Oxidative damage and reduction of redox factor-1 expression after transient spinal cord ischemia in rabbits

Masahiro Sakurai, Tetsuya Nagata, Koji Abe, Takashi Horinouchi, Yasuto Itoyama, Koichi Tabayashi

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Objective: The mechanism of spinal cord injury has been thought to be related to the vulnerability of spinal motor neuron cells against ischemia. However, the mechanisms of such vulnerability are not fully understood. We previously reported that spinal motor neurons may be lost by programmed cell death and thus now investigate a possible mechanism of neuronal death with immunohistochemical analysis for 8-hydroxy-2′-deoxyguanosine (8-OHdG) and redox factor-1 (Ref-1). Methods: We used a rabbit spinal cord ischemia model with a balloon catheter. The spinal cord was removed at 8 hours, 1, 2, or 7 days after 15 minutes of transient ischemia, and histologic changes were studied with hematoxylin-eosin staining. Western blot analysis for Ref-1, temporal profiles of 8-OHdG and Ref-1 immunoreactivity, and double-label fluorescence immunocytochemical studies were performed. Results: Most motor neurons were preserved until 2 days but were selectively lost at 7 days of reperfusion. Western blot analysis of a sample from sham control spinal cord showed a characteristic 37-kDa band that was reduced after ischemia. Immunohistochemistry showed the nuclear expression of Ref-1 in motor neurons of control spinal cords, and immunoreactivity was decreased 1 day after ischemia. On the other hand, no nuclear expression was seen of 8-OHdG in motor neurons of control spinal cords, and immunoreactivity was increased 1 day after ischemia. Double-label fluorescence immunocytochemical study revealed that both 8-OHdG and Ref-1 were positive at 8 hours of reperfusion in the same motor neurons, which eventually die. Conclusion: These results suggest that Ref-1 decreased in motor neurons after transient spinal cord ischemia and that this reduction preceded oxidative DNA damage. The reduction of Ref-1 protein at the moderately late stage of reperfusion may be one of the factors responsible for the delay in neuronal death after spinal cord ischemia.

Original languageEnglish
Pages (from-to)446-452
Number of pages7
JournalJournal of Vascular Surgery
Volume37
Issue number2
DOIs
Publication statusPublished - Feb 1 2003

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Spinal Cord Ischemia
Motor Neurons
Oxidation-Reduction
Rabbits
Ischemia
Spinal Cord
Reperfusion
Fluorescence
Western Blotting
Hematoxylin
Eosine Yellowish-(YS)
Spinal Cord Injuries
DNA Damage
Statistical Factor Analysis
Cell Death
Catheters
Immunohistochemistry
Staining and Labeling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

Oxidative damage and reduction of redox factor-1 expression after transient spinal cord ischemia in rabbits. / Sakurai, Masahiro; Nagata, Tetsuya; Abe, Koji; Horinouchi, Takashi; Itoyama, Yasuto; Tabayashi, Koichi.

In: Journal of Vascular Surgery, Vol. 37, No. 2, 01.02.2003, p. 446-452.

Research output: Contribution to journalArticle

Sakurai, Masahiro ; Nagata, Tetsuya ; Abe, Koji ; Horinouchi, Takashi ; Itoyama, Yasuto ; Tabayashi, Koichi. / Oxidative damage and reduction of redox factor-1 expression after transient spinal cord ischemia in rabbits. In: Journal of Vascular Surgery. 2003 ; Vol. 37, No. 2. pp. 446-452.
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