ArticleNeural regeneration research2023
Metformin promotes angiogenesis and functional recovery in aged mice after spinal cord injury by adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway.
Article in Neural regeneration research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Metformin's therapeutic potential in spinal cord injury: a systematic review and meta-analysis on locomotor recovery, neuropathic pain alleviation, and modulation of secondary injury mechanisms.Acta neurochirurgica · 2025Pooled it
- KDM6A/MMP-3 epigenetic axis governs macrophage senescence after spinal cord injury for mediating the regenerative niche to promote neurological repair.Journal of advanced research · 2026Article
- Regional Molecular Diversity in Chronic Spinal Cord Injury.Cellular and molecular neurobiology · 2026Article
- Antidiabetic Agents as Antioxidant and Anti-Inflammatory Therapies in Neurological and Cardiovascular Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- Quercetin promotes angiogenesis and protects the blood-spinal cord barrier structure after spinal cord injury by targeting the PI3K/Akt signaling pathway.Journal of translational medicine · 2025Article
- Neuroprotective Effects of Metformin Through the Modulation of Neuroinflammation and Oxidative Stress.Cells · 2025Review
- Exploring the Effects of Metformin on the Body via the Urine Proteome.Biomolecules · 2025Article
- Metformin inhibits pathological retinal neovascularization but promotes retinal fibrosis in experimental neovascular age-related macular degeneration.Frontiers in pharmacology · 2025Article
- Contrast-Enhanced Ultrasound Imaging Detects Anatomical and Functional Changes in Rat Cervical Spine Microvasculature With Normal Aging.The journals of gerontology. Series A, Biological sciences and medical sciences · 2024Article
- Metformin prevents the onset and progression of intervertebral disc degeneration: New insights and potential mechanisms (Review).International journal of molecular medicine · 2024Review
- Recent advances in the application of gasotransmitters in spinal cord injury.Journal of nanobiotechnology · 2024Review
- Contrast-enhanced ultrasound imaging detects anatomical and functional changes in rat cervical spine microvasculature with normal aging.bioRxiv : the preprint server for biology · 2024Article
- Role of CD36 in central nervous system diseases.Neural regeneration research · 2024Review
- Metformin Improves Functional Outcomes, Activates Neural Precursor Cells, and Modulates Microglia in a Sex-Dependent Manner After Spinal Cord Injury.Stem cells translational medicine · 2023Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Treatment with metformin can lead to the recovery of pleiotropic biological activities after spinal cord injury. However, its effect on spinal cord injury in aged mice remains unclear. Considering the essential role of angiogenesis during the regeneration process, we hypothesized that metformin activates the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway in endothelial cells, thereby promoting microvascular regeneration in aged mice after spinal cord injury. In this study, we established young and aged mouse models of contusive spinal cord injury using a modified Allen method. We found that aging hindered the recovery of neurological function and the formation of blood vessels in the spinal cord. Treatment with metformin promoted spinal cord microvascular endothelial cell migration and blood vessel formation in vitro. Furthermore, intraperitoneal injection of metformin in an in vivo model promoted endothelial cell proliferation and increased the density of new blood vessels in the spinal cord, thereby improving neurological function. The role of metformin was reversed by compound C, an adenosine monophosphate-activated protein kinase inhibitor, both in vivo and in vitro, suggesting that the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway likely regulates metformin-mediated angiogenesis after spinal cord injury. These findings suggest that metformin promotes vascular regeneration in the injured spinal cord by activating the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway, thereby improving the neurological function of aged mice after spinal cord injury.
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