Glatiramer Acetate Immune System Augmentation for Peripheral Nerve Regeneration in Rat Crushed Sciatic Nerve Model

Shai Luria; Thanapong Waitayawinyu; Conniff, James; Morton, H. Josette; Nemechek, Nicholas M.; Sonnen, Joshua A.; Katolik, Leonid I.; Trumble, Thomas E.
February 2010
Journal of Bone & Joint Surgery, American Volume;Feb2010, Vol. 92-A Issue 2, p396
Academic Journal
Background: Protective antiself response to nervous system injury has been reported to be mediated by a T-cell subpopulation that can recognize self-antigens. Immune cells have been shown to play a role in the regulation of motor neuron survival after a peripheral nerve injury. The objective of the present study was to evaluate the effects of immune system augmentation with use of the antigen glatiramer acetate, which is known to affect T-cell immunity, on peripheral nerve regeneration. Methods: Wild-type and nude-type (T-cell-deficient) rats underwent crush injury of the sciatic nerve. Three and six weeks after the injury, the sciatic nerve was examined, both functionally (on the basis of footprint analysis and the tibialis anterior muscle response and weight) and histologically (on the basis of axon count). Results: Significantly greater muscle responses were measured after three weeks in the group of wild-type rats that were treated with glatiramer acetate (control limb:injured limb ratio, 0.05 for the glatiramer acetate group [n = 9], compared with 0.51 for the saline solution group [n = 8]; p < 0.05). Higher axon counts were also found in this group (control limb:injured limb ratio, -0.07 for the glatiramer acetate group [n = 10], compared with 0.29 for the saline solution group [n = 8]; p < 0.05). The nude-type rats showed no response to the intervention after three weeks but showed a delayed response after six weeks. A second dose of glatiramer acetate, delivered forty-eight hours after the injury, did not result in an improved response as compared with the control groups. Conclusions: We found that a single treatment with glatiramer acetate resulted in accelerated functional and histological recovery after sciatic nerve crush injury. The role of T-cell immunity in the mechanism of glatiramer acetate was suggested by the partial and late response found in the T-cell-deficient rats. Clinical Relevance: Peripheral nerve injury may result in severe loss of sensation, weakness, and pain. The recovery is usually not complete with the limited treatment options. The recruitment of an endogenous mechanism, the immune system, to better coordinate the regeneration of nerves after injury is a different approach to this difficult clinical problem.


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