Expression of the gene encoding the chemorepellent semaphorin III is induced in the fibroblast component of neural scar tissue formed following injuries of adult but not neonatal CNS

This study evaluates the expression of the chemorepellent semaphorin III (D )/collapsin-1 (sema III) following lesions to the rat CNS. Scar tissue, for med after penetrating injuries to the lateral olfactory tract (LOT), cortex , perforant pathway, and spinal cord, contained numerous spindle-shaped cel ls expressing high levels of sema III mRNA. The properties of these cells w ere investigated in detail in the lesioned LOT. Most sema III mRNA-positive cells were located in the core of the scar and expressed proteins characte ristic for fibroblast-like cells. Neuropilin-1, a sema III receptor, was ex pressed in injured neurons with projections to the lesion site, in a subpop ulation of scar-associated cells and in blood vessels around the scar. In c ontrast to lesions made in the mature CNS, LOT transection in neonates did not induce sema III iii mRNA expression within cells in the lesion and was followed by vigorous axonal regeneration. The concomitant expression of sem a III and its receptor neuropilin-1 in the scar suggests that sema III/neur opilin-1-mediated mechanisms are involved in CNS scar formation. The expres sion of the secreted chemorepellent sema III following CNS injury provides the first evidence that chemorepulsive semaphorins may contribute to the in hibitory effects exerted by scars on the outgrowth of injured CNS neurites. The vigorous regrowth of injured axons in the absence of sema III followin g early neonatal lesions is consistent with this notion. The inactivation o f sema III in scar tissue by either antibody perturbation or by genetic or pharmacological intervention could be a powerful means to promote long-dist ance regeneration in the adult CNS.