Correlation between NGF levels in wound chamber fluid and cytological localization of NGF and NGF receptor in axotomized rat sciatic nerve.

When a silicone tube is implanted in transected rat sciatic nerve, there is plasma accumulation and formation of a fibrin cable followed by proliferation and migration of neural and nonneural cells from the nerve stumps into the cable. The wound fluid exhibited neurotrophic activity of unknown origin and nature. In this study, we analyzed the NGF level in wound fluid by a sensitive enzyme immunoassay and correlated the NGF level with the cytological localization of NGF, low affinity NGF receptor (p75NGFR), and Trk receptor in the axotomized nerve by immunohistochemistry. We demonstrated a rising NGF level in wound fluid from 490 pg/ml on Day 1 to 950 pg/ml on Day 7; the serum NGF level was 1/20 of that in the wound fluid. The infiltrating leukocytes expressed strong NGF but no p75NGFR. The proliferative fibroblasts and vascular cells exhibited a short period of NGF but no p75NGFR staining. Schwann cells in the distal segment showed a prolonged period of NGF and p75NGFR expression. No Trk receptor was demonstrated on leukocytes or non-neural cells. These findings suggest that locally synthesized NGF is mainly responsible for the neurotrophic activity in the wound chamber fluid. The NGF produced by the nonneural cells may be bound and stored in the p75NGFR in Schwann cells in the distal segment prior to the arrival of the regenerating axons.