Rk. Nath et al., ANTIBODY TO TRANSFORMING-GROWTH-FACTOR-BETA REDUCES COLLAGEN PRODUCTION IN INJURED PERIPHERAL-NERVE, Plastic and reconstructive surgery, 102(4), 1998, pp. 1100-1106
Epineurial scarring in peripheral nerve after injury inhibits normal a
xonal regeneration primarily due to fibroblast deposition of type I co
llagen. The transforming growth factor beta (TGF-beta) family is an im
portant class of signaling molecules that has been shown to stimulate
fibroblasts to produce collagen. The aim of this study was to design a
prototypic therapeutic system in which the neutralization of TGF-beta
in crushed rat sciatic nerve would decrease collagen formation. A tot
al of 45 experimental Lewis rats were used. Group 1 animals (20 rats)
sustained a unilateral crush injury to the sciatic nerve with injectio
n of phosphate buffer solution. Group 2 animals (20 rats) sustained a
unilateral crush injury to the sciatic nerve with injection of phospha
te-buffered saline and goat, anti-rat, panspecific TGF-P antibody. Gro
up 3 control animals (five rats) underwent only exposure of sciatic ne
rve with injection of antibody. All animals were killed at 14 days and
sciatic nerve specimens were harvested at that time. Slides of experi
mental tissue were processed using a S-35-labeled oligomer for procoll
agen alpha-1 mRNA, then dipped in photographic emulsion and examined b
y darkfield autoradiography. Morphometric analysis of pixel counts was
then performed. A significant reduction in to tal pixel count per hig
h-power field and in total number of fibroblasts per high-power field
was found in crushed rat sciatic nerve treated with anti-TGF-beta anti
body when compared with those treated only with phosphate-buffered sal
ine. These findings are consistent with successful reduction in procol
lagen induction after a crush injury by topical administration of bloc
king antibody against transforming growth factor beta. The concept of
growth factor blockade for therapeutic collagen reduction is attractiv
e in the context of nerve injury, and the current article provides a m
odel for future clinical application.