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A Novel Model to Measure the Regenerative Potential of the Peripheral Nervous System after Experimental Immunological Demyelination

Kosins, Aaron M. M.D., M.B.A.; McConnell, Michael P. M.D.; Mendoza, Charles B.S.; Shepard, Brandon; Scholz, Thomas M.D.; Evans, Gregory R. D. M.D.; Keirstead, Hans S. Ph.D.

Plastic and Reconstructive Surgery: June 2009 - Volume 123 - Issue 6 - p 1688-1696
doi: 10.1097/PRS.0b013e3181a65a27
Experimental: Original Articles

Background: Immunological demyelination is a proposed strategy to improve nerve regeneration in the peripheral nervous system. To investigate the remyelinating potential of Schwann cells in vivo in the peripheral nervous system, the authors have reproduced and expanded upon a novel model of immunological demyelination in the adult rat sciatic nerve. The authors demonstrate (1) the peripheral nervous system’s quantitative, regenerative response to immunological demyelination and (2) whether Schwann cells within a region of demyelination are induced to divide in the presence of demyelinated axons.

Methods: The sciatic nerves of female Sprague-Dawley rats were exposed and injected with demyelinating agent bilaterally. At 3 days (n = 3), 7 days (n = 3), and 14 days (n = 3), the animals were euthanized for histological evaluation. A second group of animals (n = 3) was similarly injected with demyelinating agent and then exposed to bromodeoxyuridine between 48 and 72 hours after the onset of demyelination. These animals were euthanized soon after the last injection of bromodeoxyuridine. The tissue was analyzed for Schwann cells (labeled with antibodies to S100) and bromodeoxyuridine assay.

Results: A single epineural injection of complement proteins plus antibodies to galactocerebroside resulted in demyelination followed by Schwann cell remyelination. At 3 days after injection, peripheral nerve demyelination and Schwann cell proliferation were evident. Maximum demyelination was seen at 7 days; however, Schwann cell proliferation and remyelination peaked at 14 days after injection.

Conclusions: These studies demonstrate an immunological model of demyelination and remyelination in the peripheral nervous system and quantitatively measure regenerative potential. This model will be used to isolate nerve segments and to measure their regenerative potential when given demyelinating agent after acute contusion and transection injuries.

Irvine and Orange, Calif.

From the Reeve-Irvine Research Center and the Department of Tissue Engineering and Regenerative Medicine, Aesthetic and Plastic Surgery Institute, University of California, Irvine.

Received for publication June 10, 2008; accepted December 23, 2008.

Presented at the Plastic Surgery Research Council meeting, in Dana Point, California, in 2006 and the American Society for Peripheral Nerve meeting, in San Juan, Puerto Rico, in 2007.

Disclosure: The authors have no financial interest or commercial associations in any products, devices, or drugs used in this study.

Aaron M. Kosins, M.D., M.B.A., University of California, Irvine, Aesthetic and Plastic Surgery Institute, 200 South Manchester Avenue, Suite 650, Orange, Calif. 92868,

©2009American Society of Plastic Surgeons