Ischemia-reperfusion injury causes oxidative stress and apoptosis of Schwann cell in acute and chronic experimental diabetic neuropathy

Antioxid Redox Signal. Nov-Dec 2005;7(11-12):1513-20. doi: 10.1089/ars.2005.7.1513.


Mild ischemia-reperfusion (IR) injury to diabetic peripheral nerve is known to cause severe ischemic fiber degeneration. Little information is available on its effects on Schwann cell (SC). In this study, we evaluated oxidative stress and apoptosis of SC following mild IR, using immunohistochemistry in streptozotocin (STZ)- induced diabetic rats. Twenty-six rats were divided into four groups according to the duration of diabetes: 1- month STZ-induced diabetic group (n=7) and age-matched control group (n=7); 4-month STZ-induced diabetic group (n=6) and age-matched control group (n=6). Using our established IR model of 3 h of ischemia followed by 7 days of reperfusion, sciatic and tibial nerves were harvested and labeled with 8-hydroxydeoxyguanosine (8-OHdG; oxidative stress marker), caspase-3 (apoptotic executor), and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) activity (apoptotic indicator). Marked positive staining with 8-OHdG, caspase-3, and TUNEL were found in diabetic ischemic nerves (right side) following IR in both 1-month and 4-month groups. Only mild positive staining or no staining was seen in the nonischemic side (left side) of diabetic and age-matched control groups. Co-labeling with S-100 confirmed that the cells labeled with 8-OHdG, caspase3, and TUNEL were SC. SC was susceptible to oxidative injury and apoptosis in experimental diabetic neuropathy when subjected to mild IR injury.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Acute Disease
  • Aging / physiology
  • Animals
  • Apoptosis*
  • Caspase 3
  • Caspases / metabolism
  • Chronic Disease
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / pharmacology
  • Diabetes Mellitus, Experimental
  • Diabetic Neuropathies / complications
  • Diabetic Neuropathies / metabolism*
  • Diabetic Neuropathies / pathology*
  • Immunohistochemistry
  • Male
  • Oxidative Stress*
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / complications
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology*
  • Schwann Cells / metabolism*
  • Schwann Cells / pathology*


  • 8-Hydroxy-2'-Deoxyguanosine
  • Casp3 protein, rat
  • Caspase 3
  • Caspases
  • Deoxyguanosine