Impaired nerve fiber regeneration in axotomized peripheral nerves in streptozotocin‐diabetic rats

Abstract

Aim/Introduction: Impaired nerve fiber regeneration is a salient feature of diabetic neuropathy. Its pathogenesis is still unclear. We attempted to characterize the structure of regenerated myelinated fibers after transection in streptozotocin-diabetic rats. Materials and Methods: Streptozotocin-diabetic rats underwent transection of the sciatic nerve. Two and 4 weeks postaxotomy, regenerated myelinated fibers of the cut end and fibers at its proximal site were morphometrically examined. Non-diabetic control rats with axotomy were also examined for comparison. Results: At 4 weeks post-axotomy, diabetic rats showed an increased myelinated fiber density and total fiber number with a trend toward reduced fiber size at the cut end compared with those in control rats. The average number of myelin lamellae relative to axonal size in regenerated fibers at the cut end was significantly reduced in diabetic rats compared with that in control rats. The proximal site showed a reduced size of fibers and axons in both diabetic and control rats to a similar extent compared with those in a non-axotomized state. At 2 weeks post-axotomy, these findings were less apparent. Conclusions: The nerves of diabetic rats when axotomized undergo impaired regeneration characterized by increased fiber density with hypomyelination. (J Diabetes Invest,

Impaired Axonal Regeneration in Diabetes. Perspective on the Underlying Mechanism from In Vivo and In Vitro Experimental Studies

“…Considering that the explant culture lacks the process of Wallerian degeneration and subsequent regenerative events at the site distal to injury, it seems more likely that the excess of regenerating fibers in diabetes may impede appropriate target reinnervation and functional recovery. This hypothesis was supported by the findings of in vivo studies ( 5 , 8 , 69 ), which will be discussed in the next section. Gumy et al ( 36 ) applied the explant culture system to normal adult mice and observed that exposure to high-glucose (60 mM) culture conditions resulted in retardation of neurite outgrowth and Schwann cell migration from DRG explants.…”

“…Delayed Wallerian degeneration, alterations in the structure and function of the ECM components, and enhanced AGE–RAGE signaling axis caused by hyperglycemia can be major obstacles to axonal regrowth after injury. In the second part, we illustrated the excessive regenerative capacity of small nerve fibers under diabetic conditions in vivo and in vitro ( 6 – 8 , 69 ). There is room for further investigation if these findings imply dysfunctional neurite outgrowth that disturbs appropriate target reinnervation and functional recovery.…”

“…By light microscopic and ultrastructural morphometric analyses, we recently evaluated nerve fiber regeneration from axotomized sciatic nerves of STZ-diabetic rats and non-diabetic control rats ( 8 ). Four weeks after axotomy, there was a significant increase in myelinated fiber density and total fiber number at the cut end in diabetic rats relative to those in control rats.…”

“…In this paper, we review the findings from recent studies that focus on how diabetes affects the intrinsic and extrinsic factors of peripheral nerve regeneration. In addition, we discuss our own results from in vivo and in vitro studies, which indicate that defective neurite outgrowth after axonal injury occurs under diabetic conditions ( 6 – 8 ).…”

Gender differences in nerve regeneration after sciatic nerve injury and repair in healthy and in type 2 diabetic Goto-Kakizaki rats

“…The published literature in the field of nerve regeneration in diabetes is limited and studies almost exclusively use streptozotocin-induced diabetes in rats in which blood glucose levels are high (see e.g. [ 11 – 14 ]). The ability of axons to regenerate in relation to the state of the Schwann cells may also be an important point in relation to moderate blood glucose levels and in view of the global increase of diabetes, particularly bearing in mind its most common complication, i.e.…”