Mechanisms responsible for the inhibitory effects of epothilone B on scar formation after spinal cord injury
Author(s): Wei Zhao, Yong Chai, Yun Hou, Da-wei Wang, Jian-qiang Xing, Cheng Yang, Qing-min Fang
Pages: 478-485
Year: 2017 Issue: 3
Journal: Neural Regeneration Research
Keyword: nerve regeneration; spinal cord injury; epothilone B; pericytes; gene expression; fibrous scar; β-tubulin; platelet-derived growth factor receptor β; neuron-glial antigen 2; fibronectin; glial fibrillary acidic protein; rats; neural regeneration;
Abstract: Scar formation after spinal cord injury is regarded as an obstacle to axonal regeneration and functional recovery. Epothilone B provides moderate microtubule stabilization and is mainly used for anti-tumor therapy. It also reduces scar tissue formation and promotes axonal regeneration after spinal cord injury. The aim of the present study was to investigate the effect and mechanism of the microtubule-stabiliz-ing reagent epothilone B in decreasing fibrotic scarring through its action on pericytes after spinal cord injury. A rat model of spinal cord injury was established via dorsal complete transection at the T10 vertebra. The rats received an intraperitoneal injection of epothilone B (0.75 mg/kg) at 1 and 15 days post-injury in the epothilone B group or normal saline in the vehicle group. Neuron-glial antigen 2, platelet-de-rived growth factor receptor β, and fibronectin protein expression were dramatically lower in the epothilone B group than in the vehicle group, but β-tubulin protein expression was greater. Glial fibrillary acidic protein at the injury site was not affected by epothilone B treat-ment. The Basso, Beattie, and Bresnahan locomotor scores were significantly higher in the epothilone B group than in the vehicle group. The results of this study demonstrated that epothilone B reduced the number of pericytes, inhibited extracellular matrix formation, and suppressed scar formation after spinal cord injury.
Pages: 478-485
Year: 2017 Issue: 3
Journal: Neural Regeneration Research
Keyword: nerve regeneration; spinal cord injury; epothilone B; pericytes; gene expression; fibrous scar; β-tubulin; platelet-derived growth factor receptor β; neuron-glial antigen 2; fibronectin; glial fibrillary acidic protein; rats; neural regeneration;
Abstract: Scar formation after spinal cord injury is regarded as an obstacle to axonal regeneration and functional recovery. Epothilone B provides moderate microtubule stabilization and is mainly used for anti-tumor therapy. It also reduces scar tissue formation and promotes axonal regeneration after spinal cord injury. The aim of the present study was to investigate the effect and mechanism of the microtubule-stabiliz-ing reagent epothilone B in decreasing fibrotic scarring through its action on pericytes after spinal cord injury. A rat model of spinal cord injury was established via dorsal complete transection at the T10 vertebra. The rats received an intraperitoneal injection of epothilone B (0.75 mg/kg) at 1 and 15 days post-injury in the epothilone B group or normal saline in the vehicle group. Neuron-glial antigen 2, platelet-de-rived growth factor receptor β, and fibronectin protein expression were dramatically lower in the epothilone B group than in the vehicle group, but β-tubulin protein expression was greater. Glial fibrillary acidic protein at the injury site was not affected by epothilone B treat-ment. The Basso, Beattie, and Bresnahan locomotor scores were significantly higher in the epothilone B group than in the vehicle group. The results of this study demonstrated that epothilone B reduced the number of pericytes, inhibited extracellular matrix formation, and suppressed scar formation after spinal cord injury.
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