Neural Regeneration Research ›› 2017, Vol. 12 ›› Issue (3): 478-485.doi: 10.4103/1673-5374.202921

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Mechanisms responsible for the inhibitory effects of epothilone B on scar formation after spinal cord injur

Wei Zhao1, Yong Chai2, Yun Hou3, Da-wei Wang1, Jian-qiang Xing1, Cheng Yang2, Qing-min Fang1   

  1. 1 Department of Spinal Surgery, Binzhou Medical University Hospital, Binzhou, Shandong Province, China; 2 Department of Anatomy, Binzhou Medical University, Yantai, Shandong Province, China; 3 Department of Histology and Embryology, Binzhou Medical University, Yantai, Shandong Province, China
  • Received:2017-02-06 Online:2017-03-15 Published:2017-03-15
  • Contact: Cheng Yang, M.D. or Qing-min Fang, yangchxn@163.com or byfqm2008@163.com.
  • Supported by:

    This work was supported by a grant from the Science and Technology Developing Program of Shandong Provincial Government of China, No. 2010GSF10254; a grant from the Medical and Health Science and Technology Plan Project of Shandong Province of China, No. 2015WS0504.

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-stabilizing 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-derived 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 treatment. 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.

Key words: 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