Vein wrapping facilitates basic fibroblast growth factor‐induced heme oxygenase‐1 expression following chronic nerve constriction injury

Abstract

The clinical efficacy of autologous vein wrapping for recurrent compressive neuropathy has been demonstrated; however, the underlying mechanisms of this technique remain unclear. Rats were divided into chronic constriction injury (CCI) and CCI + vein wrapping (CCI + VW) groups. Mechanical allodynia was evaluated using von Frey filaments. To identify the neuroprotective factors released from veins, basic fibroblast growth factor (bFGF) mRNA expression in veins was compared to that in the sciatic nerve. The response of heme oxygenase-1 (HO-1) expression to vein wrapping was evaluated by RT-PCR and enzyme-linked immunosorbent assays. The effects of exogenous bFGF on HO-1 expression were evaluated using a sciatic nerve cell culture. Vein wrapping significantly increased the withdraw threshold levels compared to the untreated CCI group. bFGF mRNA expression in veins was higher than that in untreated sciatic nerves. HO-1 mRNA expression was induced at higher levels in sciatic nerve cells in the presence of exogenous bFGF compared to untreated control cells. HO-1 mRNA and protein expression in the sciatic nerve were also higher in the CCI + VW group compared with the CCI group. Our results suggest that vein-derived bFGF contributes to the therapeutic benefit of vein wrapping through the induction of HO-1 in the sciatic nerve. Vein wrapping is a useful technique for reducing neuropathic pain. Further understanding of the neurotrophic factors released from veins may help to optimize current procedures for treating recurrent compressive neuropathy and traumatic peripheral nerve injury, and lead to the development of new therapeutic methods using recombinant neurotrophic factors. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:898-905, 2018.

Wrapping With Basic Fibroblast Growth Factor‐Impregnated Collagen Sheet Reduces Rat Sciatic Nerve Allodynia

“…To optimize the incubation time for bFGF binding to collagen sheets, we cut insoluble type I collagen sheets procured from pigs (Nippi Research Institute of Biomatrix, Tokyo, Japan) into five 8 × 5 × 0.2 mm pieces and immersed each piece in 2 ml of 25 μg/ml bFGF solution for 15, 30, 60, or 90 min at 4°C. Following incubation, we collected the supernatants and performed direct enzyme‐linked immunosorbent assay (ELISA) to determine collagen binding based on a previously reported method . Briefly, we coated all wells of an enzyme immunoassay plate (Costar, Cambridge, MA) with 100 μl of supernatant.…”

“…Therefore, 50 µg bFGF was used for preparation of wrap material. Collagen for wrapping was prepared according to a previously reported method . Briefly, we added an insoluble type I collagen sheet procured from pigs (Nippi Research Institute of Biomatrix) to one six‐well plate for each rat and incubated the plates with PBS (PBS/CS group) or 50 μg bFGF (bFGF/CS group) at 4°C for 90 min (Fig.…”

“…mRNA expression of Hmox1 in the sciatic nerve was examined using a similar method to that reported in our previous study . For these experiments, an additional group of rats ( n = 5) that did not receive CCI surgery or treatment prior to resection of the sciatic nerve, referred to as the “normal group,” were used to determine relative gene expression levels following sciatic nerve injury.…”

“…Vein wrapping was first employed in the upper extremity to avoid scarring in peripheral nerve injury . Realization that vein tissue produced several trophic factors that play an important role in the relief of pain was another important milestone . These studies suggested that collagen materials supplemented with trophic factors may be promising for recurrent compressive neuropathy not amenable to autologous vein wrapping.…”

“…Basic fibroblast growth factor (bFGF) reportedly contributes to the proliferation of undifferentiated Schwann cells and thereby exerts neuroprotective and nerve regeneration effects . We previously reported that veins used in vein wrapping produced bFGF and relieved pain through induction of heme oxygenase‐1 (HO‐1) in chronic constriction injury (CCI) sciatic nerve injury model rats . We, therefore, endeavored to determine whether collagen sheet impregnated with bFGF could be a suitable alternative to vein wrapping.…”