Enhanced peripheral nerve regeneration by acidic fibroblast growth factor

Abstract

Transection of peripheral nerves may cause permanent denervation with paralysis and disability in humans and represents a challenging problem in microsurgery. Physiologic repair at increasing intervals after the acute phase of injury results in progressively worse recovery, emphasizing the importance of rapid and timely reinnervation to optimize endorgan viability. Despite recent advances in microsurgical techniques, imperfect reinnervation results in partial return of neuromuscular function, even in the mildest neuropraxias. Axonal repair of mature neurons involves a complex interaction of molecular events, suggesting that the presence of specific neuronotropic factors might enhance the regeneration process. Recombinant human fibroblast growth factor (FGF-1) has been shown to induce both rapid angiogenesis and neurogenesis through a synthetic conduit across a 15-mm surgical gap in the peripheral nerve of the rat. Evidence of newly formed neural structures was confirmed postoperatively by histological examination in a temporal fashion over a 24-week interval. Functional motor recovery of regenerated nerves was evaluated by determining the amplitude and latency of compound muscle action potentials in treated animals. Electrophysiology studies demonstrated consistent return of motor function in 43 and 57% of animals harboring an FGF-1 conduit at 8- and 24-week intervals, respectively. None of the control animals exhibited restoration of motor function. Collectively, these data suggest that FGF may serve as an important mediator of controlled growth during peripheral nerve regeneration.