Author ' s response to reviews Title : Study on Salvianolic acid B in the reduction of epidural fibrosis in laminectomy rats

2 Background: Epidural fibrosis (EF) is a common complication after laminectomy. Salvianolic acid B (Sal B) is a major bioactive component of a traditional Chinese medical agent, Salvia miltiorrhiza, which has shown anti-inflammatory, anti-fibrotic and anti-proliferative properties. Objection: The object of this study was to investigate the effect of Sal B on the prevention of epidural fibrosis in laminectomy rats. A controlled double-blinded study was conducted in sixty healthy adult Wistar rats. Methods: All rats that underwent laminectomy at the L1-L2 levels. The rats were randomly divided into 3 groups of 20: (1) Sal B treatment group; (2) Vehicle group; (3) Sham group (laminectomy without treatment). All rats were sacrificed 4 weeks post-operatively. The extent of epidural fibrosis, fibroblast proliferation and the expression of vascular endothelial growth factor (VEGF) and inflammatory factors were analyzed. Results: The recovery of all rats was uneventful. In the laminectomy sites treated with Sal B, the dura mater showed no adhesion. Collagen deposition was significantly lower in the Sal B group than the other two groups. In addition, both fibroblast and inflammatory cell counting in the laminectomy sites treated with Sal B showed better grades than the other two groups. The expression of VEGF and inflammatory factors in operative sites also suggested better results in the Sal B group than the other two groups. Conclusions: Sal B inhibits fibroblast proliferation, blood vessel regeneration, and inflammatory factor expression. Thus, Sal B is able to prevent epidural scar adhesion in post-laminectomy rats. INTRODUCTION Background 3 a. Failed back surgery syndrome (FBSS) is gaining attention from both lumbar surgeons and lumbar laminectomy patients. FBSS occurs in 8-40% of patients who undergo lumbar disc surgery [1]. Recurrent persistent low back pain and chronic nerve radicular are the main characteristics for FBSS [2]. Epidural fibrosis (EF) is widely accepted to be the main contributor to FBSS [3-5]. In the present research employing laminectomy rats to simulate post lumbar surgery patient, the efficacy of Sal B in the prevention of EF was evaluated. b. The laminectomy rat model applied in the present study was reported in several previous researches [4-5]. It is widely accepted by researchers all over the world [6-8]. In summary, the surgery was performed under sterile conditions with basic surgical tools. All the rats were numbered individually after being restrained on a warm pad in the prone position. The fur of each rat was shaved around L1 and L2 and the exposed skin was sterilized. After that L1-L2 total laminectomy was performed with a micro-rongeur. Close attention was paid not to traumatize the dura and the nerve roots. After complete hemostasis with saline, the wound site was surgically closed. Objectives 4 1. Sal B can inhibit fibroblast proliferation, blood vessel regeneration, and inflammatory factor expression. 2. Sal B is able to prevent epidural scar adhesion in post-laminectomy rats. METHODS Ethical statement 5 The present research was performed in compliance with the principles of International Laboratory Animal Care and with the European Communities Council Directive