Artikel
Intrasurgical electrical stimulation of proximal nerve stumps prior to implantation of biohybride nerve transplants shows capacities to improve peripheral nerve regeneration across long gaps
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Veröffentlicht: | 20. Mai 2009 |
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Objective: We investigated if intrasurgical electrical stimulation of proximal nerve stumps (ES) speeds up peripheral nerve regeneration (PNR) across long gaps. Furthermore, we were interested if functional motor recovery (FMR) would be facilitated by the treatment.
Methods: Sciatic nerves of adult rats were transsected proximally to their trifurcation. Animals were divided into a non-stimulated control group (A) and an electrically stimulated group (B). ES (1h, 20Hz) was applied using a special electrode. Silicone tubes were used to bridge a 13mm gap between the separated nerve stumps. Transplantation of Schwann cells (SC) is known to facilitate PNR across long gaps. Therefore, silicone tubes were differentially filled for acellular (A-1, B-1) and cellular (A-2, B-2) transplantation conditions. In A-1/B-1, tubes were filled with growth factor-reduced Matrigel (GFR-Matrigel). In A-2/B-2, highly enriched neonatal rat SC were suspended in GFR-Matrigel.
Results: Four weeks after surgery, group A-1 showed regenerated nerve tissue bridging the 13 mm gap in 11% (n=1/9) of the animals. In group B-1, 22% (n=2/9) of the animals showed gap bridging tissue regeneration. In contrast, treatment in group A-2 resulted in 87.5% (n=7/8) gap bridging regenerates, while group B-2 demonstrated 100% (n=8/8) tissue regeneration. Eight weeks after surgery, group A-1 showed 33% (n=3/9) tissue regeneration compared to only 22% (n=2/9) in group B-1. However, group A-2 demonstrated gap-bridging tissue in 69% (n=11/16) of the animals and group B-2 in 79% (n=15/19). Furthermore, exclusively SC transplantation plus ES resulted in FMR: evocable hind paw movements and positive electromyography (in 13% (n=2/15) of macroscopically regenerated nerves).
Conclusions: ES demonstrates potential to increase PNR across long gaps. This capacity is dependent on the presence of transplanted SC. Morphometrical analyses of regenerated myelinated axons as well as quantification of retrogradely labelled regenerating neurons are currently performed to further estimate the quality of PNR. Follow-up studies will be initiated to elucidate the potential to improve FMR by intrasurgical short-term electrical stimulation. Financial support: Stiftung Neurochirurgische Forschung, HiLF-program Hanover Medical School. * R. Schmitte, D. Klode contributed equally.