Esketamine at a Clinical Dose Attenuates Cerebral Ischemia/Reperfusion Injury by Inhibiting AKT Signaling Pathway to Facilitate Microglia M2 Polarization and Autophagy

Drug Design Development and Therapy, Journal Year: 2025, Volume and Issue: Volume 19, P. 369 - 387

Published: Jan. 1, 2025

This study aimed to assess the protective effect of a clinical dose esketamine on cerebral ischemia/reperfusion (I/R) injury and reveal potential mechanisms associated with microglial polarization autophagy. Experimental ischemia was induced by middle artery occlusion (MCAO) in adult rats simulated oxygen-glucose deprivation (OGD) BV-2 cells. Neurological sensorimotor function, infarct volume, histopathological changes, mitochondrial morphological apoptosis ischemic brain tissues were assessed presence or absence autophagy inducer rapamycin. The expression biomarkers related M1 M2 phenotypes determined immunofluorescence staining RT-qPCR, proteins AKT signaling pathway assayed Western blotting. Esketamine alone combined rapamycin alleviated neurological impairment, improved decreased mitigated tissue MCAO rats. Importantly, promoted phenotypic transition from both OGD-treated microglia, autophagy, inactivated signaling. Furthermore, effects enhanced addition at attenuates I/R inhibiting facilitate can provide an protection against injury. Thus, this provides new insights into neuroprotective therapeutic strategies

Language: Английский

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Role of dexmedetomidine in postoperative cognitive dysfunction and sleep improvement in aged rats by regulating the PI3K/Akt signaling pathway and its mechanism

Brain Research, Journal Year: 2025, Volume and Issue: unknown, P. 149482 - 149482

Published: Jan. 1, 2025

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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Esketamine alleviates cognitive impairment signs induced by modified electroconvulsive therapy in a depression rat model via the KLF4/p38 MAPK pathway

Journal of Affective Disorders, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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Identification of Key Genes in Esketamine’s Therapeutic Effects on Perioperative Neurocognitive Disorders via Transcriptome Sequencing

Drug Design Development and Therapy, Journal Year: 2025, Volume and Issue: Volume 19, P. 981 - 1000

Published: Feb. 1, 2025

Esketamine ameliorates propofol-induced brain damage and cognitive impairment in mice. However, the precise role underlying mechanism of esketamine perioperative neurocognitive disorders (PND) remain unclear. Therefore, this study aimed to investigate key genes associated with PND through animal modeling transcriptome sequencing. The present established a mice model administered intervention model, were divided into control, surgical group, group esketamine. Behavioral assessments conducted using Morris water maze Y paradigms, while sequencing was performed on hippocampal samples obtained from 3 groups. Differential expression analysis weighted gene co-expression network (WGCNA) data identify candidate related treating PND. Thereafter, protein-protein interaction (PPI) implemented select genes. each step subjected enrichment analysis, regulatory for constructed. findings demonstrated successful construction our indicated that exhibits certain therapeutic efficacy Ank1, Cbln4, L1cam, Gap43, Shh designated as subsequent analysis. 5 significantly enriched cholesterol biosynthesis, nonsense mediated decay (NMD), formation pool free 40s subunits, major pathway rRNA processing nucleolus cytosol, among others. Notably, miRNAs, mmu-mir-155-5p mmu-mir-1a-3p, functionally co-regulated L1cam. We uncovered identified (Ank1, Shh) contribute its effects, providing valuable reference further mechanistic studies esketamine's treatment

Language: Английский

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Longitudinal patterns of cognitive function and depression: insights from the China Health and Retirement Longitudinal Study

Journal of Global Health, Journal Year: 2025, Volume and Issue: 15

Published: Feb. 28, 2025

Abstract Background With the acceleration of population aging, cognitive impairment and depression have become serious public health challenges in countries around world. The influencing factors trajectory, dual trajectories middle-aged elderly adults not been fully studied. Methods This study used data from China Health Retirement Longitudinal Study database spanning 2011–2018. Group-based trajectory modelling group-based were employed to examine different trajectories. Restricted cubic spline multivariate logistic regression analysis elucidate relationship between sleep duration grip strength with these Mediation was conducted explore mediating roles activities daily living (ADLs) their impact on Results Trajectory identified two longitudinal patterns function scores: low high group, respectively, states cognition depression: stable state group decline group. Sleep associated has an inverted U-shaped trajectory. Grip nonlinearly above mediation effects association ADLs cognitive, 3.14, 6.14, 2.70%. While 7.21, 1.67 6.24%, respectively (P < 0.05). Conclusions only depression, trajectories, but also partially mediate will provide a basis for how intervene mental adults.

Language: Английский

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Esketamine attenuates traumatic brain injury by modulating STAT3-mediated Glycolysis and immune responses

BMC Neuroscience, Journal Year: 2025, Volume and Issue: 26(1)

Published: March 7, 2025

Secondary injury following traumatic brain (TBI) involves neuroinflammation, immune cell infiltration, and metabolic dysregulation, leading to progressive neurological damage. This study evaluates the potential of esketamine, an NMDA receptor antagonist, modulate responses, inhibit glycolysis, mitigate secondary in a TBI mouse model. Male C57BL/6J mice were subjected controlled cortical impact induce TBI. Mice treated with either alone or combined STAT3 activator colivelin, glycolysis inhibitor 2-deoxyglucose (2-DG). Neurological function, BBB permeability, macrophage polarization, glycolytic activity assessed using immunohistochemistry, flow cytometry, quantitative PCR, enzyme-linked immunosorbent assay (ELISA). Esketamine treatment significantly reduced structural tissue damage, including contusions, loss, edema, while also improving outcomes mice. Mechanistically, esketamine inhibited CD4 + T activation suppressed Th17 differentiation both vivo vitro. It promoted shift polarization from pro-inflammatory M1 phenotype anti-inflammatory M2 phenotype. Further analysis revealed that blocked activation, which turn expression genes (e.g., Hk2, Pgk1, Aldoa) essential for proliferation polarization. Co-treatment colivelin reversed esketamine's effects on STAT3-mediated 2-DG enhanced its actions. attenuates TBI-induced neuroinflammation damage by inhibiting thus reducing promoting regulatory reparative responses. These findings highlight as therapeutic option TBI, targeting modulation pathways alleviate injury. not applicable.

Language: Английский

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Chronic Kidney Disease and Cognitive Dysfunction after Cardiac Surgery

Cardiovascular Innovations and Applications, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 1, 2025

Patients with chronic kidney disease (CKD) often encounter cardiovascular complications, most commonly coronary heart disease. Although artery bypass grafting is an effective treatment for this condition, many patients experience cognitive dysfunction after cardiac surgery. The complex interactions among functional status, general anesthesia, cardiopulmonary bypass, and surgical trauma in CKD elevate the risk of neurological issues increase mortality rates Consequently, both quality life overall prognosis are significantly affected. By reviewing recent research on postoperative CKD, we sought to clarify underlying mechanisms affecting population gain theoretical insights help decrease perioperative occurrence.

Language: Английский

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Effect of esketamine on postoperative delirium and inflammatory response in patients undergoing off-pump coronary artery bypass grafting: A randomized controlled study

Journal of Cardiothoracic and Vascular Anesthesia, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

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Short-Chain Fatty Acids Alleviate Perioperative Neurocognitive Disorders Through BDNF/PI3K/Akt Pathway in Middle-Aged Rats

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: April 29, 2025

Language: Английский

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