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Metformin Protects against Spinal Cord Injury through Inhibiting Neuronal Apoptosis and Enhancing Autophagy Mediated by Endoplasmic Reticulum Stress
Vol 38, Issue 6, 2024
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Abstract
Background: Spinal cord injury (SCI) is a spinal nerve dysfunction caused by trauma, resulting in irreversible and destructive spinal cord impairments. The present research was formulated to identify the biological functions of metformin in SCI and to probe into the intrinsic mechanisms. Methods: SCI rat models were established using Allens method and SCI rats were intraperitoneally injected with 20 or 100 mg/kg metformin. Besides, endoplasmic reticulum (ER) stress was induced in PC12 cells by administration of 1 μM thapsigargin. Then, 100 μmol/mL metformin was given to PC12 cells. Afterwards, Basso-Beattie-Bresnahan (BBB) locomotor scoring for detecting hindlimb locomotor function, hematoxylin and eosin (H&E) staining for detecting pathological changes, cell counting kit-8 (CCK-8) assay for detecting viability, TdT-mediated dUTP nick-end labeling (TUNEL) staining for detecting apoptosis, immunofluorescence and western blot for detecting autophagy and ER stress response were performed. Results: Results of in vivo experiments revealed that metformin promoted functional recovery, reduced lesion size, attenuated apoptosis in spinal cord tissues, strengthened autophagy and repressed ER stress after SCI. Additionally, in vitro experimental results evidenced that elevation of ER stress partly abolished the suppressing effects of metformin on neuronal apoptosis and reversed the promoting effects of metformin on autophagy. Conclusions: To sum up, metformin can protect against SCI by repressing neuronal apoptosis and enhancing autophagy, depending on inhibition of X-box binding protein 1 (XBP-1)-mediated ER stress.
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Copyright (c) 2024 Jiandong Li, Zhitao Shangguan, Zhenyu Wang, Wenge Liu, Gang Chen
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Medical Genetics, University of Torino Medical School, Italy

Department of Biomedical, Surgical and Dental Sciences, University of Milan, Italy