Mechanisms underlying the promotion of functional recovery by deferoxamine after spinal cord injury in rats

• Published in: Neural regeneration research Vol. 12; no. 6; pp. 959 - 968
• Main Authors: Hao, Jian, Li, Bo, Duan, Hui-quan, Zhao, Chen-xi, Zhang, Yan, Sun, Chao, Pan, Bin, Liu, Chang, Kong, Xiao-hong, Yao, Xue, Feng, Shi-qing
• Format: Journal Article
• Language: English
• Published: India Medknow Publications and Media Pvt. Ltd 01.06.2017; Medknow Publications & Media Pvt. Ltd; Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, China; Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China%School of Medicine, Nankai University, Tianjin, China%Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China; Medknow Publications & Media Pvt Ltd; Wolters Kluwer Medknow Publications
• Subjects: Apoptosis; Care and treatment; caspase-3; Complications and side effects; Deferoxamine; Diagnosis; Dosage and administration; Free radicals; Health aspects; Laboratory animals; nerve regeneration; spinal cord injury; deferoxamine; tumor necrosis factor-α; interleukin-1β; apoptosis; iron; anti-inflammatory; glial scar; proinflammatory; rats; motor function; lipid peroxidation; neural regeneration; Proteins; Rodents; Spinal cord injuries; Tumor necrosis factor-TNF; 功能恢复; 大鼠; 机制; 白细胞介素-1β; 肿瘤坏死因子-α; 脊髓损伤; 铁离子浓度; New York; United States > US; China; spinal cord injury; proinflammatory; lipid peroxidation; interleukin-1β; apoptosis; deferoxamine; neural regeneration; glial scar; tumor necrosis factor-α; anti-inflammatory; iron; nerve regeneration; motor function; rats; apoptosis; interleukin-1β
• DOI: 10.4103/1673-5374.208591
• ISSN: 1673-5374

Deferoxamine, a clinically safe drug used for treating iron overload, also repairs spinal cord injury although the mechanism for this action remains unknown. Here, we determined whether deferoxamine was therapeutic in a rat model of spinal cord injury and explored potential mechanisms for this effect. Spinal cord injury was induced by impacting the spinal cord at the thoracic T10 vertebra level. One group of injured rats received deferoxamine, a second injured group received saline, and a third group was sham operated. Both 2 days and 2 weeks after spinal cord injury, total iron ion levels and protein expression levels of the proinflammatory cytokines tumor necrosis factor-α and interleukin-1β and the pro-apoptotic protein caspase-3 in the spinal cords of the injured deferoxamine-treated rats were significantly lower than those in the injured saline-treated group. The percentage of the area positive for glial fibrillary acidic protein immunoreactivity and the number of terminal deoxynucleotidyl transferase d UTP nick end labeling-positive cells were also significantly decreased both 2 days and 2 weeks post injury, while the number of Neu N-positive cells and the percentage of the area positive for the oligodendrocyte marker CNPase were increased in the injured deferoxamine-treated rats. At 14–56 days post injury, hind limb motor function in the deferoxamine-treated rats was superior to that in the saline-treated rats. These results suggest that deferoxamine decreases total iron ion, tumor necrosis factor-α, interleukin-1β, and caspase-3 expression levels after spinal cord injury and inhibits apoptosis and glial scar formation to promote motor function recovery.