Effect of microglial Pd1 on glial scar formation after spinal cord injury in mice DOI Creative Commons

Yunyun Cai,

Zhihao Lin, Xin Shen

et al.

Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108489 - 108489

Published: April 1, 2025

The crosstalk between microglia and astrocytes following spinal cord injury (SCI) greatly decides the prognosis. However, a comprehensive understanding of molecular mechanisms by which regulate astrocytic activity post-SCI is lacking. Programmed cell death protein 1 (Pdcd1, Pd1) plays crucial role in modulating immune responses exerting suppressive effects on peripheral cells within central nervous system (CNS). Previous studies have shown involvement Pd1 pathogenesis SCI; however, microglial activation glial scar formation remains elusive. Here, we demonstrated that pharmacological depletion using minocycline decreased expression TNF-α IL-6 while concurrently increasing IL-10 SCI, thereby facilitating motor function recovery mice. We observed an increase injured after with precise localization microglia. Based knockout (KO) mice, further revealed deficiency disrupted formation, leading to increased inflammation, impeded nerve regeneration, enlarged tissue damage, compromised functional SCI. In vitro study showed siRNA-mediated inhibition followed lipopolysaccharide (LPS) treatment significantly inhibited astrocyte migration upregulated secretion CXCL9 from microglia, indicating regulates through inflammatory microenvironment. Our gains new mechanistic insight into how fate SCI promotes as promising therapeutic target for

Language: Английский

Ginsenoside Rg1 Regulates Immune Microenvironment and Neurological Recovery After Spinal Cord Injury Through MYCBP2 Delivery via Neuronal Cell‐Derived Extracellular Vesicles DOI Creative Commons

Yuluo Rong,

Jiaxing Wang, Tao Hu

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(31)

Published: June 19, 2024

Abstract Spinal cord injury (SCI) is a severe neurological condition that frequently leads to significant sensory, motor, and autonomic dysfunction. This study sought delineate the potential mechanistic underpinnings of extracellular vesicles (EVs) derived from ginsenoside Rg1‐pretreated neuronal cells (Rg1‐EVs) in ameliorating SCI. These results demonstrated treatment with Rg1‐EVs substantially improved motor function spinal cord‐injured mice. enhance microglial polarization toward M2 phenotype repressed oxidative stress, thereby altering immune responses decreasing inflammatory cytokine secretion. Moreover, diminish reactive oxygen species accumulation enhanced neural tissue repair by regulating mitochondrial function. Proteomic profiling highlighted enrichment MYCBP2 Rg1‐EVs, functional assays confirmed knockdown counteracted beneficial effects vitro vivo. Mechanistically, implicated ubiquitination degradation S100A9, promoting M2‐phenotype reducing stress. Overall, these findings substantiated pivotal role protection recovery following SCI through MYCBP2‐mediated S100A9. research offers novel insights into therapeutic strategies against supports clinical Rg1‐EVs.

Language: Английский

Citations

5
Recent advances in delivery systems of ginsenosides for oral diseases DOI
Yuqing Gu, Ze Li, Shu Zhou

et al.

Phytomedicine, Journal Year: 2025, Volume and Issue: unknown, P. 156422 - 156422

Published: Jan. 1, 2025

Language: Английский

Citations

0
Neurological Emergency Treatment Strategy: A Neuron-Targeted Regulation System for Reactive Oxygen Species Metabolism through Ferroptosis Modulation DOI

Yibo Ying,

Xiong Cai,

Peng Dai

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Spinal cord injury (SCI) represents a significant clinical challenge. Following SCI, the implementation of protective measures for neurons is critically important. Current applications hormone pulse therapy exhibit variable efficacy and considerable side effects, highlighting an urgent need therapeutic strategies. This study investigates pathological conditions ischemia hypoxia in SCI region, complemented by early transcriptome sequencing postinjury. Our findings suggest that targeting ferroptosis pivotal neuroprotection following SCI. Aiming at cascade effect mitochondrial damage leading to reactive oxygen species (ROS) production, along with extensive ROS-mediated lysosomal during signaling, we developed liposome-based system regulating iron metabolism─DTLS@CAT. innovative liposome designed specifically target neuronal mitochondria, effectively eliminate mitoROS, modulate complex interactions among metabolism, lysosomes, ROS facilitate recovery from

Language: Английский

Citations

0
Systematic Review and Network Meta‐Analysis of the Effects of Plant Extracts on Cognitive Function and Quality of Life in Stroke Patients DOI Open Access

Ji Li,

Jingfen Jin,

Yifeng Cheng

et al.

Phytotherapy Research, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

ABSTRACT In recent years, numerous researchers have focused on plant extracts derived from traditional medicines to treat stroke, as these may improve patients' cognitive function and quality of life. This study aims evaluate the effects nine distinct ( Ginkgo biloba extract, Ginsenosides, Berberine, St. John's Wort Resveratrol, Gastrodin, Crocus sativus L., Moringa oleifera Seed Panax Notoginseng Saponins) life in stroke patients. seeks conduct a network meta‐analysis assess impact Researchers systematically searched Embase, PubMed, Cochrane Library, Web Science databases database inception through October 2024 for randomized controlled trials (RCTs) exclusively(no language restrictions). The selected studies were evaluated methodological via bias risk assessment tool, data analysis software was used analyze accordingly. primary outcome measures included following scales: National Institute Health Stroke Scale (NIHSS), Modified Rankin (mRS), Activities Daily Living (ADLs), Barthel Index (BI), Montreal Cognitive Assessment (MOCA), Mini‐Mental State Examination (MMSE). Treatment ranked based probability values surface under cumulative ranking curve (SUCRA). Moreover, cluster applied six scales that reflect After screening, 48 eligible included, covering 6599 patients evaluating different extract treatments. Specifically, results 33 NIHSS score, 10 mRS 11 ADL BI MMSE eight MOCA score. Findings indicate (SUCRA 71.2%) most effective reducing scores, Berberine 84.1%) 99.1%) showed highest efficacy enhancing scores. Ginsenosides improving 74.7%), 93%), 79.7%) NMA indicates that, compared placebo, can enhance provides valuable insights into using treatment, potentially guiding clinical practice, but there are some unavoidable limitations our study, including heterogeneity, differences extraction methods extracts, lack consideration social support systems dose effects. Future longer follow‐up, larger samples, more methodologically rigorous recommended clearly establish dosages

Language: Английский

Citations

0
Effect of microglial Pd1 on glial scar formation after spinal cord injury in mice DOI Creative Commons

Yunyun Cai,

Zhihao Lin, Xin Shen

et al.

Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108489 - 108489

Published: April 1, 2025

The crosstalk between microglia and astrocytes following spinal cord injury (SCI) greatly decides the prognosis. However, a comprehensive understanding of molecular mechanisms by which regulate astrocytic activity post-SCI is lacking. Programmed cell death protein 1 (Pdcd1, Pd1) plays crucial role in modulating immune responses exerting suppressive effects on peripheral cells within central nervous system (CNS). Previous studies have shown involvement Pd1 pathogenesis SCI; however, microglial activation glial scar formation remains elusive. Here, we demonstrated that pharmacological depletion using minocycline decreased expression TNF-α IL-6 while concurrently increasing IL-10 SCI, thereby facilitating motor function recovery mice. We observed an increase injured after with precise localization microglia. Based knockout (KO) mice, further revealed deficiency disrupted formation, leading to increased inflammation, impeded nerve regeneration, enlarged tissue damage, compromised functional SCI. In vitro study showed siRNA-mediated inhibition followed lipopolysaccharide (LPS) treatment significantly inhibited astrocyte migration upregulated secretion CXCL9 from microglia, indicating regulates through inflammatory microenvironment. Our gains new mechanistic insight into how fate SCI promotes as promising therapeutic target for

Language: Английский

Citations

0