NEURAL THROMBIN AND PROTEASE-NEXIN-I KINETICS AFTER MURINE PERIPHERAL-NERVE INJURY

We addressed the balance between thrombin and its serpin protease nexi n I (PNI) after sciatic nerve injury in the mouse. Prothrombin levels increased twofold 24 h after nerve crush, as measured by a specific ch romogenic assay, and peaked at day 3. Thrombin activity also increased 2-4 days after injury in distal sciatic nerve segments. Nerve RNA ana lysis using reverse transcriptase-polymerase chain reaction (RT-PCR) a ssay confirmed that prothrombin was synthesized locally. We also monit ored PNI levels in these injured nerve samples by complex formation wi th an I-125-labeled target protease and found peak activity occurring later, 6-9 days after the thrombin induction. These data indicate that nerve injury first induces the synthesis of prothrombin, which is sub sequently converted to active thrombin. Nerve crush-induced thrombin i s followed by the generation of functionally active PNI and may be dir ectly responsible for its induction. By immunocytochemistry with anti- PNI antibody, we found that activated Schwann cells were the source of induced PNI. These results support the concept that the balance betwe en serine proteases and their serpins is dysregulated during nerve inj ury and suggests a role for its reestablishment in nerve damage repair .