AXONAL REGENERATION INTO CHRONICALLY DENERVATED DISTAL STUMP .1. ELECTRON-MICROSCOPE STUDIES

In this study, we have analyzed the ability of axons to regenerate int o chronically denervated peripheral nerve. As an experimental rat mode l, the proximal end of a newly transected rat tibial nerve was sutured into chronically denervated (3 months up to 16 months) common peronea l nerve. Samples for morphological studies were collected 3 and 6 week s after anastomosis of the tibial and common peroneal nerves. Our resu lts showing a distinct organization of the endoneurial matrix in the c hronically denervated distal stumps conformed with those from previous studies. Long cytoplasmic processes of endoneurial fibroblasts in clo se contact with collagen fibrils (with a diameter of 50-60 nm) surroun ded areas of thin collagen fibrils (with a diameter of 25-30 nm). Remn ants of Schwann cell columns (i.e., bands of Bungner) were situated in areas of thin collagen fibrils. After 12 months of denervation the ma jority of the Schwann cells columns were replaced by thin collagen fib rils. Successful axonal regeneration was noted in distal stumps that h ad been denervated for 14 and even 16 months. However, axonal regenera tion diminshed with prolonged denervation. The regenerating axons grew through the areas of thin collagen fibrils. The maturation and thicke ning of the regenerated axonal sprouts resulted in a decrease in areas of thin collagen fibrils. These results suggest that a chronically de nervated nerve stump has the capacity to meet regenerating axons even after 16 months of deneravation, although the progressive atrophy of S chwann cell columns impairs the liklihood of good axonal regeneration. The areas of thin collagen fibrils may act as a 'plastic' bed for suc cessful axonal regeneration, and a study of these fibrils may provide further insight into the role of the extracellular matrix during perip heral nerve regeneration.