EFFECTS OF THROMBIN AND PROTEASE NEXIN-1 ON PERIPHERAL-NERVE REGENERATION

Thrombin and serine protease inhibitors such as protease nexin-1 (PN-1 ) have been implicated in neurite outgrowth activity. We compared rat sciatic nerve regeneration in 10-mm silicone tubes, bridging an 8-mm n erve gap, that were prefilled with thrombin (1.5 IU) and PN-1 (50 mu g /mL or 1 mg/mL) to those filled with saline solution (control). Neural regeneration and fibrinoid matrix progression (deposition of extracel lular matrix) were analyzed at 1, 4, 17, and 21 days after silicone tu be implantation. At 1 and 4 days after implantation, thrombin reduced fibrinoid matrix length propagation from both the proximal and distal transected nerve stumps, but PN-1 and saline did not interfere with ma trix progression (p <.05). Seventeen days after implantation, the numb er of silicone tubes containing myelinated neuronal regenerates at the mid-tube region was 1 of 6 for thrombin, 6 of 9 for PN-1, and 6 of 10 for saline solution. Twenty-one days after implantation, 11 of 11 tub es with saline solution, 9 of 11 with PN-1 at 1 mg/mL, and 7 of 9 with PN-1 at 50 mu g/mL had myelinated neural regenerates in the mid-silic one tube region, while only 2 of 9 thrombin-containing silicone tubes contained myelinated axons. There was no statistically significant dif ference in myelinated neurite regenerates at 17 and 21 days after impl antation among silicone tubes prefilled with saline solution and PN-1 (50 mu g/mL or 1 mg/mL). Thrombin interfered with matrix progression a nd significantly reduced the number of myelinated neurite regenerates (p =.01). The PN-1 and saline solutions did not inhibit matrix progres sion or affect the number of myelinated axonal regenerates (p =.92).