A morphological and functional study of peripheral nerve and skeletal muscle regeneration in experimental diabetes
This study investigates the effects of two treatments; α-lipoic acid (100mgkg-1) and an α-lipoic acid (18mgkg-1)/γ-linolenic acid (23mgkg-1) conjugate, on peripheral nerve regeneration, in diabetic rats, following a punctate freeze lesion injury. Streptozotocin-induced diabetes caused a significant delay in sciatic nerve regeneration, in terms of myelinated fibre distribution and area. By 3 weeks post injury a 54% deficit in fibre distribution was evident in untreated diabetics. A significant decrement in fibre area was also observed. The level of regeneration attained by non-diabetic controls 3 weeks after injury was not achieved in diabetic animals until approximately 6 weeks. The remyelination of regenerating fibres was significantly impaired in untreated diabetics compared to non-diabetic controls. These diabetic induced deficits in regenerative capacity were prevented by treatment with LA and the LA/GLA conjugate. These treatments combine antioxidant activity and a vasodilatory effect to promote endoneurial blood flow. A significant reduction in nerve blood flow occurs in diabetes and amelioration of this effect is thought to enhance nerve regeneration. Treatment with the individual components, LA (18mgkg-1) and GLA (23mgkg-1) was without effect in preventing the delayed regeneration of diabetic nerve. It therefore appears that, when administered in combination, these substances exhibit a marked synergy. Overall the results presented in this thesis indicate that treatment with either high doses of α-lipoic acid or an α-lipoic acid/γ-linolenic acid conjugate may be effective in preventing degenerative deficits associated with diabetic neuropathy.