Analysis of Nerve Stretch Injury Compared to Crush, Transection with Primary Repair, Transection with Secondary Repair Injuries, and Transection with No Repair
Ilyas Eli, MD1; Stewart Yeoh, PhD1; Wesley Warner, BS1; Mark A. Mahan, MD2
1University of Utah, Salt Lake City, UT, 2Department of Neurosurgery, University of Utah, Salt Lake City, UT
Background:
Although rapid-stretch injury is the most common cause of a segmental loss of nerve, existing animal models of nerve injury (crush or surgical transection) do not mimic stretch induced damage. We have developed a rapid-stretch nerve injury model which we sought to compare to traditional models of nerve injuries: crush, primary repair, secondary repair, and no repair.
Methods:
Eight groups of sciatic nerve injuries were compared, using C57BL/6 and B6.Cg-Tg(Thy1-YFP)HJrs/J male mice (n=[38]). Three groups underwent rapid-stretch injury of different biomechanically determined grades: elastic (<15% persistent length deformation), inelastic (permanent length change), and rupture. Four other groups (n=9 for each group) underwent traditional nerve injury: transection with primary repair, secondary repair at 4 weeks, and no repair as well as crush injury. The final group was sham injured (surgical exposure alone). Behavioral tests included sciatic function index (SFI) walking analysis, tapered beam, and Von Frey sensibility, at selected intervals for a duration of 6 weeks post-surgery. Histological analysis consisted of trichrome, osmium tetroxide, and immunostaining. Wet muscle weight of the gastrocnemius and tibialis anterior muscles was obtained.
Results:
SFI results demonstrated comparable poor outcomes between severe stretch injuries (inelastic stretch and stretch rupture) and the three transection injures (p = [0.9]), whereas crush injury and elastic stretch demonstrated good recovery (p<0.05). For tapered beam, crush and elastic injuries recovered to baseline performance, while the severe stretch and transection injuries demonstrated chronic deficits through 6 weeks (p<.05). For sensation, elastic injury yielded short duration dysfunction and all other injuries had a significant decrease in sensitivity followed by progressive recovery to baseline levels. Only rupture injuries demonstrated chronic desensitization (p<.01). Denervation atrophy of the gastrocnemius was not found in crush and elastic injuries, while all other injuries demonstrated statistically significant atrophy upon harvest (p<.01). Histological assessment depicted only minute architectural disruption in crush and elastic injury grades in comparison to sham. Laminin and NF200 immunostains demonstrated aberrant remodeling of endoneurial tubules and limited axonal regeneration within the nerve fibers of primary, secondary, and no repair injuries, parallel to changes in severe stretch injuries.
Conclusion:
Rapid-stretch injury to nerve depicts neurologic deficits consistent with Seddon's model of clinical injuries. The stretch-induced injuries are similar in outcomes to prior nerve injury models, although different in recovery profiles and different histology. The stretch injury mechanism produces a distinct type of injury which may be useful for examining this type of nerve injury pathophysiology.
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