Dexmedetomidine Alleviates Brain Ischemia/Reperfusion Injury by Regulating Metastasis-associated Lung Adenocarcinoma Transcript 1/MicroRNA-140-5p/ Nuclear Factor Erythroid-derived 2-like 2 Axis DOI

Zhigang Qin,

Younian Xu

Protein and Peptide Letters, Год журнала: 2023, Номер 31(2), С. 116 - 127

Опубликована: Дек. 12, 2023

Background: Dexmedetomidine (Dex) is widely used in perioperative anesthesia, and recent studies have reported that it protects organs from ischemia/reperfusion (I/R) injury. Objective: This study was performed to investigate the role of Dex alleviating cerebral I/R injury its regulatory effects on metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/microRNA-140-5p (miR-140-5p)/nuclear factor erythroid-derived 2-like 2 (Nrf2) axis. Methods: In vivo rat middle artery occlusion (MCAO) model vitro oxygen-glucose deprivation/re-oxygenation (OGD/R)-induced neuronal were constructed. injected into animals or culture HT22 cells observe pharmacological effects. The neurological defect, brain water content, infarct volume rats, neuron viability evaluated. levels reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) detected. Besides, MALAT1, miR-140-5p, Nrf2 expression relationships among them evaluated by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, dual-luciferase reporter assay. Results: significantly alleviated rats with MCAO promoted neurons. treatment suppressed miR-140-5p expression, but elevated MALAT1 expressions. knockdown down-regulated oxidative stress Additionally, directly targeted Nrf2, also functioned as a downstream target miRNA MALAT1. Conclusion: Dex, via regulating MALAT1/miR-140-5p/Nrf2 axis, plays neuroprotective against I/R-induced

Язык: Английский

Targeting PI3K/Akt in Cerebral Ischemia Reperfusion Injury Alleviation: From Signaling Networks to Targeted Therapy DOI
Ting Zheng,

Taotao Jiang,

Hongxiang Ma

и другие.

Molecular Neurobiology, Год журнала: 2024, Номер 61(10), С. 7930 - 7949

Опубликована: Март 5, 2024

Язык: Английский

Процитировано

17
Role of dexmedetomidine in postoperative cognitive dysfunction and sleep improvement in aged rats by regulating the PI3K/Akt signaling pathway and its mechanism DOI
Ying Kong, Xiaopeng Wang, Jun Pang

и другие.

Brain Research, Год журнала: 2025, Номер unknown, С. 149482 - 149482

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

1
Dexmedetomidine Protects the Brain: Exploring the α2AR/FAK Pathway in Post-Stroke Intestinal Barrier Repair DOI Creative Commons

Xinting Zhou,

Y -J Yang,

Zixuan Su

и другие.

Frontiers in Bioscience-Landmark, Год журнала: 2025, Номер 30(2)

Опубликована: Фев. 20, 2025

Introduction: Globally, ischemic stroke is a major cause of mortality and disability, posing significant challenge in clinical practice public health. Recent studies have reported that leads to the impairment intestinal barrier migration bacteria multiple organs. This process exacerbates neurological damage by further impairing function leading bacterial translocation. Dexmedetomidine (Dex), an α2-adrenoceptor (α2AR) agonist, has proven anti-cerebral effects, yet its effects post-stroke dysfunction remain unclear. study aimed determine whether Dex mitigates brain injury following cerebral ischemia-reperfusion. Methods: A C57BL/6J mouse model middle artery occlusion (MCAO) was used for vivo experiments, while lipopolysaccharide (LPS)-induced Caco-2 monolayers served as vitro dysfunction. Neuronal apoptosis evaluated using neuronal nuclei (NeuN) terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) double labeling. Reverse transcription-quantitative PCR (RT-qPCR) performed measure pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6. Intestinal permeability assessed histological score, serum fluorescein isothiocyanate (FITC)-dextran fluorescence, endotoxin levels. The expression levels epithelial cadherin (E-cadherin), zonula occludens-1 (ZO-1), occludin were analyzed western blot immunofluorescence. Statistical analyses included analysis variance with Tukey’s post-hoc test. Results: treatment significantly reduced infarct volume (p < 0.001) improved scores compared MCAO controls. inhibited 0.01), evidenced TUNEL-positive cells Dex-treatment mice. TNF-α, IL-1β IL-6 markedly downregulated 0.05). While increased (elevated FITC-dextran levels, p restored integrity. upregulated E-cadherin 0.05) but did not restore decreased ZO-1 MCAO. promoted repair alleviated via α2AR/focal adhesion kinase (FAK) pathway Similarly, mitigated LPS-induced restoring FAK improving Conclusions: alleviates injury, possibly through activating α2AR/FAK pathway. These findings underscore potential therapeutic strategy addressing secondary complications patient outcomes.

Язык: Английский

Процитировано

1
Combined Administration of Dexmedetomidine and Propofol Mitigates Myocardial Ischemia/Reperfusion Injury by Modulating the Akt/mTOR/Nrf2 Axis to Suppress Ferroptosis DOI
Ke Yang,

Xia Kong,

Chunmei Xie

и другие.

European Journal of Pharmacology, Год журнала: 2025, Номер unknown, С. 177599 - 177599

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

1
Nueroprotection by Anesthetics in Brain Injury Models DOI Creative Commons
Alexey D. Bocharnikov,

Е. А. Боева,

M. A. Milovanova

и другие.

General Reanimatology, Год журнала: 2024, Номер 20(2), С. 65 - 69

Опубликована: Апрель 25, 2024

The aim of the study was to compare effect sevoflurane and chloral hydrate on neurological status volume brain damage after trauma ischemia in experimental models traumatic injury (TBI) focal ischemic stroke (IS) induced by photothrombosis (PT). Materials methods . experiments were performed mongrel Wistar rats weighing 250–300 g (N=43). There 4 groups: Ischemia + Sevoflurane group (ISSEV) (N=10), Chloral (ISCH) TBI (TBISEV) (N=13), TBI+Chloral (TBICH) (N=10). Ischemic modelled using Rose Bengal (RB) dye-induced PT, mechanical force-induced concussion. Results. MRI findings indicate lower volumes (mm³) from TBISEV compared with TBICH (19±5 vs. 60±5, P<0.0001), ISSEV ISCH (9.8±1.5 21.5±2, P=0.0016). Moreover, there a significant difference between groups based protocol assessment day 14 higher scores (11.4±1.8 4.9±2.6, P<0.0001). Conclusion. Taking into account data obtained, we recommend careful choice anesthesia when modeling animals. In particular, neuroprotective should be taken PT models.

Язык: Английский

Процитировано

3
Dexmedetomidine activates mitophagy and protects against pyroptosis in oxygen-glucose deprivation/reperfusion-induced brain damage via PINK1/Parkin pathway activation DOI
Jieru Zhang,

Ruxia Li,

Liguo Wang

и другие.

Journal of Bioenergetics and Biomembranes, Год журнала: 2025, Номер unknown

Опубликована: Фев. 22, 2025

Язык: Английский

Процитировано

0
Dexmedetomidine pretreatment alleviates brain injury in middle cerebral artery occlusion (MCAO) model rats by activating PI3K/AKT/NF-κB signaling pathway DOI
Wei Gao,

Xue Lv,

Hao Li

и другие.

Journal of Toxicology and Environmental Health, Год журнала: 2025, Номер unknown, С. 1 - 11

Опубликована: Фев. 24, 2025

Cerebral ischemia-reperfusion injury (CIRI) is a prevalent clinical complication associated with reperfusion following ischemic stroke resulting in neuronal damage and cognitive impairment. Dexmedetomidine (DEX), highly selective α2-adrenoceptor agonist sedative, analgesic properties, frequently utilized as sedative anesthetic surgeries, believed to play crucial role the prognosis of patients suffering from CIRI. However, mechanism underlying DEX CIRI remains be determined. This study aimed investigate neuroprotective effects Dex rats In treatment group, (50 µg/kg) was administered intraperitoneally 30 min prior surgery. Middle cerebral artery occlusion (MCAO) used model occurred for 2 h followed by blood 24, 72, 120 or 168 h. Neurological function assessed Longa neurological score test demonstrated significantly reduced scores increased % infarct size MCAO group which blocked suggesting that might effective treating stroke. animals, 2,3,5-triphenyltetrazolium chloride (TTC) showed large marked areas infarction were diminished DEX. Using Western blot analysis, results protein expression levels TNF-α IL-6 accompanied PI3K/AKT signaling pathway. pretreatment reversed evidenced decrease elevated PI3K/AKT/NF-κB Data improved neuromotor performance functions animals consequences diminishing inflammation activation

Язык: Английский

Процитировано

0
New insights into the pharmacological mechanisms of Jinqi Jiangtang Tablets in the treatment of type 2 diabetes mellitus: A multi-omics approach combined with experimental validation DOI
Yining Gong, Xinchen Tian, Xiaoqing Ma

и другие.

Journal of Ethnopharmacology, Год журнала: 2025, Номер unknown, С. 120020 - 120020

Опубликована: Май 1, 2025

Язык: Английский

Процитировано

0
The Integration Strategy of Didang Decoction Against Cerebral Ischemia-Reperfusion Injury: Regulation of Apoptosis-Autophagy-Inflammation Network and Validation of Pi3k/Akt Pathway DOI
Zhiguang Song, Yansong Liu,

S. Dai

и другие.

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0
Leucine Reduced Blood–Brain Barrier Disruption and Infarct Size in Early Cerebral Ischemia-Reperfusion DOI Creative Commons
Oak Z., Xia Liu,

Jedrick Magsino

и другие.

Brain Sciences, Год журнала: 2023, Номер 13(10), С. 1372 - 1372

Опубликована: Сен. 26, 2023

A disruption of the blood–brain barrier (BBB) is a crucial pathophysiological change that can impact outcome stroke. Ribosomal protein S6 (S6) and kinase B (Akt) play significant roles in early cerebral ischemia-reperfusion injury. Studies have suggested branched-chain amino acids (BCAAs) may neuroprotective properties for spinal cord or brain injuries. Therefore, we conducted research to investigate if leucine, one BCAAs, could offer neuroprotection alter BBB disruption, along with its effects on phosphorylation Akt during phase ischemia-reperfusion, specifically within thrombolytic therapy time window. In rats, ten min after left middle artery occlusion (MCAO), 5 µL 20 mM L-leucine normal saline was injected into lateral ventricle. After two hours reperfusion following hour MCAO, determined transfer coefficient (Ki) 14C-α-aminoisobutyric acid assess infarct size, Akt. Ischemia-reperfusion increased Ki (+143%, p < 0.001) intra-cerebroventricular injection leucine lowered ischemic-reperfused cortex (−34%, 0.001). Leucine reduced percentage cortical (−42%, 0.0001) out total area. alone significantly both (p 0.05). However, administration had no further effect cortex. This study suggests an acute increase levels few stroke neuroprotection, possibly due being major contributing factors. did not already elevated by under current experimental conditions. Our data warrant studies neuronal survival mechanisms later stages ischemia-reperfusion.

Язык: Английский

Процитировано

8