Plastic Surgery Research Council
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PSRC 60th Annual Meeting

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Single Treatment With Alpha-1-antitrypsin Enhances Nerve Regeneration After Peripheral Nerve Injury
Christine Radtke, Prof. Dr., Sabina Janciauskiene, Prof. Dr., Kerstin Reimers, Prof. Dr., Peter M. Vogt, Prof. Dr..
Hannover Medical Schoool, Hannover, Germany.

PURPOSE
Macrophages play a key role in axonal regeneration because they secrete IL-6 that is necessary for axonal guidance and remyelination. Pro-inflammatory cytokines stimulate macrophage migration into the lesion sites which is necessary for the removal of cell debris and Schwann cell invasion as guidance for axonal outgrowth followed by remyelination. α1-antitrypsin (AAT) is an acute phase protein and it is shown to express anti-inflammatory characteristics in neutrophil and monocyte/macrophage driven models in vitro and in vivo. We asked a question whether AAT can affect regeneration of injured peripheral nerve fibers by initial macrophage mobilization. We have established several models to study peripheral nerve injuries in small animals. In the rat sciatic nerve crush model we developed a standardized method for investigation of nerve regeneration parameters. We could demonstrate that axonal sprouting, as well as myelin sheaths and functional outcome can be improved by adjunct AAT therapy.
METHODS
In vivo sciatic nerves of adult rats were exposed and crushed for 20 sec with fine forceps to transect all axons. Immediately after nerve crush, AAT was injected proximally and distally to the lesion site in a standardized sciatic nerve crush site through a glass pipette attached to a Hamiliton syringe. During the course of the experiments the animals were tested behaviorally for functional improvement. After 21 days, the nerves were removed and histology was performed.
RESULTS
In vitro, we have demonstrated that AAT inhibits endotoxin-stimulated TNFa, IL-6, IL-1β and enhances IL-10 expression in human monocytes, neutrophils, and endothelial cells. The application of AAT into an acute axotomy model led to the significantly improved axonal regeneration and re-myelination than compared control animals. Moreover, not only histological, but also functional improvement was observed following direct injection of AAT after acute peripheral nerve lesion. Our results indicate that AAT delivered into injured peripheral nerve participate in neural repair.
CONCLUSIONS
AAT is an acute phase protein which improves peripheral nerve regeneration. Further studies are needed to delineate cellular mechanisms involved in these new biological activities of AAT.


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