SPATIAL PATTERN OF TYPE-I COLLAGEN EXPRESSION IN INJURED PERIPHERAL-NERVE

The authors studied the spatial expression and regulation of messenger RNA for the ai subunit of collagen type I in crushed rat sciatic nerv e to provide a basis for future therapeutic manipulation. Sciatic nerv es in 20 male or female adult Lewis rats were crushed for 60:seconds; the unharmed contralateral sciatic nerves served as controls. Twenty-o ne days after injury the experimental animals were killed and their ti ssue was harvested. The spatial expression of collagen type I was dete rmined by using in situ hybridization techniques. Quantification of fi broblast number and total signal was performed through computerized mo rphometry. Collagen upregulation was evident in epineurial and perineu rial layers, with the epineurium displaying higher activity. The cells responsible for procollagen type I production were fibroblasts. No ac tivity was seen in the endoneurium. Morphometric findings indicated th at collagen upregulation in the epineurium and perineurium occurred at both pretranscriptional and posttranslational levels when compared to controls; a paired t-test analysis confirmed statistical significance for all comparisons between injured and control tissues. Epineurial f ibroblasts are responsible for the collagen production associated with crushed peripheral nerve injury in the rat. Regulation occurs pretran scriptionally as well as posttranslationally. It is interesting to spe culate that the delivery of agents directed against collagen productio n (such as neutralizing antibodies to growth factors) into epineurial tissues proximate to the time and location of clinical nerve injury mi ght mitigate later deleterious effects of excess collagen production i n axonal regeneration.