Epidermal Neural Crest Stem Cell Conditioned Medium Enhances Spinal Cord Injury Recovery via PI3K/AKT-Mediated Neuronal Apoptosis Suppression DOI Creative Commons
Ziqian Ma, Tao Liu, Liang Liu

et al.

Neurochemical Research, Journal Year: 2024, Volume and Issue: 49(10), P. 2854 - 2870

Published: July 18, 2024

Abstract This study aimed to assess the impact of conditioned medium from epidermal neural crest stem cells (EPI-NCSCs-CM) on functional recovery following spinal cord injury (SCI), while also exploring involvement PI3K-AKT signaling pathway in regulating neuronal apoptosis. EPI-NCSCs were isolated 10-day-old Sprague-Dawley rats and cultured for 48 h obtain EPI-NCSC-CM. SHSY-5Y subjected with H 2 O treatment induce Cell viability survival rates evaluated using CCK-8 assay calcein-AM/PI staining. SCI contusion model was established adult recovery, utilizing Basso, Beattie Bresnahan (BBB) scoring system, inclined test, footprint observation. Neurological restoration after analyzed through electrophysiological recordings. Histological analysis included hematoxylin eosin (H&E) staining Nissl evaluate tissue organization. Apoptosis oxidative stress levels assessed TUNEL ROS detection methods. Additionally, western blotting performed examine expression apoptotic markers proteins related PI3K/AKT pathway. EPI-NCSC-CM significantly facilitated histological by inhibiting apoptosis modulation Administration EPI-NCSCs-CM alleviated H2O2-induced neurotoxicity vitro. The use LY294002, a PI3K inhibitor, underscored crucial role contributes ongoing exploration molecular pathways involved (SCI) repair, focusing therapeutic potential research findings indicate that exerts neuroprotective effect suppressing activation rats. These results highlight promising as strategy SCI, emphasizing significance mediating its beneficial effects. Graphical

Language: Английский

Ischemia-reperfusion injury: molecular mechanisms and therapeutic targets DOI Creative Commons
Meng Zhang, Qian Liu, Hui Meng

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Jan. 8, 2024

Abstract Ischemia-reperfusion (I/R) injury paradoxically occurs during reperfusion following ischemia, exacerbating the initial tissue damage. The limited understanding of intricate mechanisms underlying I/R hinders development effective therapeutic interventions. Wnt signaling pathway exhibits extensive crosstalk with various other pathways, forming a network system pathways involved in injury. This review article elucidates signaling, as well complex interplay between and including Notch, phosphatidylinositol 3-kinase/protein kinase B, transforming growth factor-β, nuclear factor kappa, bone morphogenetic protein, N-methyl-D-aspartic acid receptor-Ca 2+ -Activin A, Hippo-Yes-associated toll-like receptor 4/toll-interleukine-1 domain-containing adapter-inducing interferon-β, hepatocyte factor/mesenchymal-epithelial transition factor. In particular, we delve into their respective contributions to key pathological processes, apoptosis, inflammatory response, oxidative stress, extracellular matrix remodeling, angiogenesis, cell hypertrophy, fibrosis, ferroptosis, neurogenesis, blood-brain barrier damage Our comprehensive analysis reveals that activation canonical promotes organ recovery, while non-canonical exacerbates Moreover, explore novel approaches based on these mechanistic findings, incorporating evidence from animal experiments, current standards, clinical trials. objective this is provide deeper insights roles its I/R-mediated processes dysfunction, facilitate innovative agents for

Language: Английский

Citations

175
Baicalin ameliorates neuroinflammation by targeting TLR4/MD2 complex on microglia via PI3K/AKT/NF-κB signaling pathway DOI

Yufang Lü,

Zhou Rui-ying,

Ruyi Zhu

et al.

Neuropharmacology, Journal Year: 2025, Volume and Issue: 267, P. 110296 - 110296

Published: Jan. 9, 2025

Language: Английский

Citations

2
AAV-mediated VEGFA overexpression promotes angiogenesis and recovery of locomotor function following spinal cord injury via PI3K/Akt signaling DOI Creative Commons
Xin Miao, Junqing Lin, Ang Li

et al.

Experimental Neurology, Journal Year: 2024, Volume and Issue: 375, P. 114739 - 114739

Published: Feb. 22, 2024

Spinal cord injury (SCI) is a disorder of the central nervous system resulting from various factors such as trauma, inflammation, tumors, and other etiologies. This condition leads to impairment in motor, sensory, autonomic functions below level injury. Limitations current therapeutic approaches prompt an investigation into angiogenesis through persistent local expression proangiogenic factors. Here, we investigated whether overexpression adeno-associated virus (AAV)-mediated vascular endothelial growth factor A (VEGFA) mouse SCI promoted locomotor function recovery, phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway was mechanistically involved. Three weeks before SCI, AAV-VEGFA injected at T10 induce VEGFA overexpression. Neurofunctional, histological, biochemical assessments were done determine tissue damage and/or recovery neuromuscular behavioral impairments. Daily injections PI3K/Akt inhibitor LY294002 made assess possible mechanism. dramatically improved ameliorated pathological caused by SCI. Improved motor-evoked potentials hindlimbs more spinal CD31-positive microvessels observed AAV-VEGFA-overexpressing mice. reduced PI3K Akt phosphorylation levels attenuated AAV-VEGFA-related improvements. In conclusion, sustained AAV-mediated can significantly promote ameliorate after contusion model activation signaling pathway.

Language: Английский

Citations

9
The NF-κB Pathway: a Focus on Inflammatory Responses in Spinal Cord Injury DOI
Y. Ding, Qin Chen

Molecular Neurobiology, Journal Year: 2023, Volume and Issue: 60(9), P. 5292 - 5308

Published: June 7, 2023

Language: Английский

Citations

22
Microvascular endothelial cells derived from spinal cord promote spinal cord injury repair DOI Creative Commons
Zhifeng You, Xu Gao, Xinyi Kang

et al.

Bioactive Materials, Journal Year: 2023, Volume and Issue: 29, P. 36 - 49

Published: June 28, 2023

Neural regeneration after spinal cord injury (SCI) closely relates to the microvascular endothelial cell (MEC)-mediated neurovascular unit formation. However, effects of central nerve system-derived MECs on neovascularization and neurogenesis, potential signaling involved therein, are unclear. Here, we established a primary cord-derived (SCMECs) isolation with high yield purity describe differences brain-derived (BMECs) their therapeutic SCI. Transcriptomics proteomics revealed differentially expressed genes proteins in SCMECs were angiogenesis, immunity, metabolism, adhesion molecular was only pathway enriched top 10 KEGG analysis. BMECs could be induced angiogenesis by different stiffness stimulation PEG hydrogels elastic modulus 50-1650 Pa for 50-300 BMECs, respectively. Moreover, promoted or NSC (SNSC/BNSC) proliferation, migration, differentiation at levels. At certain dose, combination NeuroRegen scaffold, showed higher effectiveness promotion vascular reconstruction. The underlying mechanism this phenomenon may through VEGF/AKT/eNOS- pathway, consequently accelerated neuronal functional recovery SCI rats compared BMECs. Our findings suggested promising role restoring vascularization neural regeneration.

Language: Английский

Citations

19
Mechanisms underlying the cell-matrixed nerve grafts repairing peripheral nerve defects DOI Creative Commons
Shanshan Wang, Hongkui Wang, Panjian Lu

et al.

Bioactive Materials, Journal Year: 2023, Volume and Issue: 31, P. 563 - 577

Published: Sept. 17, 2023

Decellularized extracellular matrix (dECM), with its distinct biological properties, has gained significant attention as a natural biomaterial. Leveraging potentials, we successfully developed three-dimensional matrix-based oriented nerve graft by encapsulating fibrous scaffold multilayered conformationally intact and biologically active human bone marrow mesenchymal stem cell-derived decellularized (hBMSC-dECM). Convincingly, the hBMSC-dECM group exhibited comparable functional recoveries to autograft postoperative week 12. In comprehensive analysis, molecular regulations in were more intricate nuanced compared group. Nevertheless, both groups displayed similar regulatory processes terms of vascularization matrix. Notably, demonstrated sustained high levels regulation axon myelin regeneration at 12, while immunomodulation returned normal after peaking 2. Collectively, our findings illustrated satisfactory construction cell-matrixed that established microenvironment conducive regeneration, elucidated patterns characteristics associated different repair modes.

Language: Английский

Citations

19
Nrf2 Signaling Pathway: Focus on Oxidative Stress in Spinal Cord Injury DOI

Chun-Lin Xiao,

Hong-Tong Lai,

Jiangjun Zhou

et al.

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 2, 2024

Language: Английский

Citations

6
The Importance of Phosphoinositide 3-Kinase in Neuroinflammation DOI Open Access
Bradley J. Wright, Samuel King, Cenk Suphioglu

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(21), P. 11638 - 11638

Published: Oct. 30, 2024

Neuroinflammation, characterised by the activation of immune cells in central nervous system (CNS), plays a dual role both protecting against and contributing to progression neurodegenerative diseases, such as Alzheimer's disease (AD) multiple sclerosis (MS). This review explores phosphoinositide 3-kinase (PI3K), key enzyme involved cellular survival, proliferation, inflammatory responses, within context neuroinflammation. Two PI3K isoforms interest, PI3Kγ PI3Kδ, are specific regulation CNS cells, microglia, astrocytes, neurons, oligodendrocytes, influencing pathways, Akt, mTOR, NF-κB, that control cytokine production, cell activation, neuroprotection. The dysregulation signalling is implicated chronic neuroinflammation, exacerbation diseases. Preclinical studies show promise targeting neuronal disorders using inhibitors, AS605240 (PI3Kγ) idelalisib (PI3Kδ), which have reduced inflammation, microglial death vivo models AD. However, clinical translation these inhibitors faces challenges, including blood-brain barrier (BBB) permeability, isoform specificity, long-term safety concerns. highlights therapeutic potential modulation neuroinflammatory identifying gaps current research, particularly need for brain-penetrating isoform-specific inhibitors. These findings underscore importance future research develop targeted therapies can effectively modulate activity provide neuroprotection disorders.

Language: Английский

Citations

6
Osteopontin Promotes Angiogenesis in the Spinal Cord and Exerts a Protective Role Against Motor Function Impairment and Neuropathic Pain after Spinal Cord Injury DOI
Yingqi Weng, Feng Lu, Ping Li

et al.

Spine, Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 8, 2024

Study Design. Basic science study using a hemi-section spinal cord injury (SCI) model. Objective. We sought to assess the effect of blocking Osteopontin (OPN) up-regulation on motor function recovery and pain behavior after SCI further investigate possible downstream target OPN in injured cord. Summary Background Data. is noncollagenous extracellular matrix protein widely expressed across different tissues. Its expression substantially increases following SCI. A previous suggested that this might contribute locomotor However, its neuroprotective potential was not fully explored, nor were underlying mechanisms. Methods. constructed mouse model analyzed at time points, particular cell distribution Then, we blocked with lentivirus delivering siRNA targeting specifically examined impairment neuropathic The mechanisms explored OPN-knockdown mice cultured vascular endothelial cells. Results. proteome revealed most dramatically increased significantly 3 weeks Suppressing via exacerbated pain. Additionally, resulted an increase growth factor (VEGF), AKT phosphorylation, angiogenesis within cord, all which curbed by reduction. Similarly, knockdown suppressed VEGF expression, migration, invasion, Conclusion. demonstrates protective influence against This phenomenon may result from pro-angiogenetic OPN, possibly due activation and/or pathways.

Language: Английский

Citations

5
Recent advances on signaling pathways and their inhibitors in spinal cord injury DOI Open Access
Yi Ding, Qin Chen

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 176, P. 116938 - 116938

Published: June 14, 2024

Spinal cord injury (SCI) is a serious and disabling central nervous system injury. Its complex pathological mechanism can lead to sensory motor dysfunction. It has been reported that signaling pathway plays key role in the process neuronal recovery of SCI. Such as PI3K/Akt, MAPK, NF-κB, Wnt/β-catenin pathways. According reports, various stimuli cytokines activate these pathways related SCI pathology, thereby participating regulation processes such inflammation response, cell apoptosis, oxidative stress, glial scar formation after Activation or inhibition relevant delay inflammatory reduce prevent formation, improve microenvironment SCI, promote neural function recovery. Based on they may be potential targets for treatment Therefore, understanding its inhibitors beneficial development therapeutic new drugs. This paper mainly summarizes pathophysiological involved pathogenesis, specific inhibitors/activators treatment. In addition, this review also discusses deficiencies defects research. hoped study provide reference future research pathogenesis theoretical basis biotherapy.

Language: Английский

Citations

5