Vein Wrapping Facilitated Basic Fibroblast Growth Factor-induced Heme Oxygenase-1 Expression in a Rat Chronic Constriction Injury Model

Abstract

There is no financial information to disclose. Autologous vein wrapping is effective for treating recurrent compressive neuropathy and traumatic peripheral nerve injury. The mechanisms governing the effectiveness of vein wrapping are yet to be elucidated. Eight-week-old Wistar rats (n = 115) were randomly divided into chronic constriction injury (CCI) and CCI + vein wrapping (CCI+VW) groups. To assess mechanical allodynia, paw withdrawal threshold was measured using von Frey filaments. Vein-derived neuroprotective factors were determined by comparing basic fibroblast growth factor (bFGF) expression levels in veins and the sciatic nerve using real-time PCR (RT-PCR) analysis. The effects of exogenous bFGF on heme oxygenase-1 (HO-1) expression were examined by sciatic nerve culture. The effect of vein wrapping on HO-1 expression was assessed using RT-PCR and enzyme-linked immunosorbent assays. In addition, the localization of bFGF and HO-1 in veins and the sciatic nerve, respectively, was examined by immunohistochemistry. Rats with vein wrapping exhibited a significant increase in withdrawal thresholds compared to untreated controls (P < 0.05). bFGF mRNA levels were higher in veins compared to untreated sciatic nerves (P < 0.05). Moreover, bFGF immunoreactivity was predominantly detected in the tunica media and tunica adventitia. Exogenous bFGF enhanced HO-1 mRNA levels in sciatic nerve cells compared to untreated controls. Further, sciatic nerves of rats in the CCI+VW group had increased HO-1 mRNA and protein levels compared with those from the CCI control group. Immunohistochemical analysis revealed that HO-1 was localized to sciatic nerve bundles in the CCI+VW group. Our results suggest that bFGF released by veins can induce HO-1 expression in sciatic nerves, which may constitute the underlying mechanism for the therapeutic benefits of vein wrapping.