Peripheral nerve regeneration in interleukin 6-deficient mice.

BACKGROUND: Interleukin 6 (IL-6) is a multifunctional cytokine with effects on central and peripheral neurons. OBJECTIVE: To investigate the role of IL-6 in peripheral nerve regeneration by comparing IL-6 knockout and wild-type mice in a sciatic nerve model of injury and repair. DESIGN/SUBJECTS: Forty C57/BL6 (wild-type) and 40 IL-6 knockout mice were randomly assigned to 1 of 4 groups: sham surgery, sciatic nerve crush injury, sciatic nerve transection without repair, and sciatic nerve transection with epineurial suture repair. Walking tracks were assessed preoperatively and postoperatively at 10-day intervals for 50 days by means of a previously described mouse sciatic functional index. Distal segments of the sciatic nerves were harvested at the completion of the study for histomorphometric evaluation. RESULTS: The wild-type and knockout mice that underwent sham surgery showed similarly unimpaired function (P =.64 on day 50). The IL-6 knockout mice with the crush injury demonstrated decreased function on day 10 compared with the wild-type mice (P<.01) but completely recovered by day 40 (P =.55). Both IL-6 knockout and wild-type mice that underwent nerve transection without repair failed to recover function (P =.06 on day 50). There was no statistical difference in recovery between wild-type and IL-6 knockout mice that underwent nerve transection with epineurial suture repair (P =.30 on day 50). The morphometric data showed no significant differences in distal axon count between the wild-type and knockout mice after suture repair or crush injury (P>.32). CONCLUSIONS: The absence of IL-6 does not appear to impair peripheral nerve recovery after sciatic nerve injury. Although in vitro and in vivo studies suggest a role for IL-6 in peripheral nerve physiology, this cytokine does not appear to have a substantial effect on functional recovery in a mouse sciatic nerve injury and repair model.

A longitudinal, functional study of peripheral nerve recovery in the mouse.

OBJECTIVES: To verify the validity of the recently described sciatic functional index for mice to monitor neuronal functional recovery over time using a blinded, randomized, and controlled evaluation. STUDY DESIGN: Surgery was performed on the left sciatic nerves of 62 C57/BL mice after randomly assigning them to one of four surgical groups: sham surgery, sciatic nerve crush, nerve transection without repair, and nerve transection followed by epineurial suture repair. Sciatic functional indices were measured before surgery and then after surgery at 10-day intervals for 90 days, using a previously described formula. RESULTS: Sham surgery did not affect nerve function when compared with preoperative values (P > .24). Crush surgery produced a reversible nerve injury that fully recovered after 20 days. Nerve transection without repair resulted in complete functional disability without recovery of function during the 90-day follow-up interval. When transected nerves were repaired, complete functional disability was noted at day 10, with subsequent functional recovery to 26% of function at day 30. This level of recovery persisted until the 60th postoperative day when muscle contractures resulted in progressive worsening of the index. There were statistically significant differences between the sciatic functional indices of each of the groups (P < .05). CONCLUSIONS: The previously described sciatic functional index for mice is an accurate indicator of the level of sciatic neuronal function during recovery. This index represents a method of evaluating neuronal function that may provide a better reflection of the recovery parameters that are important in clinical situations. The sciatic functional index will allow for study of sciatic nerve functional recovery in genetically engineered transgenic mice.

Functional indices for sciatic, peroneal, and posterior tibial nerve lesions in the mouse.

The sciatic functional index previously described in rats has proven to be a reliable index of functional recovery following sciatic nerve injury and repair. A similar functional assay of sciatic, peroneal, and posterior tibial nerve lesions was developed in a mouse model. Forty-eight C57/BL6 mice were randomly divided into 4 groups: sham surgery, sciatic nerve transection, peroneal nerve transection, and posterior tibial nerve transection. Preoperative and postoperative (48 hours) walking tracks were obtained. The pawprints were analyzed in a blinded fashion for measurements of print length (PL), toe spread (TS), intermediate toe spread (IT), and the orthogonal distance from the toe of one paw to the hind pad of the opposite paw (TOF). Multiple linear regression analysis was performed using these measurements to determine their significance and appropriate weighted contribution to the index formula for each nerve lesion. For the sciatic functional index, changes in the PL (P = 0.0092) and TS (P = 0.0008) were significant, resulting in an R2 value of 0.88. For the peroneal functional index, only TS (P < 0.0001) was significant with R2 = 0.83. For the posterior tibial index, only PL (P < 0.0001) was significant with R2 = 0.89. Formulas for a sciatic, peroneal, and posterior tibial functional index were created based on the coefficients derived from the multiple linear regression analysis. The indices that were developed will allow investigators to assess functional recovery following specific nerve lesions in mice.