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 regeneration of motor and sensory fibres in mice with experimental diabetes induced using streptozotocin (STZ). The mouse model featured several advantages over its counterpart in rats given STZ, while exhibiting the expected slowing of motor conduction velocity. Serial studies addressed fibre regrowth for up to 10 weeks after both sciatic nerve crush injury and complete sciatic nerve transection. Following nerve crush, there was a delay in motor fibre reinnervation of tibial innervated interosseous muscles of diabetics, manifest as a slow recovery of the M-wave recorded from these muscles. Despite an apparent recovery in M-waves by 6 weeks, this was not accounted for by restitution of tibial axon numbers in diabetic mice. Histological studies distal to crush or transection identified substantial delays in the regrowth of the numbers and calibre of regenerating myelinated fibres in diabetics for up to 8-10 weeks. Moreover, this delay was observed in both the tibial (largely motor) and sural (non-motor) distal sciatic branches. There was an associated delay in macrophage invasion and their later resorption in the diabetic nerves, indicating that a potential mechanism of impaired regeneration might be abnormal macrophage participation in nerve repair. Our findings indicate that during nerve regeneration, diabetic motor and sensory fibres have substantial and persistent deficits in regrowth associated with abnormalities in macrophage participation.
Kennedy
J M
JM
Department of Clinical Neurosciences and the Neuroscience Research Group, University of Calgary, Calgary, Alberta, Canada.
Zochodne
D W
DW
D000818:Animals; D001284:Atrophy; D001369:Axons / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004576:Electromyography; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D009046:Motor Neurons / Q000502:physiology; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000502:physiology*; D009431:Neural Conduction / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology; D012584:Sciatic Nerve / Q000473:pathology / Q000502:physiology; D013497:Sural Nerve / Q000473:pathology / Q000502:physiology