Neuroinflammation: The central enabler of postoperative cognitive dysfunction

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 167, P. 115582 - 115582

Published: Sept. 23, 2023

The proportion of advanced age patients undergoing surgical procedures is on the rise owing to advancements in and anesthesia technologies as well an overall aging population. As a complication surgery, older frequently suffer from postoperative cognitive dysfunction (POCD), which may persist for weeks, months or even longer. POCD complex pathological process involving multiple pathogenic factors, its mechanism yet unclear. Potential theories include inflammation, deposition proteins, imbalance neurotransmitters, chronic stress. identification, prevention, treatment are still exploratory stages absence standardized diagnostic criteria. Undoubtedly, comprehending development remains crucial overcoming illness. Neuroinflammation leading hypothesis component network have interactions with other mechanisms. In this review, we discuss possible ways surgery cause neuroinflammation investigate connection between POCD. Understanding these mechanisms likely ensure that future options more effective.

Language: Английский

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Esketamine is neuroprotective against traumatic brain injury through its modulation of autophagy and oxidative stress via AMPK/mTOR-dependent TFEB nuclear translocation

Experimental Neurology, Journal Year: 2023, Volume and Issue: 366, P. 114436 - 114436

Published: May 13, 2023

Language: Английский

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Effect of Esketamine on Postoperative Delirium in Patients Undergoing Cardiac Valve Replacement with Cardiopulmonary Bypass: A Randomized Controlled Trial

Anesthesia & Analgesia, Journal Year: 2024, Volume and Issue: 139(4), P. 743 - 753

Published: March 6, 2024

BACKGROUND: The aim of this study was to investigate the effects esketamine on risk postoperative delirium (POD) in adults undergoing on-pump cardiac valve surgery. METHODS: In randomized, triple-blind, controlled trial, 116 adult patients with an American Society Anesthesiologists (ASA) grade Ⅱ or Ⅲ and a New York Heart Association (NYHA) who underwent surgery cardiopulmonary bypass were included. Esketamine (0.25 mg/kg) normal saline administered intravenously before anesthesia induction. primary outcome POD, defined as positive assessment according 3-minute confusion method (CAM) for intensive care unit (CAM-ICU) twice-daily basis 7 days after Delirium duration subtype also recorded. cognitive status measured Mini-Mental State Examination at baseline, discharge, 30 postoperatively 3 months postoperatively. RESULTS: A total 112 (mean age, 52 years; 53.6% female) enrolled; 56 assigned receive esketamine, placebo. POD occurred 13 (23.2%) group 25 (44.6%) placebo (relative [RR], 0.52, 95% confidence interval [CI], 0.28–0.91; P = .018). Thirteen 24 (42.9%) had multiple episodes (RR, 0.54, CI, 0.28–0.92), vs 22 (39.3%) exhibited hyperactive subtype. CONCLUSIONS: single dose injected induction reduced incidence relatively young ASA

Language: Английский

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Repeated ( S )-ketamine administration ameliorates the spatial working memory impairment in mice with chronic pain: role of the gut microbiota–brain axis

Gut Microbes, Journal Year: 2024, Volume and Issue: 16(1)

Published: Feb. 8, 2024

Chronic pain is commonly linked with diminished working memory. This study explores the impact of anesthetic (S)-ketamine on spatial memory in a chronic constriction injury (CCI) mouse model, focusing gut microbiome. We found that multiple doses (S)-ketamine, unlike single dose, counteracted reduced spontaneous alteration percentage (%SA) Y-maze test, without affecting mechanical or thermal sensitivity. Additionally, repeated treatments improved abnormal composition microbiome (β-diversity), as indicated by fecal 16S rRNA analysis, and increased levels butyrate, key – brain axis mediator. Protein analysis showed these also corrected upregulated histone deacetylase 2 (HDAC2) downregulated brain-derived neurotrophic factor (BDNF) hippocampi CCI mice. Remarkably, microbiota transplantation from mice treated repeatedly to restored %SA hippocampal BDNF Butyrate supplementation alone %SA, BDNF, HDAC2 Furthermore, TrkB receptor antagonist ANA-12 negated beneficial effects impairment These results indicate administration ameliorates mice, mediated axis, primarily through enhancement signaling butyrate.

Language: Английский

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Esketamine alleviated cardiomyocyte ferroptosis induced by oxygen–glucose deprivation/reoxygenation (OGD/R) via cyclic GMP-AMP synthase interactor

Cytotechnology, Journal Year: 2025, Volume and Issue: 77(2)

Published: Feb. 8, 2025

Language: Английский

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cGAS-STING targeting offers novel therapeutic opportunities in neurological diseases

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: 105, P. 102691 - 102691

Published: Feb. 13, 2025

Language: Английский

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Inhibition of PINK1-Mediated Mitophagy Contributes to Postoperative Cognitive Dysfunction through Activation of Caspase-3/GSDME-Dependent Pyroptosis

ACS Chemical Neuroscience, Journal Year: 2023, Volume and Issue: 14(7), P. 1249 - 1260

Published: March 22, 2023

PTEN-induced kinase 1 (PINK1)-mediated mitophagy and caspase-1/gasdermin D canonical pyroptosis pathways have been implicated in the pathogenesis of postoperative cognitive dysfunction (POCD). However, gasdermin E (GSDME), another recently identified executioner that can be specifically cleaved by caspase-3, is highly expressed brain neurons. This study aimed to ascertain whether PINK1-dependent governs capacity through caspase-3/GSDME. Twelve month old male Sprague-Dawley rats underwent exploratory laparotomy under isoflurane anesthesia. Lipopolysaccharide (LPS)-primed SH-SY5Y cells were used mimic postsurgical neuroinflammation. For interventional study, administered with adeno-associated virus serotype 9 (AAV9)-mediated silencing Pink1 and/or caspase-3 inhibitor Ac-DEVD-CHO (Ac-DC). treated siPINK1 Ac-DC. Cognitive performance was assessed using Morris water maze test. The mitophagy- pyroptosis-related parameters determined hippocampus cells. Anesthesia/surgery LPS caused defective PINK1-mediated activation caspase-3/GSDME-dependent pyroptosis. AAV-9 mediated overexpression mitigated impairment Conversely, inhibition PINK1 aggravates POCD overactivates neuronal These abnormalities rescued Ac-DC treatment. Collectively, regulates anesthesia surgery-induced negatively affecting caspase-3/GSDME pathway, which provides a promising therapeutic target for POCD.

Language: Английский

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Safety and efficacy of low-dose esketamine in laparoscopic cholecystectomy: a prospective, double-blind randomized controlled trial

BMC Anesthesiology, Journal Year: 2024, Volume and Issue: 24(1)

Published: Feb. 1, 2024

Abstract Background Esketamine, recognized for its analgesic, sedative, and anti-inflammatory qualities, is integral in multimodal analgesia. However, the potential opioid-sparing effects of intravenous esketamine, along with impact on inflammatory responses, cognitive function during laparoscopic surgery, remain unexplored. Methods In this study, 90 patients scheduled cholecystectomy were equally randomized into three groups: a normal saline control group (NS), low-dose esketamine (LS) high-dose (HS). Subsequently, we monitored several parameters: hemodynamics, levels stress intraoperative doses sufentanil, remifentanil, propofol, 24-hour postoperative sufentanil requirements. We also evaluated alterations function, perioperative indicators, adverse reactions among groups. Results Compared to their 5 minutes prior anesthesia (T 0 ) 30 post-operation 4 ), NS exhibited more significant decrease Mean Arterial Pressure (MAP) Heart Rate (HR) at various time intervals: after skin incision 1 post-incision 2 conclusion operation 3 compared LS HS groups( P < 0.05). Furthermore, greater increase adrenaline (AD), noradrenaline (NE), endothelin (ET), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) T , so than other two 24 hours had significantly higher Montreal Cognitive Assessment (MoCA) scores those group( The groups required lower surgery ( 0.05), experienced shorter recovery times, incidences nausea, vomiting, respiratory depression Conclusion administration has been shown be safe, effective, dependable context gallbladder surgery. It capacity stabilize hemodynamic ameliorate both from hastens recovery. it fosters restoration function. Notably, when combined nalbuphine, exhibits effects, reducing outcomes. Trial registration trial registered China Clinical Trials Registry Registration Number: ChiCTR2300067596. Retrospectively (date registration: 12/01/2023).

Language: Английский

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Unraveling the role and mechanism of mitochondria in postoperative cognitive dysfunction: a narrative review

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: Nov. 12, 2024

Abstract Postoperative cognitive dysfunction (POCD) is a frequent neurological complication encountered during the perioperative period with unclear mechanisms and no effective treatments. Recent research into pathogenesis of POCD has primarily focused on neuroinflammation, oxidative stress, changes in neural synaptic plasticity neurotransmitter imbalances. Given high-energy metabolism neurons their critical dependency mitochondria, mitochondrial directly affects neuronal function. Additionally, as primary organelles generating reactive oxygen species, mitochondria are closely linked to pathological processes neuroinflammation. Surgery anesthesia can induce dysfunction, increase disrupt quality-control via various pathways, hence serving key initiators process. We conducted review role potential postoperative by consulting relevant literature from PubMed EMBASE databases spanning past 25 years. Our findings indicate that surgery inhibit respiration, thereby reducing ATP production, decreasing membrane potential, promoting fission, inducing calcium buffering abnormalities iron accumulation, inhibiting mitophagy, increasing stress. Mitochondrial damage ultimately lead impaired function, abnormal transmission, synthesis release neurotransmitters, even death, resulting dysfunction. Targeted therapies have shown positive outcomes, holding promise novel treatment for POCD.

Language: Английский

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Carnosine ameliorates postoperative cognitive dysfunction of aged rats by limiting astrocytes pyroptosis

Neurotherapeutics, Journal Year: 2024, Volume and Issue: 21(4), P. e00359 - e00359

Published: April 25, 2024

Postoperative cognitive dysfunction (POCD) is a common postoperative complication in elderly patients, and neuroinflammation key hallmark. Recent studies suggest that the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome-mediated astrocytes pyroptosis involved regulation of many neurocognitive diseases, while its role POCD remains obscure. Carnosine natural endogenous dipeptide with anti-inflammatory neuroprotective effects. To explore effect carnosine on mechanism, we established model by exploratory laparotomy 24-month-old male Sprague-Dawley rats. We found administrated notably attenuated surgery-induced NLRP3 inflammasome activation astrocytes, central inflammation, neuronal damage hippocampus aged In addition, dramatically ameliorated learning memory deficits Then vitro experiments, stimulated primary lipopolysaccharide (LPS) after pretreatment. The results also showed application alleviated inflammasome, pyroptosis, inflammatory response LPS. Taken together, these findings improves rats via inhibiting NLRP3-mediated neuroinflammation.

Language: Английский

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