Cyclin D1 and Cdk4 protein induction in motor neurons after transient spinal cord ischemia in rabbits

Masahiro Sakurai, Takeshi Hayashi, Koji Abe, Yasuto Itoyama, Koichi Tabayashi

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Background and Purpose - 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 hypothesized that spinal motor neurons might be lost by programmed cell death and investigated a possible mechanism of neuronal death by detection of double-strand breaks in genomic DNA and immunohistochemical analysis for cyclin D1 and cyclin-dependent kinases (Cdk) 4. Methods - We used a rabbit spinal cord ischemia model with a balloon catheter. Spinal cord was removed at 8 hours and 1, 2, and 7 days after 15 minutes of transient ischemia, and histological changes were studied with hematoxylin-eosin staining. In situ terminal deoxynucleotidyl transferase (TdT)-mediated dUTP- biotin nick-end labeling (TUNEL), DNA fragment with gel electrophoresis, Western blot analysis for cyclin D 1 and Cdk4, and temporal profiles of cyclin D1 anti Cdk4 immunoreactivity were investigated. Results - Most motor neurons were preserved until 2 days but were selectively lost at 7 days of reperfusion. Immunocytochemistry showed positive TUNEL selectively at 2 days of reperfusion in spinal motor neuron nuclei Typical ladders of oligonucleosomal DNA fragments were detected at 2 days of reperfusion. Immunoreactivity of cyclic D1 and Cdk4 proteins was induced selectively at 8 hours in motor neuron nuclei, which eventually died. Conclusions - These results indicate that induction of cyclin D1 and Cdk4 may be implicated in programmed cell death change after transient spinal cord ischemia in rabbits.

Original languageEnglish
Pages (from-to)200-207
Number of pages8
JournalStroke
Volume31
Issue number1
DOIs
Publication statusPublished - Jan 2000

Keywords

  • Cyclin-dependent kinases
  • Cyclins
  • Ischemia
  • Motor neurons
  • Spinal cord

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialised Nursing

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