Apoptosis of motor neurons with induction of caspases in the spinal cord after ischemia

T. Hayashi, M. Sakurai, Koji Abe, M. Sadahiro, K. Tabayashi, Y. Itoyama

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Abstract

Background and Purpose - Some neuronal subpopulations are especially vulnerable to ischemic injury. In the spinal cord, large motor neurons are vulnerable to ischemia and are selectively lost after transient ischemia. However, the mechanisms of the neuronal loss have been uncertain. We hypothesized that spinal motor neurons might be lost by apoptosis and investigated a possible mechanism of neuronal death by detection of double- strand breaks in genomic DNA and immunohistochemical analysis for caspases, ie, interleukin-1β converting enzyme (ICE), Nedd-2, and CPP32. Methods - We used a rabbit spinal cord ischemia model created with a balloon catheter. The spinal cord was removed at 8 hours, 1, 2, or 7 days after 15 minutes of transient ischemia, and histological changes were studied with hematoxylin- eosin staining. To detect double-strand breaks in DNA, a staining with terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL) was performed. Furthermore, expression of ICE, Nedd-2, and CPP32 was investigated by Western blotting and immunohistochemical analysis. Results - Motor neurons were selectively lost at 7 days after transient ischemia. TUNEL study demonstrated that no cells were positively labeled until 1 day after ischemia, but nuclei of some motor neurons were positively labeled at 2 days. Western blot analysis revealed no immunoreactivity for ICE and slight immunoreactivities for Nedd-2 and CPP32 in the sham-operated spinal cords. However, immunoreactivity became apparent at 8 hours after transient ischemia, decreased at 1 day, and returned to baseline level at 2 days. Immunohistochemical analysis demonstrated that motor neurons were responsible for induction of those caspases. Conclusions - Double-strand breaks in genomic DNA and induction of three caspases were demonstrated. These results indicate that motor neuron death in the spinal cord after transient ischemia is profoundly associated with activation of apoptotic processes.

Original languageEnglish
Pages (from-to)1007-1013
Number of pages7
JournalStroke
Volume29
Issue number5
Publication statusPublished - May 1998

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Keywords

  • Apoptosis
  • Ischemia
  • Motor neuron
  • Rabbit
  • Spinal cord

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

Cite this

Hayashi, T., Sakurai, M., Abe, K., Sadahiro, M., Tabayashi, K., & Itoyama, Y. (1998). Apoptosis of motor neurons with induction of caspases in the spinal cord after ischemia. Stroke, 29(5), 1007-1013.