Mouse Rapid-Stretch Nerve Injury Model
Mark A. Mahan, MD1; Stewart Yeoh, PhD2; Wesley Warner, BS2; (1)Department of Neurosurgery, University of Utah, Salt Lake City, UT, (2)University of Utah, Salt Lake City, UT
Mouse rapid-stretch nerve injury model
Mark A. Mahan, MD1, Wesley Warner, BS1, Stewart Yeoh, PhD2
Objective: While the majority of adult brachial plexus injuries result from high speed mechanisms, no laboratory model has been created to model rapid-stretch nerve injuries. We sought to assess the regenerative capacity of nerves subjected to rapid-stretch injuries.
Methods: The sciatic nerves of 48 Thy-1-YFP transgenic mice were dissected and subjected to rapid-stretch injury methods. Rapid-stretch injury involved fixed direction strain produced via constrained weight drop applied to an intact nerve. Four injury severity levels were produced with rapid-stretch: sham, elastic (stretch with return to pre-existing length), plastic (persistent length change) and rupture. Animals underwent behavioral testing with Von Frey fibers, tapered-beam, paw-print analysis serially for 48 days and then were euthanized. Nerve histology, wet muscle weight, and muscle histology was performed.
Results: Decline in functional performance testing mirrored injury severity. In both sciatic function index and tapered beam testing, sham animals demonstrated no change in performance; animals with an elastic-stretched nerve demonstrated modest functional deficits and returned to baseline by 15 days; animals with a plastic-stretched nerve demonstrated worse function and returned to near baseline at 48 days; animals with a ruptured nerve demonstrated the most severe functional deficits, but also improved in tapered-beam performance. Wet muscle weight demonstrated profound decreases in both ipsilateral and contralateral triceps surae and tibialis anterior in both plastic and ruptured conditions. Nerve histology demonstrated infrequent neuroma-in-continuity in only plastic-stretched nerves; ruptured nerves all produced stump neuromas – despite proximity to the distal stump. Elastic-stretched nerves demonstrated mild evidence of reorganization. Osmium staining demonstrated severe reduction in fiber counts that reflected nerve injury severity.
Conclusions: Rapid-stretch injuries to nerve in a rodent model appear to reproduce similar patterns of regeneration as human injuries, particularly similar to the pattern of recovery seen in birth brachial plexus palsy. Animals demonstrate significant adaptation on functional performance, despite severe levels of nerve injury. Neuroma-in-continuity could be clearly defined, but variably produced in a mouse model.
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