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Immune System Augmentation by Glatiramer Acetate of Peripheral Nerve Regeneration – Crush vs. Transection Models of Rat Sciatic Nerve
Shai Luria, MD; Avi Cohen; Ori Safran; Shimon Firman; Meir Liebergall
Hadassah-Hebrew University Medical Center, Jerusalem, Israel
Immune system augmentation, using the antigen glatiramer acetate (GA, Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel) which is known to affect T-cell immunity, has been shown to have a positive effect on peripheral nerve regeneration. The aim of this study was to evaluate a larger dose of GA (1000 microgm), and to compare the effect of GA on the regeneration of crushed versus transected nerves.
Wild type rats underwent crush or transection and repair injuries to the sciatic nerve and were treated with either GA, complete Freund’s Adjuvant (CFA) or saline. They were examined 3 weeks post injury both histologically (axon count) and functionally (tibialis anterior muscle weight and sciatic function index - footprint analysis).
GA was found to augment the regeneration of the peripheral nerve both histologically and functionally. In the transected nerve a significant increase (p<0.04) in the axon count distal to the injury site was seen in the GA group in comparison with the CFA control group. A similar yet insignificant trend was found in the crushed nerve. A significant improvement (p<0.04) was found in the footprint analysis between the GA and the saline control group in both the crush and transected nerve groups. We found no difference in the axon count or in the muscle weight between the injury types, although we did find a significant improvement in the footprint analysis in the crush group in comparison with the transected groups (p<0.0001).
The higher dose of GA tested in this study was found to significantly improve the regeneration of the peripheral nerve. In both injury types, the functional results improved with GA, although histologically it significantly improved the transected nerve axon count, in comparison with the crushed nerve. While comparing the two injury types, we saw a discrepancy between the different functional measures examined. The nerve may have sufficiently regenerated after both injury types at 3 weeks, to result in a similar proximal (tibialis anterior) muscle weight. On the other hand, the transected nerve was not as efficient as the crushed nerve in reinnervating the more distal and complex muscle functions, which resulted in a significant difference in the footprint analysis.
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