Survival and death-promoting events after transient spinal cord ischemia in rabbits: Induction of Akt and caspase3 in motor neurons

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

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Objective: The mechanism of spinal cord injury has been thought to be related to the vulnerability of spinal motor neuron cells to ischemia. However, the mechanisms of such vulnerability are not fully understood. We previously reported that spinal motor neurons might be lost as a result of programmed cell death and investigated a possible mechanism of neuronal death by means of immunohistochemical analysis for CPP32 (caspase3) and serine-threonine kinase (Akt). Methods: We used a rabbit spinal cord ischemia model with use of a balloon catheter. The spinal cord was removed at 8 hours or 1, 2, or 7 days after 15 minutes of transient ischemia, and histologic changes were studied with hematoxylin and eosin staining. Western blot analysis for Akt and caspase3, temporal profiles of Akt and caspase3 immunoreactivity, and double-label fluorescence immunocytochemical studies were performed. Results: The majority of motor neurons were preserved until 2 days but were selectively lost at 7 days of reperfusion. Western blot analysis revealed no immunoreactivity for Akt and caspase3 in the sham-operated spinal cords. However, such immunoreactivity became apparent at 8 hours after transient ischemia, decreased at 1 day, and returned to the baseline level at 2 days. A double-label fluorescence immunocytochemical study revealed that both Akt and caspase3 were positive at 8 hours of reperfusion in the same motor neurons, which eventually die. Conclusion: These results suggests that transient spinal cord ischemia activates both cell death and survival pathways after ischemia. The activation of Akt protein at the early stage of reperfusion might be one of the factors responsible for the delay in neuronal death after spinal cord ischemia.

Original languageEnglish
Pages (from-to)370-377
Number of pages8
JournalJournal of Thoracic and Cardiovascular Surgery
Volume125
Issue number2
DOIs
Publication statusPublished - Feb 1 2003

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

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