Erythropoietin-Induced Autophagy Protects Against Spinal Cord Injury and Improves Neurological Function via the Extracel
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Erythropoietin-Induced Autophagy Protects Against Spinal Cord Injury and Improves Neurological Function via the Extracellular-Regulated Protein Kinase Signaling Pathway Lin Zhong 1,2 & Hui Zhang 1 & Zheng-Fei Ding 1 & Jian Li 3,4 & Jin-Wei Lv 3,4 & Zheng-Jun Pan 2 & De-Xiang Xu 3,4 & Zong-Sheng Yin 1 Received: 25 February 2020 / Accepted: 22 June 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract The objective of this study was to explore the neuroprotective molecular mechanisms of erythropoietin (EPO) in rats following spinal cord injury (SCI). First, a standard SCI model was established. After drug or saline treatment was administered, locomotor function was evaluated in rats using the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale. H&E, Nissl, and TUNEL staining were performed to assess the ratio of cavities, number of motor neurons, and apoptotic cells in the damaged area. The relative protein and mRNA expressions were examined using western blot and qRT-PCR analyses, and the inflammatory markers, axon special protein, and neuromuscular junctions (NMJs) were detected by immunofluorescence. Both doses of EPO notably improved locomotor function, but high-dose EPO was more effective than low-dose EPO. Moreover, EPO reduced the cavity ratio, cell apoptosis, and motor neuron loss in the damaged area, but enhanced the autophagy level and extracellularregulated protein kinase (ERK) activity. Treatment with an ERK inhibitor significantly prevented the effect of EPO on SCI, and an activator mimicked the benefits of EPO. Further investigation revealed that EPO promoted SCI-induced autophagy via the ERK signaling pathway. EPO activates autophagy to promote locomotor function recovery in rats with SCI via the ERK signaling pathway. Keywords Extracellular-regulated protein kinases (ERK) . Erythropoietin (EPO) . Autophagy . Spinal cord injury (SCI)
Introduction Spinal cord injury (SCI) is well known as a catastrophic disorder of the central nervous system with limited neurological functional recovery and significant impact on the quality of life and life expectancy, which causes enormous psychological and economic burdens, but there is currently no effective * De-Xiang Xu [email protected] * Zong-Sheng Yin [email protected] 1
Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, #218 Jixi Road, Hefei 230022, China
2
Department of Orthopedics, The Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China
3
Department of Toxicology, School of Public Health, Anhui Medical University, #81 Mei Shan Road, Hefei 230032, China
4
Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Hefei, China
treatment [1, 2]. The pathological process of neurological damage after SCI includes two phases: primary injury and secondary injury [3]. The primary injury is caused by a serious impact, such as traffic accidents, falls from a great height, and spinal fractures, which is impossible to be prevented. Th
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