Ischemia-reperfusion injury of peripheral nerve in experimental diabetic neuropathy.
The pathogenesis of human diabetic neuropathy likely involves the interplay of hyperglycemia, ischemia, and oxidative stress. Mild-moderate ischemia-reperfusion to streptozotocin (STZ)-induced diabetes results in florid fiber degeneration in diabetic but not in normal nerves. Uncertainty exists as to the influence of duration of diabetes on this susceptibility. We therefore studied diabetic tibial and sciatic nerves using a rat ischemia-reperfusion (IR) model after 1 month and 4 months of diabetes utilizing electrophysiological, behavioral, and neuropathological methods. Electrophysiological abnormalities were present in 1-month diabetic rats (D) and persisted over 4 months. Behavioral scores were decreased markedly at 4 months (p<0.05). Endoneurial edema and ischemia fiber degeneration (IFD) were observed at both the 1-month (p<0.01 and p<0.001) and 4-month (p<0.001) durations in diabetic nerves, whereas only mild or no damage was observed in age-matched control nerves. These findings demonstrate that STZ-induced diabetes exacerbates the morphological and electrophysiological pathology in peripheral nerve to IR injury both in the early timepoint of 1 month and late timepoint of 4 months, although there was a gradation of injury, which is more severe at the later timepoint. Reperfusion exaggerated morphological pathology in 1-month STZ-induced diabetic peripheral nerve.
Wang
Yanping
Y
Department of Neurology, Mayo Clinic, 811 Guggenheim, 200 First Street SW, Rochester, MN 55905, USA.
Schmelzer
James D
JD
Schmeichel
Ann
A
Iida
Haruyasu
H
Low
Phillip A
PA
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications*; D004195:Disease Models, Animal; D004487:Edema / Q000209:etiology; D007839:Functional Laterality; D007511:Ischemia / Q000150:complications*; D008297:Male; D009410:Nerve Degeneration / Q000209:etiology; D009431:Neural Conduction / Q000502:physiology; D010525:Peripheral Nerves / Q000473:pathology* / Q000528:radiation effects; D010523:Peripheral Nervous System Diseases / Q000209:etiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications*; D012584:Sciatic Nerve / Q000473:pathology / Q000503:physiopathology; D013979:Tibial Nerve / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors