Effect of basic fibroblast growth factor injection on peripheral nerve injury at the watershed zone in a rat model

Purpose: Peripheral nerve injury such as inferior alveolar or lingual nerve injury following dental surgery, remains a clinical problem with no satisfactory treatment options. Nerve blood flow plays a crucial role in the recovery of traumatic nerve injury, and the longitudinal distribution of nerve blood flow along the length of peripheral nerves was not uniform. Well defined watershed areas of nerve blood flow were observed at lower-thigh level of rat sciatic and tibial nerves. Our objective was to evaluate the efficacy of epineurially-injected basic fibroblast growth factor (bFGF), a potent angiogenic and neurotrophic factor, on crush nerve injury at the watershed zone. Materials and Methods: Crush injury, by compressing a nerve for 5 min using a vascular clip, was introduced at the lower-thigh level of right sciatic nerve; the watershed zone in the longitudinal axis. Immediately after nerve compression, bFGF was administered into the epineurium approximately 3 mm proximal to the site of crush injury (bFGF group). Mechanical allodynia at the hind paw using von Frey hairs, and motor nerve conduction of sciatic-tibial nerves and sensory nerve conduction of sural nerves were assessed at 48 h, and 1, 2, 3 and 4 weeks after crush injury. Histological assessments of sciatic, tibial and sural nerves were undertaken at week 2 and 4 post-surgery. Control groups included rats with PBS injection after clipping (PBS group), clipping only (Clip group), and a sham or no surgery. Results: In bFGF group, mechanical sensation thresholds of von Frey test were significantly elevated compared to PBS and Clip groups at all time-points after crush injury. bFGF group showed a significantly faster recovery of motor nerve conduction velocity in sciatic-tibial nerves than those in PBS and Clip groups, although none of rats in bFGF, PBS and Clip groups showed a full recovery of nerve conductions at week 4 post-surgery. Histologically, sciatic and tibial nerves in bFGF group revealed a greater population of regenerating nerve fibers than in PBS and Clip groups, and the density of endoneurial microvessels was significantly greater in bFGF group than in these two groups. Conclusions: bFGF therapy is a potent candidate for treatment of traumatic nerve injury at the watershed zone of nerve blood flow along the proximal-distal extent of nerve, with a potential of enhanced nerve regeneration via angiogenic and neurotrophic factors.