Schwann cell is a target in ischemia-reperfusion injury to peripheral nerve.
Ischemia-reperfusion (IR) causes oxidative injury and ischemic fiber degeneration due to injury of the neuron and axon. In this study, we explore the effect of oxidative stress on Schwann cells, as a specific peripheral nerve target, using our established rat model for IR injury. Fifty-six rats were used. Six groups (N = 8 each) underwent complete hindlimb ischemia for 4 h, followed by reperfusion durations of 0 h, 3 h, 7 days, 14 days, 28 days, and 42 days. One group underwent sham operation (N = 8). We evaluated immunohistochemical labeling for oxidative injury using anti-8-hydroxydeoxyguanosine (8-OHdG). To identify cells committed to apoptosis, we studied immunolabeling to caspase-3 and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) positivity. Only minimal positivity was seen in the sham, 0-h, and 3-h groups. Positivity to 8-OHdG, caspase-3, and TUNEL increased significantly in groups undergoing longer reperfusion (8-OHdG, 7-28 days; caspase-3, 14-42 days; TUNEL, 14-42 days). The positive cells surrounding axons were identified as being Schwann cells by their configuration and colabeling with S-100. We conclude that apoptosis of Schwann cells occurs during reperfusion and continues even when axons regenerate. Schwann cell apoptosis could contribute to impairment of axonal function and efficiency of fiber regeneration. Both these abnormalities are known to occur in experimental and human diabetic nerves.
Mayo Clinic College of Medicine, Department of Neurology, 811 Guggenheim Building, 200 First Street SW, Rochester, Minnesota 55905, USA.
Haruyasu
H
Iida
Ann M
AM
Schmeichel
Yanping
Y
Wang
James D
JD
Schmelzer
Phillip A
PA
Low
D000818:Animals; D008297:Male; D018384:Oxidative Stress / Q000502:physiology; D010525:Peripheral Nerves / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology*; D012583:Schwann Cells / Q000378:metabolism / Q000473:pathology*