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AIMS/INTRODUCTION: As a common complication in elderly patients after surgery/anesthesia, postoperative cognitive dysfunction (POCD) is mainly characterized by memory, attention, motor, and intellectual retardation. Neuroinflammation is one of the most uncontroversial views in POCD. The sevoflurane-induced neurotoxicity has attracted widespread attention in recent years. However, its mechanism has not been determined. This study aimed to observe the effects of sevoflurane on cognitive function and the changes in inflammatory indices and autophagy protein expression in the prefrontal cortex in aged rats. METHOD: Before the experiment, D-galactose was diluted with normal saline into a liquid with a concentration of 125 mg/kg and injected subcutaneously into the neck and back of rats for 42 days to establish the aging rat model. Morris water maze experiments were performed, including positioning navigation (5 days) and space exploration (1 day). The POCD model was established by 3.2% sevoflurane inhalation. The rats were treated with or without MCC950, a potent and selective nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inhibitor, followed by autophagy agonists and autophagy inhibitors. The expression levels of inflammasome-related protein NLRP3 and autophagy-related proteins LC3B and P62 were detected to test the behavior of rats with a water maze. RESULTS: We found that sevoflurane exposure affected learning and working memory ability in aged rats. We also observed microglia activation in the prefrontal cortex. NLRP3 protein expression was significantly upregulated after sevoflurane inhalation. NLRP3 inflammasome activation induced increased expression and mRNA expression of cleaved Caspase-1 and inflammatory cytokines IL-1ß and IL-18, and increased secretion of peripheral proinflammatory cytokines. The inhibitor MCC950 was used to improve cognitive ability and inflammation in rats and inhibit the secretion of cytokines. In addition, we demonstrated that significant inhibition of autophagy (decreased LC3-II/I and increased P62) was accompanied by increased activation of NLRP3 inflammasomes and more severe neural cell damage. However, autophagy inhibitor rapamycin administration to activate autophagy resulted in the inhibition of NLRP3 inflammasomes, ultimately attenuating neuronal injury. CONCLUSIONS: The activation of autophagy suppressed the formation of NLRP3 inflammasomes. It also alleviated cognitive impairment in aged rats.
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Disfunção Cognitiva , Inflamassomos , Ratos , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Sevoflurano/farmacologia , Autofagia , Citocinas/metabolismo , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Proteínas de TransporteRESUMO
BACKGROUND: The aim of the study was to determine the effects of repeated anesthesia exposure across postnatal development. METHODS: Seventy-two newborn Sprague-Dawley rats were randomly divided into Sev group and Con-aged group. Sev groups were exposed to 2.6% sevoflurane for 2 h on postnatal day (P) 7, P14, and P21; the Con groups only received carrier gas for 2 h. Learning and memory were evaluated using the MWM test at P31 (juvenile), P91 (adult), and 18 months postnatally (aged). The relative expression of APP and Mapt mRNA was detected by RT-PCR, while Aß, tau, and P-tau protein levels were analyzed by immunohistochemistry. RESULTS: After repeated inhalation of sevoflurane, MWM test performance was significantly decreased in the Sev-aged group compared to the Con-aged group (P > 0.05). The relative expression of APP and Mapt mRNA was not significantly different between groups in each growth period (P > 0.05). The tau expression in the juvenile hippocampal CA1, CA3, and dentate gyrus regions increased markedly in the Sev group, while P-tau only increased in the hippocampal CA3 region in the Sev-adult group. The expression of tau, P-tau, and Aß in the hippocampal regions was upregulated in the Sev-aged group. CONCLUSIONS: Multiple exposures to sevoflurane across postnatal development can induce or aggravate cognitive impairment in old age. IMPACT: Whether multiple sevoflurane exposures across postnatal development cause cognitive impairment in childhood, adulthood, or old age, as well as the relationship between sevoflurane and the hippocampal Aß, tau, and P-tau proteins, remains unknown. This study's results demonstrate that multiple exposures to sevoflurane across postnatal development do not appear to affect cognitive function in childhood and adulthood; however, multiple exposures may lead to a cognitive function deficit in old age. The underlying mechanism may involve overexpression of the tau, P-tau, and Aß proteins in the hippocampus.
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Anestésicos Inalatórios , Disfunção Cognitiva , Éteres Metílicos , Ratos , Animais , Sevoflurano/efeitos adversos , Sevoflurano/metabolismo , Ratos Sprague-Dawley , Éteres Metílicos/toxicidade , Éteres Metílicos/metabolismo , Anestésicos Inalatórios/toxicidade , Anestésicos Inalatórios/metabolismo , Aprendizagem em Labirinto , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/psicologia , Cognição , Hipocampo/metabolismoRESUMO
INTRODUCTION: Studies have suggested dexmedetomidine (DEX) as a potential antidepressant. However, no relevant research exists on its effects and mechanisms in curing depression caused by chronic pain. Therefore, an understanding of DEX's role in depressive disorders proposes new approaches for antidepressant treatment. METHODS: In this study, C57Bl/6 mice (n = 80) were divided into sham (n = 8) and chronic constrictive injury (CCI, n = 72) groups. The CCI group was further divided into six subgroups: CCI + normal saline (NS), CCI + DEX6.25, CCI + DEX12.5, CCI + DEX25, CCI + DEX50, and CCI + DEX100. Fourteen days after CCI, mice that did not develop a depressive phenotype were excluded through sucrose preference test (SPT), forced swimming test (FST), paw thermal withdrawal latency (PTWL), and serum corticosterone (CORT). Subsequently, mice in the sham group were administered 0.1 mL/10 g NS once daily. However, mice in the CCI subgroups were administered NS (0.1 mL/10 g), DEX (6.25 µg/kg), DEX (12.5 µg/kg), DEX (25 µg/kg), DEX (50 µg/kg), and DEX (100 µg/kg) intraperitoneally once daily for 1 week, respectively. Afterward, bromodeoxyuridine (BrdU) was injected intraperitoneally once daily as well for 3 consecutive days before sampling, following BrdU- and doublecortex (DCX)-positive cell detection in the hippocampus through immunofluorescence. RESULTS: The success rate of the chronic pain-depression (CPD) model was 62.5%. As observed, DEX dose-dependently affected sucrose preferences during the SPT and immobility time during FST. Results also showed that 25 µg/kg DEX had the best promotion effect during increased sucrose preference and reduced immobility time. Moreover, although DEX improved PTWL and serum CORT, no improvement over the DEX 25 µg/kg treatment was observed. Compared to the sham group, the percentage of BrdU+ and DCX+ cells was also significantly lower in the CCI + NS group. Besides, DEX dose-dependently affected cell proliferation and neuronal differentiation. Additionally, the percentage of BrdU+ and DCX+ cells in the dentate gyrus (DG) region of the hippocampus was highest in the CCI + DEX25 group. CONCLUSION: Therefore, DEX dose-dependently alleviates depression induced by chronic pain through neurogenesis promotion in the DG region of the hippocampus.
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Dor Crônica , Dexmedetomidina , Neuralgia , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Bromodesoxiuridina/farmacologia , Corticosterona , Depressão/tratamento farmacológico , Dexmedetomidina/farmacologia , Dexmedetomidina/uso terapêutico , Hipocampo , Camundongos , Neuralgia/tratamento farmacológico , Neurogênese , Sacarose/farmacologiaRESUMO
Neuroinflammation is the main pathological mechanism of cognitive dysfunction caused by neurodegenerative diseases, and effective preventive and therapeutic measures are not available. We predicted the key targets of gastrodin's effects upon neuroinflammation through Network Pharmacology and molecular docking. Then the predicted targets were used to study how gastrodin affected cognitive dysfunction triggered by lipopolysaccharide-induced neuroinflammation in rats and its mechanisms. Three-month-old male rats were intraperitoneally injected with lipopolysaccharide for 3 days (d), 7 d and 14 d respectively. Gastrodin improved learning and memory ability of rats with neuroinflammation. Lipopolysaccharide enhanced the levels of pro-inflammatory cytokines, such as TNF-α, IL-1ß and IL-6, in rat hippocampus, which could be reversed by gastrodin. Gastrodin also inhibited the activation of microglia. Our findings suggested that gastrodin exerted neuroprotective effects in rats with neuroinflammation by impacting the TLR4-NF-kB-NLRP3 pathway. Therefore, gastrodin may be a potential therapeutic agent for neuroinflammation-induced cognitive dysfunction.
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Disfunção Cognitiva , Inflamassomos , Masculino , Ratos , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR , Lipopolissacarídeos/toxicidade , Simulação de Acoplamento Molecular , Doenças Neuroinflamatórias , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologiaRESUMO
In this medical report, we successfully implemented anesthesia management for an infant with congenital heart disease undergoing congenital diaphragmatic hernia (CDH) repair. Left-sided CDH was diagnosed on a postnatal chest X-ray on day 1 of her life. The child was complicated with congenital heart diseases and pulmonary hypertension and showed severe dyspnea immediately after birth. Thoracoscopic CDH repair puts forward high requirements for anesthesia. Neonatal CDH combined with congenital heart disease brings more challenges to anesthesia. For high-risk premature neonates, anesthesia selections are essential, as those factors directly affect the prognosis. We report the application of S-ketamine as an anesthetic in this kind of operation for the first time. The postoperative recovery was uneventful. This case report reviews anesthesia management of critical CDH neonates, hoping to provide information to healthcare professionals unfamiliar with the treatment of this kind of patient.
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Anestesia , Cardiopatias Congênitas , Hérnias Diafragmáticas Congênitas , Hipertensão Pulmonar , Criança , Feminino , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/cirurgia , Hérnias Diafragmáticas Congênitas/complicações , Hérnias Diafragmáticas Congênitas/cirurgia , Humanos , Lactente , Recém-Nascido , Estudos RetrospectivosRESUMO
BACKGROUND: Surgical resection remains the best option for long-term survival in colorectal cancer (CRC); however, surgery can lead to tumor cell release into the circulation. Previous studies have also shown that surgery can affect cancer cell growth. The role of perioperative factors influencing long-term survival in patients presenting for CRC surgery remains to be investigated. METHODS: This retrospective single-center cohort study was conducted to collect the clinical data of patients who underwent elective laparoscopic resection for CRC from January 2014 to December 2015, namely clinical manifestations, pathological results, and perioperative characteristics. Survival was estimated using the Kaplan-Meier log-rank test. Univariable and multivariable Cox regression models were used to compare hazard ratios (HR) for death. RESULTS: A total of 234 patients were eligible for analysis. In the multivariable Cox model, tumor-node-metastasis (TNM) stage (stage IV: HR 30.63, 95% confidence interval (CI): 3.85-243.65; P = 0.001), lymphovascular invasion (yes: HR 2.07, 95% CI 1.09-3.92; P = 0.027), inhalational anesthesia with isoflurane (HR 1.96, 95% CI 1.19-3.21; P = 0.008), and Klintrup-Makinen (KM) inflammatory cell infiltration grade (low-grade inflammation: HR 2.03, 95% CI 1.20-3.43; P = 0.008) were independent risk factors affecting 5-year overall survival after laparoscopic resection for CRC. CONCLUSIONS: TNM stage, lymphovascular invasion, isoflurane, and KM grade were independent risk factors affecting CRC prognosis. Sevoflurane and high-grade inflammation may be associated with improved survival in CRC patients undergoing resection.
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Neoplasias Colorretais , Estudos de Coortes , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Humanos , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Fatores de RiscoRESUMO
Stellate ganglion block (SGB) has been applied in clinic for almost a century as a therapeutic procedure to alleviate pain-related syndromes and vascular deficits in the upper extremities. A great number of causative side effects and complications due to technological insufficiency and anatomical variations called for the popularity of ultrasound-guided SGB which has made tremendous contribution for clinical diagnosis and therapy, primarily in postoperative pain and cardiac and vascular disorders. This work was aimed at systematically summarizing the current clinical application of ultrasound-guided SGB and putting forward the potential prospective application in future. By searching ultrasound-guided SGB-related works on PubMed database, we mainly elucidated the analgesic effect of preoperative SGB in patients undergoing surgical procedures and substantial reduction in patients with ventricular arrhythmias. The volume of local anesthetics used in ultrasound-guided SGB has been diminished in the recent few years' investigations and successful operation of ultrasound-guided SGB could be achieved with minimal safe volume of local anesthetics. This invasive and safe procedure shows vast potential for future development in clinical treatment for autonomic nervous system and autoimmune disorders. We also put forward hypothesis that ultrasound-guided SGB could be applied combined with controlled hypotension to reduce the intraoperative complications in orthopedic surgery such as insufficiency of cerebral blood flow and reflexive tachycardia. Thus, it is of vital essence to improve the professional skills of physicians for the high rate of success and explore more effective measures which could enhance therapeutic effects when combined with ultrasound-guided SGB in alleviating misery of patients.
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Dor Pós-Operatória , Gânglio Estrelado , Arritmias Cardíacas , Humanos , Dor Pós-Operatória/terapia , Estudos Prospectivos , Gânglio Estrelado/diagnóstico por imagem , Ultrassonografia de IntervençãoRESUMO
This report describes the intraoperative course of endoscopic thyroidectomy by oral vestibular approach in a female patient. This operation is new, and its perioperative management is not yet mature. In this case, the surgery resulted in trachea injury that could not be detected easily. As a result, the patient suddenly developed acute dyspnea and circulatory disorder. This procedure requires caution in surgical execution and anesthesia management.
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Endoscopia/efeitos adversos , Complicações Intraoperatórias , Tireoidectomia/efeitos adversos , Traqueia/lesões , Doenças da Traqueia/etiologia , Feminino , Humanos , Pessoa de Meia-Idade , Doenças da Glândula Tireoide/cirurgia , Traqueia/diagnóstico por imagem , Doenças da Traqueia/diagnósticoRESUMO
BACKGROUND: The video laryngoscope is recommended for intubating difficult airways. The present study aimed to determine whether the video laryngoscope can further improve intubation success rates compared with the direct laryngoscope in patients with non-difficult airways. METHODS: In total, 360 patients scheduled for elective abdominal surgeries were randomly assigned to undergo intubation using either a video laryngoscope (n = 179) or a direct laryngoscope (n = 181). The following parameters were measured: mouth opening; thyromental distance; sternomental distance; shape angle of the tracheal catheter; and glottic exposure grade. RESULTS: The percentage of patients with level I-II of total glottic exposure in the video laryngoscope group was 100% versus 63.5% in the direct laryngoscope group (P < 0.001). The one-attempt success rate of intubation was 96.1% using a video laryngoscope versus 90.1% using a direct laryngoscope (P = 0.024). The intubation success rate using a video laryngoscope was 100% versus 94.5% using a direct laryngoscope (P = 0.004). Immediate oropharyngeal injury occurred in 5.1% of patients intubated using a direct laryngoscope versus 1.1% using a video laryngoscope (P = 0.033). On postoperative day 1, obvious hoarseness was exhibited by 7.9% of patients intubated using a direct laryngoscope versus 2.8% using a video laryngoscope (P = 0.035). The grade of glottic exposure and catheter shape angle were independent risk factors for tracheal intubation failure. Thyromental distance, shape angle, glottic exposure time, and surgical position were independent risk factors for postoperative complications. Thyromental distance and glottic exposure time were independent risk factors for complications lasting > 2 days. CONCLUSIONS: Intubation using a video laryngoscope yielded significantly higher intubation success rates and significantly fewer postoperative complications than direct laryngoscopy in patients with non-difficult airways. TRIAL REGISTRATION: Chinese Clinical Trial Registry. No: ChiCTR-IOR-16009023 . Prospective registration.
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Procedimentos Cirúrgicos Eletivos/métodos , Intubação Intratraqueal/métodos , Laringoscópios , Laringoscopia/métodos , Cirurgia Vídeoassistida/métodos , Adulto , Procedimentos Cirúrgicos Eletivos/instrumentação , Procedimentos Cirúrgicos Eletivos/normas , Feminino , Humanos , Intubação Intratraqueal/instrumentação , Intubação Intratraqueal/normas , Laringoscópios/normas , Laringoscopia/instrumentação , Laringoscopia/normas , Masculino , Pessoa de Meia-Idade , Cirurgia Vídeoassistida/instrumentação , Cirurgia Vídeoassistida/normasRESUMO
OBJECTIVE: To assess changes in the cognitive function and hippocampal ultrastructure of elderly rats exposed to sevoflurane. METHODS: Ault male Sprague-Dawley rats were given subcutaneous injection of D-galactose on the neck for 40 d to establish elderly models, after 9-day behavioral training. The model rats were divided into 3 groups randomly: control group with natural air, A/O group with 6 h exposure to carrier gas (2 L/min Air+2 L/min O2), and Sev group with 6 h exposure to 3.2% sevoflurane through carrier gas. Morris Water Maze and balance beam experiment were conducted on 6 rats in each group 2 h, 1 week and 4 weeks after treatments, respectively. The hippocampal tissues of the rats were rapidly dissected and prepared by glutaraldehyde fixation, ethanol dehydration, infiltration, embedding polymerization, semimembrane section localization and staining for examinations under transmission electron microscopy. The hippocampal ultrastructure such as nucleus, cytoplasm, mitochondria, endoplasmic reticulum, medullary nerve fiber, synapse and apoptotic corpuscle were observed. RESULTS: Ethology: compared with the control and A/O groups, significant reductions in the probe trial capability were found in the rats after 2 h exposure to sevoflurane, which recovered at 1 week and 4 weeks. Sevoflurane also increased the working memory escape latency 2 h and 1 week after exposure. The balance beam experiment showed that sevoflurane prolonged the staring time of rats after 2 h exposure, which recovered at 1 week and 4 weeks. Prolonged length for going through the balance beam was found consistently in the rats exposed to sevoflurane. Transmission electron microscopy: rats in the control group were found to have clear hippocampal ultrastructure, intact nuclear membrane, no edema fluid in the cytoplasm, intact mitochondria and endoplasmic reticulum, normal medullary nerve fibers, intact synaptic structure, and no apoptotic bodies in the cells. But a small amount of edema were observed in the cytoplasm of hippocampal cells in the rats exposed to sevoflurane and A/O at 2 h, which increased at 1 week. The cytoplasmic morphology of rats in the A/O group returned to normal at 4 weeks. But further increase of edema was observed in the rats 4 weeks after exposure to sevoflurane. No abnormal morphological structures or apoptotic bodies in other organelles were found. CONCLUSIONS: Sevoflurane can induce early neurocognitive impairments in elderly rats, which may be related with changes in the hippocampus ultrastructure.
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Envelhecimento , Cognição , Hipocampo/ultraestrutura , Sevoflurano/farmacologia , Animais , Hipocampo/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Etomidate is a commonly used sedative in intravenous anesthesia. The aim of this study was to compare the effects of various etomidate doses administered by continuous infusion on adrenal function in dogs under general anesthesia. METHODS: Thirty-six healthy adult male dogs were randomly divided into six groups. Sodium pentobarbital alone was administered to the control group (group C); five experimental groups (E1, E2, E3, E4, and E5) were also given etomidate at doses of 10, 15, 20, 25, and 30 µg · kg(-1) · min(-1), respectively, to maintain anesthesia. Heart rate (HR), mean arterial pressure (MAP), and bispectral index (BIS) were monitored. Serum cortisol, aldosterone, adrenaline, and noradrenaline levels were measured, and HR, MAP, and BIS values recorded, before intubation (T0), and at 1 h, 2 h, and 3 h after intubation (T1-3). RESULTS: Cortisol and aldosterone levels in groups E1-5 decreased as the doses and times of continuous infusion of etomidate increased. The cortisol level was significantly decreased compared with baseline at T3 in group E1 and at T1-3 in groups E2-5 (P < 0.05). Compared with the corresponding levels in group C, cortisol levels were significantly lower than T0 values at T3 in group E1 and at T1-3 in groups E2-5 (P < 0.05). The aldosterone level was significantly lower at T3 in group E2 and at T1-3 in groups E3-5 (P < 0.05). Significant reductions in cortisol levels at T2-3 in group E2 and at T1-3 in groups E3-5 compared with group C were also observed (P < 0.05). The plasma adrenaline and noradrenaline levels, HR, MAP, and BIS in groups E1-5 were within the normal range at the different times and with the different doses (P > 0.05). CONCLUSIONS: Cortisol and aldosterone levels decreased with time and continuous infusion of etomidate; there were no significant changes in adrenaline and noradrenaline levels, HR, MAP, and BIS in any group.
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Glândulas Suprarrenais/efeitos dos fármacos , Glândulas Suprarrenais/metabolismo , Aldosterona/sangue , Anestésicos Intravenosos/administração & dosagem , Etomidato/administração & dosagem , Hidrocortisona/sangue , Animais , Cães , Relação Dose-Resposta a Droga , Infusões Intravenosas , MasculinoRESUMO
Sevoflurane is one of the most commonly used volatile anesthetics in clinical practice and is often used in pediatric anesthesia and intraoperative maintenance. Microglia exist in the central nervous system and are innate immune cells in the central nervous system. Under external stimulation, microglia are divided into two phenotypes: proinflammatory (M1 type) and anti-inflammatory (M2 type), maintaining the stability of the central nervous system through induction, housekeeping, and defense functions. Sevoflurane can activate microglia, increase the expression of inflammatory factors through various inflammatory signaling pathways, release inflammatory mediators to cause oxidative stress, damage nerve tissues, and eventually develop into neurodegenerative diseases. In this article, the relationship between sevoflurane anesthesia and microglia inflammation expression and the occurrence of neurodegenerative diseases is reviewed as follows.
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The pathophysiological regulatory mechanisms in postoperative neurocognitive disorders (PNCDs) are intricately complex. Currently, the pathogenesis of PNCDs has not been fully elucidated. The mechanism involved may include a variety of factors, such as neuroinflammation, oxidative stress, and neuroendocrine dysregulation. Research into the gut microbiota-induced regulations on brain functions is increasingly becoming a focal point of exploration. Emerging evidence has shown that intestinal bacteria may play an essential role in maintaining the homeostasis of various physiological systems and regulating disease occurrence. Recent studies have confirmed the association of the gut-brain axis with central nervous system diseases. However, the regulatory effects of this axis in the pathogenesis of PNCDs remain unclear. Therefore, this paper intends to review the bidirectional signaling and mechanism of the gut-brain axis in PNCDs, summarize the latest research progress, and discuss the possible mechanism of intestinal bacteria affecting nervous system diseases. This review is aimed at providing a scientific reference for predicting the clinical risk of PNCD patients and identifying early diagnostic markers and prevention targets.
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Postoperative cognitive dysfunction (POCD) is a significant complication following surgery. The precise mechanisms underlying POCD remain elusive, although it is speculated that they involve central nervous system inflammation, oxidative stress and cellular apoptosis. MicroRNAs (miRNAs), a class of non-coding RNAs widely distributed in eukaryotes, have been implicated in the pathogenesis of neurodegenerative disorders and could potentially impact POCD. This review explores the association between miRNAs and POCD and provides an overview of the progress of current research on miRNAs in the pathogenesis, diagnosis, and treatment of POCD.
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MicroRNAs , Complicações Cognitivas Pós-Operatórias , Humanos , Sistema Nervoso Central , Inflamação , Estresse OxidativoRESUMO
Cognitive impairment (CI) is a mental disorder related to cognition and understanding, which is mainly categorized into mild CI and senile dementia. This disease is associated with multiple factors, such as chronic brain injury, aging, chronic systemic disease, mental state, and psychological factors. However, the pathological mechanism of CI remains unclear; it is usually associated with such underlying diseases as diabetes and hyperlipidemia. It has been demonstrated that abundant lipid metabolism indexes in the human body are closely related to CI, including total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, apolipoprotein, and so forth. As a crucial risk factor for CI, hyperlipidemia is of great significance in the occurrence and development of CI. However, the specific correlation between dyslipidemia and CI is still not fully elucidated. Besides, the efficacy of lipid-lowering drugs in the prophylaxis and treatment of CI has not been clarified. In this study, relevant advances in the influence of lipid metabolism disorders in CI will be reviewed, in an attempt to explore the effect of mediating blood lipid levels on the prophylaxis and treatment of CI, thus providing a reference for its clinical management.
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OBJECTIVE: To investigate the role of the microRNA (miRNA)-669f-5p/deoxycytidylate deaminase (Dctd) axis in sevoflurane inducing cognitive dysfunction in aged mice. METHODS: Sixty-six C57BL/6J mice were used in the experiment model and were randomly divided into the sevoflurane group and the control group. The mice in the sevoflurane group were anesthetised with 3.4% sevoflurane, whereas those in the control group were air-treated for the same period. The study was then performed using bioinformatics sequencing, as well as in vitro and in vivo validation. RESULTS: The mice in the sevoflurane group showed significant cognitive impairments in terms of a decrease in both spatial learning and memory abilities. Experimental doses of miR-669f-5p agonist exhibited no obvious effect on cognitive function following sevoflurane inhalation, but inhibiting the expression of miR-669f-5p could alleviate the impairments. Based on the results of the bioinformatics sequencing, miR-669f-5p/Dctd and the toll-like receptor (TLR) signalling pathway could be the key miRNA, gene and pathway leading to postoperative cognitive dysfunction following sevoflurane inhalation. The aged mice showed significantly increased expression of miR-669f-5p in the hippocampus following sevoflurane inhalation, and upregulating/inhibiting its expression could increase/decrease TLR expression in the hippocampus. Furthermore, miR-669f-5p could reduce the expression of the Dctd gene by binding to its 3'untranslated region. CONCLUSION: The miR-669f-5p/Dctd axis plays an important role in sevoflurane inducing cognitive dysfunction in aged mice, providing a new direction for further development of therapeutic strategies concerning the prevention and treatment of cognitive dysfunction associated with sevoflurane anaesthesia.
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General anesthesia, as a commonly used medical intervention, has been widely applied during surgical procedures to ensure rapid loss of consciousness and pain relief for patients. However, recent research suggests that general anesthesia may be associated with the occurrence of perioperative neurocognitive disorder (PND). PND is characterized by a decline in cognitive function after surgery, including impairments in attention, memory, learning, and executive functions. With the increasing trend of population aging, the burden of PND on patients and society's health and economy is becoming more evident. Currently, the clinical consensus tends to believe that peripheral inflammation is involved in the pathogenesis of PND, providing strong support for further investigating the mechanisms and prevention of PND.
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Neurodegenerative diseases (NDs), such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and motor neuron disease, are diseases characterized by neuronal damage and dysfunction. NDs are considered to be a multifactorial disease with diverse etiologies (immune, inflammatory, aging, genetic, etc.) and complex pathophysiological processes. Previous studies have found that neuroinflammation and typical microglial activation are important mechanisms of NDs, leading to neurological dysfunction and disease progression. Pyroptosis is a new mode involved in this process. As a form of programmed cell death, pyroptosis is characterized by the expansion of cells until the cell membrane bursts, resulting in the release of cell contents that activates a strong inflammatory response that promotes NDs by accelerating neuronal dysfunction and abnormal microglial activation. In this case, abnormally activated microglia release various pro-inflammatory factors, leading to the occurrence of neuroinflammation and exacerbating both microglial and neuronal pyroptosis, thus forming a vicious cycle. The recognition of the association between pyroptosis and microglia activation, as well as neuroinflammation, is of significant importance in understanding the pathogenesis of NDs and providing new targets and strategies for their prevention and treatment.
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Postoperative cognitive dysfunction (POCD) is a decrease in mental capacity that can occur days to weeks after a medical procedure and may become permanent and rarely lasts for a longer period of time. With the continuous development of research, various viewpoints in academic circles have undergone subtle changes, and the role of anesthesia depth and anesthesia type seems to be gradually weakened; Alzheimer's disease (AD) is a latent and progressive neurodegenerative disease in the elderly. The protein hypothesis and the synaptic hypothesis are well-known reasons. These changes will also lead to the occurrence of an inflammatory cascade. The exact etiology and pathogenesis need to be studied. The reasonable biological mechanism affecting brain protein deposition, neuroinflammation, and acetylcholine-like effect has a certain relationship between AD and POCD. Whereas there is still further uncertainty about the mechanism and treatment, and it is elusive whether POCD is a link in the continuous progress of AD or a separate entity, which has doubts about the diagnosis and treatment of the disease. Therefore, this review is based on the current common clinical characteristics of AD and POCD, and pathophysiological research, to search for their common points and explore the direction and new strategies for future treatment.