Schwann cell is a target in ischemia-reperfusion injury to peripheral nerve

Haruyasu Iida, Ann M. Schmeichel, Yanping Wang, James D. Schmelzer, Phillip A. Low

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)761-766
Number of pages6
JournalMuscle and Nerve
Issue number6
StatePublished - Dec 2004


  • Apoptosis
  • Ischemia
  • Peripheral nerve
  • Reperfusion
  • Schwann cell

ASJC Scopus subject areas

  • Physiology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Physiology (medical)


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