Ultrastructural effects of betamethasone and nerve growth factor on nerve regeneration after experimental nerve injury

Peripheral nerve injuries are important health problem in the world. Injury of a peripheral nerve leads to degeneration of distal nerve stump. Several neurotrophic agents have been evaluated for their efficacy in nerve injury. Furthermore, beneficial effects of neurotrophins, neurokines and some growth factors on the peripheral nerve injury were reported. After nerve degeneration, many of neurotrophic factors such as nerve growth factor (NGF), are synthesised in tissues and delivered to the neuronal soma via retrograde transport where they exert a trophic effect. In this study, the effects of NGF and betamethasone on the rat sciatic nerve crush injury were examined by footprint analysis, light and electron microscopic, histomorphometric and biochemical methods. Fifty male Wistar rats were divided into five groups as intact, control, received NGF treatment, betamethasone treatment and NGF+betamethasone treatment. Nerve crush injury was performed on right sciatic nerve of the animals except the intact group. Immediately after injury, betamethasone was subcutenaously injected perioperative zone to the betamethasone and NGF+betametasone treatment groups three times during the first day. NGF-ß was subcutenaously injected perioperative zone to the NGF and NGF+betamethasone groups for 14 days. Footprint analysis was made on 7, 14, 21, 28 and 35 days following the operation. After 6 weeks, sciatic nerve tissue samples were obtained and the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) activity were measured. In addition, light and electron microscopic and histomorphometric evaluations were carried out. The structures of nerve fiber were seen normal in intact group. Most of the nerve fibers were revealed degeneration of the axon and myelin sheaths, separation of myelin lamellae and disintegration of axonal structures in control group. Additionally, numerous macrophages were encountered among the nerve fibers. Although some of these findings were also seen in NGF and betamethasone treatment groups, many of the nerve fibers were exhibited normal structures. Moreover, increase of MDA levels and decrease of SOD activities were found in control group. It was interesting that decrease of MDA levels and increase of SOD activities and significant motor functional recovery were observed in NGF+betamethasone received group. Furthermore, the number of the myelinated nerve fibers, axon diameter and myelin thickness were significantly greater in combined treatment group. Although the nerve regeneration were seen in NGF and betamethasone groups, the decrease in lipid peroxidation and increase in SOD activities and significant nerve regeneration, myelin sheath formation and motor functional recovery were observed in NGF+betamethasone treatment group. Combination of nerve regenerative effect of NGF and anti-inflammatory and/or anti-edematous effects of betamethasone could be attributed to that improvement. In conclusion, combined therapy of NGF and betamethasone can improve functional recovery such a combination may be an effective approach for treatment of peripheral nerve injury.