Effects of combining electrical stimulation with BDNF gene transfer on the regeneration of crushed rat sciatic nerve

Abstract

Various techniques have been investigated to enhance peripheral nerve regeneration including the application of low-intensity electrical stimulation (ES) and the administration of growth factors, especially brain-derived neurotrophic factor (BDNF). The purpose of this study was to investigate the effects of combining short-term (ES) and recombinant adenoviral vector-mediated BDNF (BDNF-Ad) transfer, in comparison to each sole modality, on peripheral nerve regeneration in a rat model with crush-injured sciatic nerve. Sixty male Sprague-Dawley rats (250-300g) were equally distributed into four groups; the control group, the ES group, the BDNF-Ad group, and the combination group (n = 15 each). A standard crush injury was introduced to the sciatic nerve. The control group received no treatment after injury, the ES group received 30 minutes of low-intensity ES, the BDNF-Ad group received an injection of recombinant BDNF-Ad (concentration = 10(11) pfu/μl, 3 μl/rat) after injury, and the combination group received both ES and BDNF-Ad. The rats were followed-up for 3weeks. At the end of the follow-up period, the sciatic function index (ES=-39, BDNF-Ad=-38) and number of the retrogradely labeled sensory neurons were significantly increased in the ES group and the BDNF-Ad group (ES = 326, BDNF-Ad = 264), but not in the combined treatment group, compared to the control group (SFI=-53, retrogradely labeled neurons = 229). Axonal counts were highest in the ES group (7,208 axons), axonal densities in the BDNF group (10,598 axons/mm(2)), and the myelin thickness was greater in both groups as compared to the control group. The combined treatment group showed no signs of superior recovery compared to the other groups. Both the ES and the BDNF-Ad treatments were effective techniques enhancing the sciatic nerve regeneration following a crush injury in rats. Nevertheless, the combined treatment with ES and BDNF-Ad produces neither a synergistic effect nor an improvement in this injury model.