FIBROBLAST GROWTH FACTOR-INDUCED MOTOR END-PLATE REGENERATION IN ATROPHIC MUSCLE

Objective: To determine whether fibroblast growth factor 1 implanted w ith viable nerve into atrophic muscle will stimulate formation of func tional, acetylcholine-producing motor end plates. Design: Twelve male Lewis rats underwent predenervation of the hamstring muscle 8 weeks be fore implantation of the nerve at a site distant from the original mot or end plate. Six animals underwent implantation of the tagged nerve e nding into atrophic muscle with 50 mu g of fibroblast growth factor 1 in a fibrin adhesive carrier (group 1). Three animals underwent implan tation with nerve, fibrin adhesive, and no fibroblast growth factor 1 (group 2), and three animals underwent implantation with fibroblast gr owth factor 1 and fibrin adhesive with no nerve (group 3). Animals wer e killed 9 weeks after implantation and nerve and muscle specimens wer e harvested. Main Outcome Measures: Histoenzymologic methods for acety lcholinesterase and silver impregnation of nerve fibers were performed 9 weeks after fibroblast growth factor l-fibrin adhesive implantation . Variables included the number of motor end plates per high-power fie ld and motor end plate length. Results: Robust axonal sprouting and fo rmation of multiple motor end plates were found arborized in serial fa shion equidistant around the implanted nerve ending. Rare extrasynapti c staining occurred. End plate lengths were significantly shorter in t he fibroblast growth factor 1-treated muscles (group 1) than in the sp ecimens without fibroblast growth factor 1 (group 2) (31.2 vs 58.5 mu m; P>.001, paired t test). The arborization of motor end plates, rare extrasynaptic staining, and shorter end plate lengths seen in group 1 were all consistent with mature motor end plates. Controls (group 3) d isplayed limited motor end plate formation and extensive extrasynaptic staining typical of denervation.Conclusions: This study presents enco uraging evidence that fibroblast growth factor 1 with fibrin adhesive carrier can facilitate the reinnervation of atrophied muscle by enhanc ing the formation or revitalization of motor end plates. Future studie s will address muscle function and use of different carrier materials.