Conditioned medium of epidermal neural crest stem cells improved functional recovery and tissue repairing after spinal cord injury by suppressing neuronal apoptosis through the PI3K/AKT signaling pathway DOI Creative Commons

Ziqian Ma,

Tao Liu, Liang Liu

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 29, 2023

Abstract Aims: This study evaluated the effects of conditioned medium from epidermal neural crest stem cells (EPI-NCSCs-CM) on functional recovery after spinal cord injury (SCI) and investigated role PI3K-AKT signaling pathway in regulating neuronal apoptosis. Methods: EPI-NCSCs were isolated 10-day-old rats cultured for 48 hours EPI-NCSCs-CM was extracted. H2O2 was used to establish apoptosis model SHSY-5Y cells. Cell viability survival rate assessed using CCK-8 assay Calcein-AM/PI staining. A SCI contusion established adult Sprague-Dawley rats. Functional Basso-Bresnahan-Beattie (BBB) scoring system, inclined test, footprint observation. Electrophysiological recording used to analyze neurological restoration SCI. Histological organization Hematoxylin-eosin (H&E) staining Nissl TUNEL ROS detection applied measure oxidative stress levels. Western blot conducted detect expression levels markers PI3K/AKT signaling-related proteins. Results: significantly promoted histological rehabilitation by suppressing through pathway. In vitro indicated that administration alleviated neurotoxicity caused H2O2 The LY294002 (a PI3K inhibitor) implied plays a vital Conclusions: presents new strategy repairing EPI-NCSCs-CM, provides evidence can inhibit

Language: Английский

Alpinetin inhibits neuroinflammation and neuronal apoptosis via targeting the JAK2/STAT3 signaling pathway in spinal cord injury DOI Creative Commons
Shining Xiao, Yu Zhang, Zihao Liu

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2023, Volume and Issue: 29(4), P. 1094 - 1108

Published: Jan. 10, 2023

Abstract Background A growing body of research shows that drug monomers from traditional Chinese herbal medicines have antineuroinflammatory and neuroprotective effects can significantly improve the recovery motor function after spinal cord injury (SCI). Here, we explore role molecular mechanisms Alpinetin on activating microglia‐mediated neuroinflammation neuronal apoptosis SCI. Methods Stimulation microglia with lipopolysaccharide (LPS) to simulate models in vitro, effect release pro‐inflammatory mediators LPS‐induced its mechanism were detected. In addition, a co‐culture system cells was constructed assess apoptosis. Finally, rat used study inflammation, apoptosis, axonal regeneration, Alpinetin. Results inhibits activity JAK2/STAT3 pathway. also reverse activated reactive oxygen species (ROS) production decrease mitochondrial membrane potential (MMP) PC12 cells. vivo inflammatory response improves function. Conclusion be treat neurodegenerative diseases is novel candidate for treatment neuroinflammation.

Language: Английский

Citations

48
ISRIB facilitates post-spinal cord injury recovery through attenuation of neuronal apoptosis and modulation of neuroinflammation DOI Creative Commons
Qingyang Li, Chi Zhang,

Enlin Qi

et al.

Journal of Orthopaedic Translation, Journal Year: 2025, Volume and Issue: 51, P. 119 - 131

Published: March 1, 2025

Neuronal apoptosis and inflammation are two critical factors that impede functional recovery post spinal cord injury (SCI). Previous studies have demonstrated the inhibitory effects of integrated stress response inhibitor (ISRIB) on neuroinflammation in brain injury. However, whether ISRIB can regulate neuron death context SCI remains elusive. We employed an oxygen-glucose deprivation/reperfusion (OGD/R) model to simulate ischemia-reperfusion utilized lipopolysaccharide (LPS) activate microglia. assessed cell viability demonstrate neuroprotective effect against death, while evaluating cytokine levels expression Arg1 iNOS elucidate regulatory role neuroinflammation. Bulk RNA-seq analysis was investigate global transcriptional changes neurons microglia induced by treatment. Additionally, we validated promoting motor sensory a mouse SCI. observed exerted suppressive data revealed exhibited regulation through P53 signaling pathway, as well modulation JAK2/STAT3 pathway. Western blotting immunofluorescence analyses reduced neuronal nuclei inhibited phosphorylation JAK2 STAT3 In addition, capacity promote locomotor function Our study confirmed ability via pathway respectively. Treatment with mice promoted neural function. This research provides new evidence options for therapeutic strategies experimental support application repair

Language: Английский

Citations

1
Crosstalk Between Cell Death and Spinal Cord Injury: Neurology and Therapy DOI
Qifeng Song, Qian Cui,

Shi Sun

et al.

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(12), P. 10271 - 10287

Published: May 7, 2024

Language: Английский

Citations

7
Aucubin mitigates the elevation of microglial aerobic glycolysis and inflammation in diabetic neuropathic pain via aldose reductase DOI
Xuejing Zheng, Hou‐Yong Yu,

Yeru Chen

et al.

World Journal of Diabetes, Journal Year: 2025, Volume and Issue: 16(5)

Published: April 24, 2025

BACKGROUND Treatment of diabetic neuropathy is often limited by side effects. Aucubin, an iridoid glycoside derived from natural plants, exhibits notable anti-inflammatory and antioxidant properties. AIM To investigate the effects aucubin on neuropathic pain (DNP) glycolysis inflammation in microglia. METHODS Streptozotocin (STZ) was used to establish a DNP animal model. Blood glucose levels body weight mice were measured following STZ administration. Paw withdrawal threshold calculated for mechanical allodynia. latency recorded thermal hyperalgesia. The open field test elevated plus maze assess locomotor activity anxiety-like behavior. Western blotting utilized analysis protein expression. Immunofluorescence staining morphometric Glycolysis ATP synthesis BV-2 cell lines detected metabolic extracellular flux analysis. SwissTargetPrediction STRING databases comprehensive screening identify potential target proteins aucubin. molecular docking between possible investigated using Auto Dock Tool. line transfected with lentiviral AKR1B1-shRNA further ascertain function AKR1B1 impact aerobic during high stimulation. RESULTS Aucubin significantly improved behavior STZ-induced restored microglial inflammation. Several public studies suggested that AKR1B1, MMP2 MMP9 are involved effect DNP. failed restore context deficiency. CONCLUSION has as therapeutic agent alleviating inhibiting expression AKR1B1.

Language: Английский

Citations

0
Mechanism of M2 macrophages modulating astrocyte polarization through the TGF-β/PI3K/Akt pathway DOI

Qi-Ming Pang,

Qian Zhang,

Xiang-Chong Wu

et al.

Immunology Letters, Journal Year: 2023, Volume and Issue: 259, P. 1 - 8

Published: May 25, 2023

Language: Английский

Citations

9
Tauroursodeoxycholic Acid Inhibited Apoptosis and Oxidative Stress in H2O2-Induced BMSC Death via Modulating the Nrf-2 Signaling Pathway: the Therapeutic Implications in a Rat Model of Spinal Cord Injury DOI Creative Commons

Jiaxian Weng,

Le Wang, Kai Wang

et al.

Molecular Neurobiology, Journal Year: 2023, Volume and Issue: 61(7), P. 3753 - 3768

Published: Nov. 28, 2023

Abstract Spinal cord injury (SCI) is a prevalent and significant to the central nervous system, resulting in severe consequences. This characterized by motor, sensory, excretory dysfunctions below affected spinal segment. Transplantation of bone marrow mesenchymal stem cells (BMSCs) has emerged as potential treatment for SCI. However, low survival well differentiation rates BMSCs within microenvironment significantly limit their therapeutic efficiency. Tauroursodeoxycholic acid (TUDCA), an active ingredient found bear bile, demonstrated its neuroprotective, antioxidant, antiapoptotic effects on Thus, present study was aimed possible benefits combining TUDCA with BMSC transplantation using animal model The results showed that enhanced viability reduced apoptosis (assessed Annexin V-FITC, TUNEL, Bax, Bcl-2, Caspase-3) oxidative stress ROS, GSH, SOD, MDA) both vitro vivo. Additionally, accelerated tissue regeneration HE, Nissl, MAP2, MBP, TUJ1, GFAP) improved functional recovery BBB score) following These were mediated via Nrf-2 signaling pathway, evidenced upregulation Nrf-2, NQO-1, HO-1 expression levels. Overall, these indicate could serve valuable adjunct therapy SCI, potentially enhancing efficacy.

Language: Английский

Citations

8
Enhancing mitophagy by ligustilide through BNIP3-LC3 interaction attenuates oxidative stress-induced neuronal apoptosis in spinal cord injury DOI Creative Commons
Hui Yao, Chaoyang Cai, Weijun Huang

et al.

International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(11), P. 4382 - 4406

Published: Jan. 1, 2024

Mitophagy selectively eliminates damaged or dysfunctional mitochondria, playing a crucial role in maintaining mitochondrial quality control. However, it remains unclear whether mitophagy can be fully activated and how evolves after SCI. Our RNA-seq analysis of animal samples from sham 1, 3, 5, 7 days post-SCI indicated that was indeed inhibited during the acute subacute early stages.

Language: Английский

Citations

3
Low frequency of repetitive trans-spinal magnetic stimulation promotes functional recovery after spinal cord injury in mice through inhibiting TGF-β1/Smad2/3 signaling pathway DOI
Guanhua Jiang,

Haiwang Song,

Xing Han

et al.

Neuroscience Letters, Journal Year: 2024, Volume and Issue: 836, P. 137890 - 137890

Published: July 1, 2024

Language: Английский

Citations

2
Attenuated memory impairment and neuroinflammation in Alzheimer’s disease by aucubin via the inhibition of ERK-FOS axis DOI Creative Commons
Cuicui Wang, Xiaolin Cui,

Zhenfang Dong

et al.

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 126, P. 111312 - 111312

Published: Dec. 4, 2023

Alzheimer's disease (AD) is a degenerative illness accompanied by cognitive and memory loss. In addition to the widely accepted, convincing amyloid cascade hypothesis, activation of glial cells neuroinflammation, especially microglia-mediated has an essential role in development progression AD. Therefore, anti-inflammatory treatment becoming promising therapeutic strategy. Aucubin (Au) natural product derived from many plants with antioxidant activities. Up now, no research been conducted investigate effects Au its neuroprotective quality on AD potential molecular mechanisms medical roles. our study, results network pharmacology revealed effect The studies vivo showed that improved behaviors, counteracted deficits, ameliorated AD-like pathological features mouse brain, e.g., deposition Aβ plaques, neuronal damage, inflammatory responses induced cell overactivation, APP/PS1 mice. transcriptome sequencing further confirmed symptoms could be reversed inhibiting ERK/FOS axis alleviate response. vitro experiments suppressed BV2 activation, inhibited phosphorylation ERK1/2 expression c-FOS, reduced LPS-induced mediator production primary astrocytes. Our study suggested exerted responses, which

Language: Английский

Citations

5
Spinal Lymphatic Dysfunction Aggravates the Recovery Process After Spinal Cord Injury DOI Creative Commons

Ruiguang Zhang,

Bowen Zheng, Jing Zhang

et al.

Neuroscience, Journal Year: 2024, Volume and Issue: 549, P. 84 - 91

Published: March 8, 2024

We aimed to evaluate the role of spinal lymphatic system in cord injury and whether it has an impact on recovery after injury. Flow cytometry was used changes number microvesicles Evans blue extravasation function system. immunofluorescence were permeability blood barrier. The edema evaluated by dry wet weight.Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay apoptosis Nuclear factor-kappa B pathway detected Western blot. Behavioral tests limb function. Microvesicles released can enter thoracic duct then through lymph around spine. After ligation duct, aggravate neuropathological manifestations potential mechanism may involve nuclear pathway.

Language: Английский

Citations

1