AXONAL REGENERATION INTO CHRONICALLY DENERVATED DISTAL STUMP .2. ACTIVE EXPRESSION OF TYPE-I COLLAGEN MESSENGER-RNA IN EPINEURIUM

During the first 2 weeks after an injury to peripheral nerve, endoneur ial cells proliferate and express integrin beta 1 and mRNA for collage n types I and III. Clinical results for surgical repair within this ti me are clearly better than those obtained after delayed (months after original injury) surgery. The question of whether this is due to chang es in the proliferative capacity of endoneurial cells or to changes in expression of mRNA for collagen types I and III or integrin beta 1 wa s studied using rats. The left common peroneal nerve was transected an d allowed to degenerate for 3 and 6 months. After these times, the tib ial nerve of the same animals were transected, and the fresh proximal stump of the transected tibial nerve was sutured into the chronically denervated distal stump of the common peroneal nerve. At 3 and 6 weeks after the reoperation, samples were collected from the distal stump f or morphometry, immunohistochemistry and in situ hybridization. Prolif erating cells and Schwann cells were identified by immunohistochemistr y. These cells increased markedly in number during the axonal reinnerv ation. In situ hybridization revealed that in the epineurium and perin eurium, which were fibrotic, especially type I but also type III colla gen mRNA were highly expressed. The amount of type I collagen mRNA in the endoneurium seemed to increase with progressing axonal reinnervati on. Immunostaining for integrin beta 1 was negative in these distal st umps. In the present study the proliferation of endoneurial cells and expression of type I collagen mRNA in the endoneurium were similar to those found after immediate regeneration of transected peripheral nerv e. However, the failure of endoneurial fibroblasts to express the inte grin beta 1 subunit may indicate an advanced degeneration of the dener vated distal stump. Moreover, clear expression of type I and III colla gen mRNA in epineurial fibroblasts indicates scarring at the region of the transection and may play a role in prohibitting full structural r ecovery of the injured peripheral nerve.