colony formation assay, wound healing assay, and flow cytometry, respectively. Western blot tested the levels of SLC91A3, cyclin D-dependent kinases 6 (CDK6), and Bax proteins. Mechanically, dual-luciferase reporter assay notarized the link of miR-4430 with SLC19A3., Results: Propofol significantly repressed the proliferation of GBC cells, as indicated by a pronounced reduction in colony formation in both NOZ and SGC996 cells (P = .025, 95% CI:1.2, 2.4). The inhibitory effect of propofol was reversed by the enhanced expression of miR-4430 in GBC cells. Furthermore, SLC19A3 was identified as a direct target of miR-4430. Silencing SLC19A3 reversed the altered cell behavior observed in propofol-treated GBC cells (P = .019, 95% CI:1.6, 3.5). Additionally, overexpression of SLC19A3 significantly attenuated both cell proliferation and migration influenced by miR-4430 in propofol-treated GBC cells (P = .034, 95% CI:1.4, 2.8)., Conclusion: Propofol changed the cell behaviors of GBC by modulating the miR-4430/SLC19A3 axis.

Background: The Eleveld pharmacokinetic-pharmacodynamic model for propofol predicts bispectral index (BIS) processed electroencephalogram values from estimated effect-site concentrations. We investigated agreement between measured and predicted BIS values during total intravenous anaesthesia (TIVA)., Methods: Forty participants undergoing lower limb surgery received TIVA using remifentanil target-controlled infusions and propofol by manually controlled, target-guided infusions based upon the Eleveld model and directed by two pharmacokinetic computer simulation applications: PKPD Tools and StelSim. We evaluated the predictive performance of the Eleveld model by calculating median prediction errors (BIS units) and by Bland-Altman analyses. We also performed |Bland-Altman analysis of supplementary data provided by the authors of the Eleveld model., Results: Whereas median prediction errors were small (MDPE -1.9, MDAPE 10), the ranges were wide (-18.5 to 24.3 and 1.7 to 24.3). The proportion of MDAPE >10 BIS units was 47.8%. Bland-Altman analysis showed a small mean bias (-0.52 BIS units) with wide limits of agreement (-27.7 to 26.2). Each participant's limits of agreement did not meet the requirements for declaring interchangeability between the two measurements. The measurement differences depended on the BIS values, as indicated by the positive slopes of the differences vs BIS values. Bland-Altman analysis of the Eleveld model supplementary data revealed similar results., Conclusion: BIS predictions by the Eleveld model should be interpreted with caution. In spite of the acceptable MDPE and MDAPE, there are unacceptable degrees of both within-subject and between-subject variation during propofol target-controlled infusions. This limits the use of adjusting targeted concentrations to achieve desired simulated BIS values with confidence., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Previous research has demonstrated that basal forebrain (BF) regulates arousal during propofol anesthesia. However, as the BF comprises cholinergic neurons alongside two other types of neurons, the specific role of cholinergic neurons has not been definitively elucidated. In our study, calcium signal imaging was utilized to monitor the real-time activities of cholinergic neurons in the BF during propofol anesthesia. Additionally, we selectively stimulated these neurons to investigate EEG and behavioral responses during propofol anesthesia. Furthermore, we specifically lesioned cholinergic neurons in the BF to investigate the sensitivity to propofol and the induction time. The results revealed that propofol suppressed calcium signals of cholinergic neurons within the BF following intraperitoneal injection. Notably, upon recovery of the righting reflex, the calcium signals partially recovered. Spectral analysis of the EEG elucidated that optical stimulation of cholinergic neurons led to a decrease in δ power underlie propofol anesthesia. Conversely, depletion of cholinergic neurons in the BF enhanced sensitivity to propofol and shortened the induction time. These findings clarify the role of cholinergic neurons in the anesthesia-arousal process, as well as the depth and the sensitivity of propofol anesthesia., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Although remimazolam is used as a general anesthetic in elderly patients due to its hemodynamic stability, the electroencephalogram characteristics of remimazolam are not well known. The purpose of this study was to identify the electroencephalographic features of remimazolam-induced unconsciousness in elderly patients and compare them with propofol., Methods: Remimazolam (n = 26) or propofol (n = 26) were randomly administered for anesthesia induction in surgical patients. The hypnotic agent was blinded only to the patients. During the induction of anesthesia, remimazolam was administered at a rate of 6 mg · kg-1 · h-1, and propofol was administered at a target effect-site concentration of 3.5 μg/ml. The electroencephalogram signals from eight channels (Fp1, Fp2, Fz, F3, F4, Pz, P3, and P4, referenced to A2, using the 10 to 20 system) were acquired during the induction of anesthesia and in the postoperative care unit. Power spectrum analysis was performed, and directed functional connectivity between frontal and parietal regions was evaluated using normalized symbolic transfer entropy. Functional connectivity in unconscious processes induced by remimazolam or propofol was compared with baseline. To compare each power of frequency over time of the two hypnotic agents, a permutation test with t statistic was conducted., Results: Compared to the baseline in the alpha band, the feedback connectivity decreased by averages of 46% and 43%, respectively, after the loss of consciousness induced by remimazolam and propofol (95% CI for the mean difference: -0.073 to -0.044 for remimazolam [P < 0.001] and -0.068 to -0.042 for propofol [P < 0.001]). Asymmetry in the feedback and feedforward connectivity in the alpha band was suppressed after the loss of consciousness induced by remimazolam and propofol. There were no significant differences in the power of each frequency over time between the two hypnotic agents (minimum q value = 0.4235)., Conclusions: Both regimens showed a greater decrease in feedback connectivity compared to a decrease in feedforward connectivity after loss of consciousness, leading to a disruption of asymmetry between the frontoparietal connectivity., (Copyright © 2024 American Society of Anesthesiologists. All Rights Reserved.)

Spinal cord ischemia-reperfusion injury (SCIRI) is a major contributor to neurological damage and mortality associated with spinal cord dysfunction. This study aims to explore the possible mechanism of Propofol and G-protein-coupled receptor-interacting protein 1 (GIT1) in regulating SCIRI in rat models. SCIRI rat models were established and injected with Propofol, over expression of GIT1 (OE-GIT1), or PI3K inhibitor (LY294002). The neurological function was assessed using Tarlov scoring system, and Hematoxylin & Eosin (H&E) staining was applied to observe morphology changes in spinal cord tissues. Cell apoptosis, blood-spinal cord barriers (BSCB) permeability, and inflammatory cytokines were determined by TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, evans blue (EB) staining, and enzyme-linked immuno sorbent assay (ELISA), respectively. Reverse transcription-quantitative polymerase chain reaction and western blot were used to detect the expression levels of GIT1, endothelial nitric oxide synthase (eNOS), PI3K/AKT signal pathway and apoptosis-related proteins. SCIRI rats had decreased expressions of GIT1 and PI3K/AKT-related proteins, whose expressions can be elevated in response to Propofol treatment. LY294002 can also decrease GIT1 expression levels in SCIRI rats. Propofol can attenuate neurological dysfunction induced by SCIRI, decrease spinal cord tissue injury and BSCB permeability in addition to suppressing cell apoptosis and inflammatory cytokines, whereas further treatment by LY294002 can partially reverse the protective effect of Propofol on SCIRI. Propofol can activate PI3K/AKT signal pathway to increase GIT1 expression level, thus attenuating SCIRI in rat models., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The full mechanism of action of propofol, a commonly administered intravenous anesthetic drug in clinical practice, remains elusive. The focus of this study was the role of GABAergic neurons which are the main neuron group in the ventral pallidum (VP) closely associated with anesthetic effects in propofol anesthesia. The activity of VP GABAergic neurons following propofol anesthesia in Vgat-Cre mice was observed via detecting c-Fos immunoreactivity by immunofluorescence and western blotting. Subsequently, chemogenetic techniques were employed in Vgat-Cre mice to regulate the activity of VP GABAergic neurons. The role of VP GABAergic neurons in generating the effects of general anesthesia induced by intravenous propofol was further explored through behavioral tests of the righting reflex. The results revealed that c-Fos expression in VP GABAergic neurons in Vgat-Cre mice dramatically decreased after propofol injection. Further studies demonstrated that chemogenetic activation of VP GABAergic neurons during propofol anesthesia shortened the duration of anesthesia and promoted wakefulness. Conversely, the inhibition of VP GABAergic neurons extended the duration of anesthesia and facilitated the effects of anesthesia. The results obtained in this study suggested that regulating the activity of GABAergic neurons in the ventral pallidum altered the effect of propofol on general anesthesia., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

Background: The pharmacodynamics of propofol in children have previously been described with the proprietary bispectral index (BIS) as an effect-site marker, and it has been suggested that the rate of onset of propofol might be age dependent, that is, a shorter time to peak effect in younger children. However, these analyses were potentially confounded by co-administered drugs, in particular opioids and benzodiazepines. Thus, the goal of this prospective study was to characterize the influence of age and weight on the onset of hypnotic effects from propofol, reflected by the time to peak of propofol effect-site concentration in the absence of additional drugs., Methods: A total of 46 healthy children aged 2-12 years presenting for elective surgery were included in our observational cohort study. Solely propofol was administered via a target-controlled infusion pump programmed with the Paedfusor pharmacokinetic model. The BIS and infusion pump data were recorded. The effect of an induction "bolus" was recorded having stopped the pump once a propofol plasma target concentration of 7 μg.mL -1 was achieved. A direct-response and an indirect-response model in the context of nonlinear mixed-effects modeling was used to characterize and compare BIS data in children aged 2-6 years and older children aged 8-12 years., Results: Time to peak of propofol effect-site concentration had a difference (p-value <.01) for age and weight, that is 84 [74, 96] (median [IQR] secs for children aged 2-6 years vs. 99 [91, 113] secs for children aged 8-12 years and 82 [71, 95] secs for weight 11-25 kg vs. 99 [91, 114] secs for weight 30-63 kg). The plasma effect-site equilibration rate constant for propofol had a heterogeneous distribution with a median of 2.36 (IQR: 2.05-2.93; range: 0.83-7.31) per minute but showed a weight-dependent effect in patients with weight below 45 kg., Conclusions: In children, the age and weight have an influence on time to peak effect of propofol. In the absence of opioids and benzodiazepines, time to peak effect was approximately 20% longer in children aged 8-12 years as compared to younger children. Such clinically relevant age and weight effects are an important consideration in the individualized titration of propofol dosing., (© 2024 The Author(s). Pediatric Anesthesia published by John Wiley & Sons Ltd.)

Subarachnoid hemorrhage (SAH) is a devastating stroke caused by ruptured intracranial aneurysms, leading to blood accumulation around the brain. Early brain injury (EBI) within 72 h post-SAH worsens prognosis, primarily due to intense neuroinflammation. Microglia, pivotal in central nervous system defense and repair, undergo M1 to M2 polarization post-SAH, with M1 exacerbating neuroinflammation. Propofol (PPF), an anesthetic with anti-inflammatory properties, shows promise in mitigating neuroinflammation in SAH by modulating microglial activation. It likely acts through microRNAs like miR-140-5p, which attenuates microglial activation and inflammation by targeting TREM-1 and the NF-κB pathway. Understanding these mechanisms could lead to new therapeutic approaches for SAH-related EBI. In this study, BV-2 cell was used to establish in vitro model of SAH, and the expression of miR-140-5p and TREM-1 was detected after modeling. Microglial activity, apoptosis, the inflammatory pathway and response, oxidative damage, and M1/M2 polarization of microglia were evaluated by drug administration or transfection according to experimental groups. Finally, the targeting relationship between miR-140-5p and TREM-1 was verified by dual luciferase reporter assays, and the effect of PPF on the miR-140-5p/TREM-1/NF-κB signaling cascade was evaluated by RT‒qPCR or Western blotting. PPF effectively mitigates apoptosis, neuroinflammation, oxidative damage, and M1 microglial polarization in SAH. In SAH cells, PPF upregulates miR-140-5p and downregulates TREM-1. Mechanistically, PPF boosts miR-140-5p expression, while TREM-1, a downstream target of miR-140-5p, inhibits NF-κB signaling by regulating TREM-1, promoting M1 to M2 microglial polarization. Reduced miR-140-5p or increased TREM-1 counters PPF's therapeutic impact on SAH cells. In conclusion, PPF plays a neuroprotective role in SAH by regulating the miR-140-5p/TREM-1/NF-κB signaling axis to inhibit neuroinflammation and M1 polarization of microglia.

Background: Most ovarian cancer cases are diagnosed at an advanced stage, leading to poor outcomes and a relatively low 5-year survival rate. While tumor resection in the early stages can be highly effective, recurrence following primary treatment remains a significant cause of mortality. Propofol is a commonly used intravenous anesthetic agent in cancer resection surgery. Previous research has shown that propofol anesthesia was associated with improved survival in patients undergoing elective surgery for epithelial ovarian cancer. However, the underlying antitumor mechanisms are not yet fully understood., Methods: This study aimed to uncover the antitumor properties of propofol alone and combined with cisplatin or doxorubicin, in human SKOV3 and OVCAR3 ovarian cancer cells. We applied flowcytometry analysis for mitochondrial membrane potential, apoptosis, and autophagy, colony formation, migration, and western blotting analysis., Results: Given that chemotherapy is a primary clinical approach for managing advanced and recurrent ovarian cancer, it is essential to address the limitations of current chemotherapy, particularly in the use of cisplatin and doxorubicin, which are often constrained by their side effects and the development of resistance. First of all, propofol acted synergistically with cisplatin and doxorubicin in SKOV3 cells. Moreover, our data further showed that propofol suppressed colony formation, disrupted mitochondrial membrane potential, and induced apoptosis and autophagy in SKOV3 and OVCAR3 cells. Finally, the effects of combined propofol with cisplatin or doxorubicin on mitochondrial membrane potential, apoptosis, autophagy, and epithelial-mesenchymal transition were different in SKOV3 and OVCAR3 cells, depending on the p53 status., Conclusion: In summary, repurposing propofol could provide novel insights into the existing chemotherapy strategies for ovarian cancer. It holds promise for overcoming resistance to cisplatin or doxorubicin and may potentially reduce the required chemotherapy dosages and associated side effects, thus improving treatment outcomes., (© 2024. The Author(s).)

Research into the role of thalamocortical circuits in anesthesia-induced unconsciousness is difficult due to anatomical and functional complexity. Prior neuroimaging studies have examined either the thalamus as a whole or focused on specific subregions, overlooking the distinct neuronal subtypes like core and matrix cells. We conducted a study of heathy volunteers and functional magnetic resonance imaging during conscious baseline, deep sedation, and recovery. We advanced the functional gradient mapping technique to delineate the functional geometry of thalamocortical circuits, within a framework of the unimodal-transmodal functional axis of the cortex. Here we show a significant shift in this geometry during deep sedation, marked by a transmodal-deficient geometry. This alteration is closely linked to the spatial variations in the matrix cell composition within the thalamus. This research bridges cellular and systems-level understanding, highlighting the crucial role of thalamic core-matrix functional architecture in understanding the neural mechanisms of states of consciousness., (© 2024. The Author(s).)

The aim of this study was to investigate the mechanism by which propofol reduces postoperative cognitive dysfunction after splenectomy in aged rats. The rats in the model group and propofol group were subjected to splenectomy, and anesthetized with isoflurane and propofol, respectively. Utilizing the western blotting to assess the expression of sirtuin-1 (SIRT1) in the hippocampus. Molecular docking technology was used to predict the binding ability of propofol and SIRT1. Behavioral tests were performed using the Morris water maze, and the hippocampus was isolated for mechanistic investigations. Molecular docking showed that propofol and SIRT1 had a strong binding affinity. The expression of SIRT1 and its related proteins Nrf2, HO-1, NQO1, and GPX4 in the model rats was decreased compared with the sham group. Moreover, the model group exhibited cognitive decline, such as extended escape latency and decreased number of platform crossings. Pathological analysis showed that the number of apoptotic neurons, the levels of oxidative stress and neuroinflammation, the iron deposition, and the expressions of ACSL4 and TFR1 were increased, while the expressions of SLC7A11 and FTH1 were decreased in the hippocampal CA1 region within the model group. These pathological changes in the propofol group were, however, less than those in the model group. Nevertheless, the SIRT1 inhibitor increased these pathological changes compared with the propofol group. Compared with isoflurane, propofol inhibits ferroptosis in the hippocampus of splenectomized rats by causing less downregulation of the SIRT1/Nrf2/GPX4 pathway, thereby reducing the negative impact on cognitive function., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Bladder cancer is a highly prevalent malignancy. Asiaticoside (AC), a triterpenoid derivative, exhibits antitumor effect on different tumors. This study aimed to explore the role and mechanism of AC on bladder cancer. J82 and T24 cells were treated with AC and/or propofol, and nude mice were subcutaneously administrated with T24 cells. The effect and mechanism of AC and/or propofol were explored by cell counting kit-8, transwell, flow cytometry, enzyme-linked immunosorbent assay, immunohistochemistry and western blot assays both in vitro and in vivo. Cell viability of J82 and T24 cells was inhibited by AC with a IC50 value of 2.43 μM and 2.16 μM, and by propofol with a IC50 value of 42.51 μM and 48.37 μM, respectively. AC or propofol alone decreased cell proliferation, invasion, and immune escape with the increased ferroptosis, as well as downregulating the level of the PI3K/AKT pathway in both animal and cell experiments. The effect of propofol on the above-mentioned indicators was further enhanced with the co-treatment of AC in vitro and in vivo. Taken together, AC promoted the ameliorative effect of propofol on bladder cancer involved in PI3K/AKT pathway., (© 2024 Wiley Periodicals LLC.)

Background: To address the intricate interplay between surgical anesthesia, hippocampal apoptosis, and early cognitive dysfunction in rats, this study delves into the impact of dexmedetomidine (DEX). With a focus on understanding the alterations in the PI3K/Akt pathway, our investigation aims to shed light on the comprehensive dynamics of these processes., Methods: Sixty healthy Sprague-Dawley rats were randomly divided into three groups: controls (intraperitoneal saline injection), group A (intraperitoneal propofol injection), and group A + DEX (intraperitoneal propofol and DEX injection), with 20 rats in each group. Cognitive function in the three groups was evaluated using [specify the cognitive function tests, e.g., Morris Water Maze]. The assessment was conducted at various postoperative time points. We employed Hematoxylin-eosin (HE) staining, flow cytometry (FC), Western blot (WB), and real-time fluorescence quantitation polymerase chain reaction (RT-qPCR) to examine hippocampal apoptosis and gene expression., Results: Rats in groups A and A + DEX exhibited higher cognitive scores (NSS) and escape latencies at each postoperative time point, along with a lower proportion of swimming distance (SD) in the target quadrant (TQ) compared to controls. Group A + DEX demonstrated lower NSS and escape latency than controls, accompanied by a higher proportion of SD in TQ. Apoptosis rates of hippocampal cells were higher in groups A and A + DEX than in controls, although they were relatively lower in group A + DEX (P < .05). Regarding gene expression, the relative expression (RE) of Bcl-2, PI3K, pAkt, mRNA expression of Bcl-2 and PI3K, and Bax and caspase3 were altered. Group A + DEX showed higher RE of Bcl-2, PI3K, pAkt, mRNA expression of Bcl-2 and PI3K, and lower Bax and caspase3 than group A (P < .05). For a detailed understanding of the magnitude of these changes, specific values or ranges are provided in the subsequent results section., Conclusion: In conclusion, the combined use of surgical anesthesia with DEX demonstrates a modulatory effect on the PI3K/Akt signaling pathway. This intervention proves effective in reducing hippocampal cell apoptosis post-surgery, thereby alleviating neurological impairments and ameliorating early cognitive dysfunction in rats. Our findings underscore the potential therapeutic impact of DEX in enhancing cognitive outcomes following surgical procedures. The observed reduction in hippocampal cell apoptosis and improvement in cognitive function suggest that DEX may hold promise as a neuroprotective agent in the perioperative setting. These outcomes highlight the clinical relevance of considering DEX as an adjunctive therapy to mitigate cognitive dysfunction associated with surgery. Further investigations and clinical trials are warranted to validate and extend these findings, potentially offering a novel avenue for improving patient outcomes and advancing perioperative care strategies.

Objective: To evaluate the propofol-sparing and hemodynamic effects of guaifenesin administered for co-induction of anesthesia in sheep., Study Design: Prospective, blinded, two-way crossover experimental study., Animals: Thirteen healthy adult female sheep., Methods: Anesthesia was induced without premedication with intravenous (IV) guaifenesin 5% at 100 mg kg -1 (GGE) or an equivalent volume of physiologic saline (SAL), followed by IV propofol at a controlled rate (1 mg kg -1 min -1 ). Heart rate (HR), respiratory rate and oscillometric noninvasive arterial blood pressure (NIBP) were recorded at baseline after co-induction administration, following endotracheal intubation and every 2 minutes thereafter for 10 minutes. Propofol doses required to achieve intubation after each co-induction treatment were compared by independent Student's t-test. Values of p < 0.05 were considered statistically significant., Results: The propofol dose required (mean ± standard deviation) to achieve intubation was significantly lower (p = 0.001) in the GGE treatment (3.40 ± 0.74 mg kg -1 ) than in the SAL treatment (5.94 ± 1.09 mg kg -1 ). HR was increased after anesthetic induction compared with baseline in both treatments. HR was generally lower in the GGE treatment than in the SAL treatment. NIBP did not vary between GGE and SAL treatments., Conclusions and Clinical Relevance: Guaifenesin, when administered as a co-induction agent with propofol in sheep, reduces propofol dose requirements and maintains hemodynamic variables within a clinically acceptable range., (Published by Elsevier Ltd.)

Objective: To compare the effects of propofol, ketamine-propofol and isoflurane, at similar anesthetic depth, on cardiopulmonary variables in unpremedictated chickens., Study Design: Prospective, randomized, crossover experimental trial., Animals: A total of 10 male Leghorn domestic chickens, aged 3 months and body mass 1.4-2.0 kg., Methods: Birds were randomly assigned to each of three anesthetic protocols, 7 days apart: intravenous propofol, intravenous ketamine-propofol or isoflurane. Anesthesia was induced (indicated by loss of righting reflex and tracheal intubation) and maintained with propofol (10 mg kg -1 minute -1 , then 1.1 mg kg -1 minute -1 ), ketamine-propofol (5 mg mL -1 ketamine and 5 mg mL -1 propofol combined; 10 mg kg -1 minute -1 , then 1.1 mg kg -1 minute -1 ) or isoflurane [5% vaporizer setting initially, then end-tidal concentration (Fe'Iso) of 2%] for 65 minutes. Anesthesia was maintained at a similar anesthetic depth based upon positive or negative responses to toe pinch. Heart rate (HR), respiratory rate (f R ), noninvasive arterial blood pressure and arterial blood gases were measured during anesthesia. Propofol or ketamine-propofol infusion rates and Fe'Iso required to prevent movement in response to a noxious stimulus and recovery times were recorded., Results: Anesthesia induction dose was 9.0 ± 0.8 (mean ± SD) and 12.2 ± 0.3 mg kg -1 for propofol and ketamine-propofol, respectively. Propofol and ketamine-propofol infusion rates and Fe'Iso required to prevent movement in response to the noxious stimulus were 0.88 ± 0.14 mg kg -1 minute -1 , 0.92 ± 0.14 mg kg -1 minute -1 and 1.45 ± 0.28%, respectively. Cardiopulmonary variables remained clinically acceptable, but ketamine-propofol was associated with a significantly higher HR (p = 0.0001) and lower f R (p = 0.0001). Time to extubation did not differ among treatments., Conclusions and Clinical Relevance: Cardiovascular and respiratory variables were maintained within normal ranges in all treatments. Coadministration of ketamine with propofol significantly reduced the induction and maintenance dose of propofol., (Copyright © 2024 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Acute lung injury (ALI) frequently occurs after video-assisted thoracoscopic surgery (VATS). Ferroptosis is implicated in several lung diseases. Therefore, the disparate effects and underlying mechanisms of the two commonly used anesthetics (sevoflurane (Sev) and propofol) on VATS-induced ALI need to be clarified. In the present study, enrolled patients were randomly allocated to receive Sev (group S) or propofol anesthesia (group P). Intraoperative oxygenation, morphology of the lung tissue, expression of ZO-1, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), superoxide dismutase (SOD), glutathione (GSH), Fe 2+ , glutathione peroxidase 4 (GPX4), and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in the lung tissue as well as the expression of TNF-α and IL-6 in plasma were measured. Postoperative complications were recorded. Of the 85 initially screened patients scheduled for VATS, 62 were enrolled in either group S (n = 32) or P (n = 30). Compared with propofol, Sev substantially (1) improved intraoperative oxygenation; (2) relieved histopathological lung injury; (3) increased ZO-1 protein expression; (4) decreased the levels of TNF-α and IL-6 in both the lung tissue and plasma; (5) increased the contents of GSH and SOD but decreased Fe 2+ concentration; (6) upregulated the protein expression of p-AKT, Nrf2, HO-1, and GPX4. No significant differences in the occurrence of postoperative outcomes were observed between both groups. In summary, Sev treatment, in comparison to propofol anesthesia, may suppress local lung and systemic inflammatory responses by activating the PI3K/Akt/Nrf2/HO-1 pathway and inhibiting ferroptosis. This cascade of effects contributes to the maintenance of pulmonary epithelial barrier permeability, alleviation of pulmonary injury, and enhancement of intraoperative oxygenation in patients undergoing VATS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Postoperative cognitive dysfunction (POCD) encompasses a spectrum of cognitive impairments following surgery, attributed to disruptions in brain homeostasis. The pathogenesis involves glutamate toxicity, GABA receptor dysfunction, and alterations in NMDA and AMPA receptors. This study aimed to investigate the impact of pre-anesthetic amantadine administration on postoperative recovery time, POCD, and stress-related pain levels when combined with propofol anesthesia., Methods: Twenty-four adult male BALB/C mice were divided into four groups: Control, Propofol, Amantadine, and Amantadine+Propofol. Amantadine and propofol doses were administered intraperitoneally based on previous literature. Recovery time, pain levels (assessed via tail pinch and hot plate tests), cognitive functions (evaluated through Morris Water Maze), and locomotor activity (measured via Open Field Test) were recorded., Results: Amantadine administration significantly reduced recovery time from propofol anesthesia, prolonged pain perception, and preserved cognitive functions compared to propofol alone. The time spent in the target quadrant in the Morris Water Maze was significantly longer in groups receiving amantadine. Additionally, the distance covered until finding the platform was significantly shorter in the propofol-only group., Discussion: Amantadine's neuroprotective effects, attributed to its antagonistic action on glutamate and NMDA receptors, mitigate the detrimental effects of propofol on cognitive function and pain perception. This study highlights the potential of combining amantadine with propofol to enhance postoperative outcomes., Conclusion: Amantadine administration before propofol anesthesia positively influenced postoperative recovery, cognitive function preservation, and stress-related pain perception in mice. These findings suggest a potential therapeutic strategy to mitigate POCD and pain associated with surgery., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Neuron excitotoxic damage induced by extracellular glutamate accumulation pathologically is one of the main mechanisms of depression. Glutamate transporter-1 (GLT-1) expressed in astrocyte is responsible for glutamate clearance to maintain glutamate balance. Electroconvulsive therapy (ECT) is prevalently recommended for severe depression due to its significant anti-depressant effect. Esketamine could offer advantages of rapid anti-depressant effect and neuron protection. The aim of this study is to investigate the anti-depressant efficacy of esketamine plus ECT, and further to explore the mechanism. Firstly, total 12 patients were randomized into anesthesia with propofol (P) or propofol+esketamine (PK) before ECT. 24-Hamilton Depression Scale (HAMD) was used to evaluate the severity of depression after each ECT. Then, depressive rat model was built using chronic unpredictable mild stress method, and subsequently received infusion of esketamine (5 mg/kg) or saline before ECT treatment (0.5 mA; 100 V) for consecutive 10 days. Tests including sucrose preference test, open field test and forced swimming test were used to evaluate depression-like behaviors. In next experiments, rats were injected with RIL, DHK or LY294002 intracerebroventricularly for continuous 10 days before individual treatment. After the fifth and sixth ECT, PK group displayed lower HAMD score compared to P group. In rat model, we found that esketamine plus ECT could significantly improve depression-like behaviors and decrease glutamate level. Esketamine and ECT could both activate PI3K/Akt/GLT-1 pathway. The GLT-1 agonist RIL made equivalent effect as esketamine plus ECT. Furthermore, after using PI3K/Akt inhibitor LY294002 and GLT-1 inhibitor DHK, esketamine plus ECT could neither improve depression-like symptoms, nor upregulate GLT-1 level. Our present study suggested that esketamine plus ECT could dramatically improve depression symptom. The activation of PI3K/Akt/GLT-1 pathway may be the potential mechanism., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Chaojin Chen reports financial support was provided by Guangzhou Association for Science and Technology. Chaojin Chen reports financial support was provided by Third Affiliated Hospital of Sun Yat-Sen University. Shaoli Zhou reports financial support was provided by Guangdong Pharmaceutical Association Foundation. Chaojin Chen reports financial support was provided by Guangdong Province-Regional Innovation Capacity and Support System Construction. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Surgical resection is the best-known approach for breast cancer treatment. However, post-operative metastases increase the rate of death. The potential effect of anesthetic drugs on long-term tumor growth, risk of metastasis, and recurrence after surgery has been investigated in cancer patients. However, the underlying mechanisms remain unclear. Therefore, we aimed to elucidate the anti-metastatic effect of lidocaine combined with common anesthetics and its mechanisms of action on lung metastasis in breast cancer models. The combination of lidocaine with propofol or sevoflurane inhibited the growth of TNBC cells compared to treatment alone. In addition, the combination effectively inhibited cancer cell migration and invasion. It suppressed tumor growth and increased the survival rate in breast 4 T1 orthotopic models. More importantly, it inhibited lung metastasis and recurrence compared with groups treated with a single anesthetic. In co-culture with TAMs and TNBC cells, lidocaine not only reduced M2-tumor-associated macrophages (TAM) that were increased by sevoflurane or propofol but also increased M1 macrophage polarization, impeding tumor growth in TNBC. Also, we found that the transforming growth factor-β (TGF-β) derived from TAMs increased EMT signaling in TNBC cells, and that lidocaine affected cancer cells as well as M2-TAMs, inducing M2 to M1 reprogramming and decreasing TGF-β/Smads-mediated EMT signaling in TNBC cells, leading to inhibition of cancer metastasis and recurrence. These findings suggest lidocaine combined with general anesthetics as a potential therapeutic approach for the inhibition of recurrence and metastasis of breast cancer patients undergoing curative resection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

This study evaluated the influence of gabapentin on sedation, propofol dosage, and physiological variables in cats premedicated with acepromazine and methadone. Thirty-four cats were randomly assigned to receive 100 mg of oral gabapentin (Gabapentin group) or placebo (Control group) 100 min before intramuscular premedication with acepromazine (0.05 mg/kg) plus methadone (0.3 mg/kg). Variables recorded included sedation, using the Dynamic Interactive Visual Analog Scale (DIVAS, range 0-100 mm) and a Numeric Descriptive Scale (NDS, range 0-14), heart rate, respiratory rate and Doppler systolic arterial pressure (SAP). All variables were measured before (T0), 100 min after administration of gabapentin or placebo (T1), and 30 min after premedication (T2). Physiological variables were also recorded after anesthetic induction with propofol (T3). At T2, NDS scores were higher in Gabapentin than the Control group [median (interquartile range): 4 (2-5) versus 2 (1-4), p = 0.028], whereas DIVAS scores were not significantly different [Control: 9 (4-13); Gabapentin: 12 (5-32)]. Despite the significant difference between groups in NDS scores, overall sedation scores were mild at T1 and T2 regardless of gabapentin administration. The propofol dosage did not differ between groups. The most concerning adverse effect was arterial hypotension (SAP < 90 mmHg), recorded only at T3 in 71% of cats in the Control group and 100% in the Gabapentin group, without significant difference between groups. Administration of gabapentin before premedication with acepromazine and methadone in healthy cats did not result in a clinically significant influence on sedation levels, physiological variables, or propofol dosage required for anesthesia induction., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Competing Interests: The authors report no financial support and potential conflicts of interest for this communication.

Remote ischemic preconditioning (RIPC) reduces ischemia-reperfusion injury in aortocoronary bypass surgery, potentially via extracellular vesicles (EVs) and their micro-RNA content. Clinical data implicate that propofol might inhibit the cardioprotective RIPC effect. This prospective, randomized study investigated the influence of different anesthetic regimes on RIPC efficacy and EV micro-RNA signatures. We also assessed the impact of propofol on cell protection after hypoxic conditioning and EV-mediated RIPC in vitro. H9c2 rat cardiomyoblasts were subjected to hypoxia, with or without propofol, and subsequent simulated ischemia-reperfusion injury. Apoptosis was measured by flow cytometry. Blood samples of 64 patients receiving anesthetic maintenance with propofol or isoflurane, along with RIPC or sham procedures, were analyzed, and EVs were enriched using a polymer-based method. Propofol administration corresponded with increased Troponin T levels (4669 ± 435.6 pg/mL), suggesting an inhibition of the cardioprotective RIPC effect. RIPC leads to a notable rise in miR-21 concentrations in the group receiving propofol anesthesia (fold change 7.22 ± 6.6). In vitro experiments showed that apoptosis reduction was compromised with propofol and only occurred in an EV-enriched preconditioning medium, not in an EV-depleted medium. Our study could clinically and experimentally confirm propofol inhibition of RIPC protection. Increased miR-21 expression could provide evidence for a possible inhibitory mechanism.

The objectives of this prospective, randomized, blinded, crossover, experimental study were to detect the potential anaesthetic- and analgesic-sparing effects of classical music provided to dogs undergoing skin surgery, and to investigate the role of substance P as an intraoperative pain indicator. Twenty dogs were included, each subjected to three different treatments: Chopin music, Mozart music and no music. They were premedicated with acepromazine, butorphanol and meloxicam and anaesthetized with propofol and isoflurane. Fentanyl was used as rescue analgesia. The anaesthetic depth was monitored by using the bispectral index along with standard anaesthetic monitoring, and autonomic nervous system responses were used to monitor the adequacy of analgesia. Furthermore, measurements of substance P serum concentration were carried out. Dogs exposed to music required less isoflurane and fentanyl. Furthermore, a statistically significant effect of time on substance P concentration was observed regardless of exposure to music, and there was a significant interaction effect between different timepoints and the type of acoustic stimulus. Classical music seems to have an isoflurane and fentanyl sparing effect on dogs undergoing minor surgery. Following surgical stimulation, the serum substance P concentration increases rapidly, and thus appears to be a potentially useful pain indicator., (© 2024. The Author(s).)

Every day, hundreds of thousands of people undergo general anesthesia. One hypothesis is that anesthesia disrupts dynamic stability-the ability of the brain to balance excitability with the need to be stable and controllable. To test this hypothesis, we developed a method for quantifying changes in population-level dynamic stability in complex systems: delayed linear analysis for stability estimation (DeLASE). Propofol was used to transition animals between the awake state and anesthetized unconsciousness. DeLASE was applied to macaque cortex local field potentials (LFPs). We found that neural dynamics were more unstable in unconsciousness compared with the awake state. Cortical trajectories mirrored predictions from destabilized linear systems. We mimicked the effect of propofol in simulated neural networks by increasing inhibitory tone. This in turn destabilized the networks, as observed in the neural data. Our results suggest that anesthesia disrupts dynamical stability that is required for consciousness., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

General anesthesia is thought to suppress the immune system and negatively affect postoperative infection and the long-term prognosis of cancer. However, the mechanism underlying immunosuppression induced by general anesthetics remains unclear. In this study, we focused on propofol, which is widely used for sedation under general anesthesia and intensive care and examined its effects on the T cell function and T cell-dependent immune responses. We found that propofol suppressed T cell glycolytic metabolism, differentiation into effector T cells, and cytokine production by effector T cells. CD8 T cells activated and differentiated into effector cells in the presence of propofol in vitro showed reduced antitumor activity. Furthermore, propofol treatment suppressed the increase in the number of antigen-specific CD8 T cells during Listeria infection. In contrast, the administration of propofol improved inflammatory conditions in mouse models of inflammatory diseases, such as OVA-induced allergic airway inflammation, hapten-induced contact dermatitis, and experimental allergic encephalomyelitis. These results suggest that propofol may reduce tumor and infectious immunity by suppressing the T cell function and T cell-dependent immune responses while improving the pathogenesis and prognosis of chronic inflammatory diseases by suppressing inflammation., (© 2024. The Author(s).)