Floor plan - 2013 Annual Meeting - American Association for Hand ...

Antibodies to Galactocerebroside Enhance Nerve Regeneration after Acute Contusion and Transection Injuries
in the Adult Rat Sciatic Nerve
Institution where the work was prepared: University of California, Irvine, Orange, CA, USA
Aaron M. Kosins, MD, MBA; Charles Mendoza; Michael P. McConnell, MD; Brandon Shepard; Sanjay Dhar, PhD;
Gregory RD Evans, MD, FACS; Hans S. Keirstead, PhD; University of California, Irvine
INTRODUCTION:
To improve the regenerative potential of PNS axons in vivo, we utilize a novel therapy in the adult rat sciatic nerve in which nerve regeneration
is enhanced following contusion and transection injuries. We demonstrate that 1) Axon regeneration within a region of injury
increases in the presence of immunological demyelination, and 2) Regenerated axons are derived from the proximal motor axons.
METHODS:
Adult female Sprague-Dawley sciatic nerves were contused and injected with the demyelinating agent. The sciatic nerves were harvested
14 and 28 days following the onset of demyelination. The lesion containing length of nerve was cut into 1mm transverse blocks and
processed to preserve the cranio-caudal orientation. In a second group, the sciatic nerves were exposed, transected, repaired, and
injected with the demyelinating agent. These animals were similarly euthanized at 1 and 2 months and processed to examine the extent
of axon regeneration. Specimens were fixed and evaluated using structural and immunohistochemical analysis. A Mini-Ruby Tracer was
included to determine the source and direction of axonal re-growth.
RESULTS:
A single epineural injection of complement proteins plus antibodies to galactocerebroside (the major myelin sphingolipid) resulted in
demyelination followed by Schwann cell remyelination that enhanced nerve regeneration in the injured (contusion and transection) animals.
At each time point for both contused and transected animals, nerve regeneration was enhanced following demyelination therapy.
Tracers demonstrated that nerve regeneration arose from proximal motor axons, and not the distal branching of sensory axons.
CONCLUSION:
These studies demonstrate a new method to enhance nerve regeneration in the PNS using experimental immunological demyelination.
Our findings indicate that peripheral nerve regeneration within a region of contusion or transection injury in the adult rat sciatic
nerve can be enhanced using a demyelinating agent. This data can be applied in the creation of tissue-engineered constructs, cellbased
therapy systems, and even nerve transfers to improve the outcome of critical nerve injuries in the PNS.
Sympathetic Nerves in the Tarsal Tunnel: Implications for Blood Flow in the Diabetic Foot
Institution where the work was prepared: University of Arizona School of Medicine, Tucson, AZ, USA
Andrew Blount, BS; Erika Dexter; Raymond Nagle; Christopher Maloney; Lee Dellon; Ziv Peled; University of Arizona
BACKGROUND:
Peripheral nerve decompression has been shown to alter the natural history of lower extremity peripheral neuropathy by reducing the
incidence of ulceration and amputation. One method by which this occurs is an increase in protective sensation in the decompressed
foot. Another possible method, which has yet to be evaluated, is an improvement in blood flow resulting from sympathectomy of the
tibial vasculature which takes place during tarsal tunnel decompression surgery.
METHODS:
Seven consecutive patients evaluated at our clinic were enrolled in this pilot study which was approved by the Institutional Review Board
of our university. All patients had neuropathy as documented by their clinical history, physical exam, and by neurosensory testing using
the Pressure Specified Sensory Device (PSSD) (Sensory Management Services L.L.C., Baltimore, MD). During tarsal tunnel decompression,
all patients had a partial epineurectomy of the tibial nerve, a portion of which was sent as a specimen. Connective tissue bridging
the tibial nerve and vessels was also harvested and sent for evaluation. Specimens were analyzed by immunohistochemistry using an
anti-tyrosine hydroxylase antibody, which is specific for sympathetic nerves.
RESULTS:
Five of seven tibial epineurial specimens stained positively with TH. Six of seven connective tissue specimens stained positively with TH.
In those specimens that were negative, no nerve tissue of any type was identified. Staining was especially apparent surrounding the
microvasculature in each specimen (Fig 1).
CONCLUSION:
Sympathetic nerves are present adjacent to the tibial vessels and microvasculature within the tarsal tunnel. Sympathectomy occurring
during tarsal tunnel decompression may account for increased blood flow to the foot, a concept supported by our identification of sympathetic
nerve fibers along the local microvasculature in our specimens. This mechanism has several implications. One, it may help
explain how tarsal tunnel decompression functions in preventing future ulceration and amputation. Furthermore, if blood flow is
improved after decompression and epineurectomy, perhaps our tarsal tunnel release procedure could be considered an adjunct to
bypass surgery in patients with lower extremity peripheral vascular disease. In the future, we plan to perform more direct blood flow
measurements and correlate these data with similar immunohistochemical findings.
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