The regenerative deficit of peripheral nerves in experimental diabetes: its extent, timing and possible mechanisms

Diabetes mellitus is reported to impair peripheral nerve regeneration, but the extent, timing and selectivity of the deficit is unclear. We studied re generation of motor and sensory fibres in mice with experimental diabetes i nduced using streptozotocin (STZ). The mouse model featured several advanta ges over its counterpart in rats given STZ, while exhibiting the expected s lowing of motor conduction velocity. Serial studies addressed fibre regrowt h for up to 10 weeks after both sciatic nerve crush injury and complete sci atic nerve transection. Following nerve crush, there was a delay in motor f ibre reinnervation of tibial innervated interosseous muscles of diabetics, manifest as a slow recovery of the M-wave recorded from these muscles. Desp ite an apparent recovery in M-waves by 6 weeks, this was not accounted for by restitution of tibial axon numbers in diabetic mice. Histological studie s distal to crush or transection identified substantial delays in the regro wth of the numbers and calibre of regenerating myelinated fibres in diabeti cs for up to 8-10 weeks. Moreover, this delay was observed in both the tibi al (largely motor) and sural (non-motor) distal sciatic branches. There was an associated delay in macrophage invasion and their later resorption in t he diabetic nerves, indicating that a potential mechanism of impaired regen eration might be abnormal macrophage participation in nerve repair. Our fin dings indicate that during nerve regeneration, diabetic motor and sensory f ibres have substantial and persistent deficits in regrowth associated with abnormalities in macrophage participation.