Delayed paraplegia after spinal cord ischemic injury requires caspase-3 activation in mice

Manabu Kakinohana, Kotaro Kida, Shizuka Minamishima, Dmitriy N. Atochin, Paul L. Huang, Masao Kaneki, Fumito Ichinose

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background and Purpose-Delayed paraplegia remains a devastating complication after ischemic spinal cord injury associated with aortic surgery and trauma. Although apoptosis has been implicated in the pathogenesis of delayed neurodegeneration, mechanisms responsible for the delayed paraplegia remain incompletely understood. The aim of this study was to elucidate the role of apoptosis in delayed motor neuron degeneration after spinal cord ischemia. Methods-Mice were subjected to spinal cord ischemia induced by occlusion of the aortic arch and left subclavian artery for 5 or 9 minutes. Motor function in the hind limb was evaluated up to 72 hours after spinal cord ischemia. Histological studies were performed to detect caspase-3 activation, glial activation, and motor neuron survival in the serial spinal cord sections. To investigate the impact of caspase-3 activation on spinal cord ischemia, outcome of the spinal cord ischemia was examined in mice deficient for caspase-3. Results-In wild-type mice, 9 minutes of spinal cord ischemia caused immediate paraplegia, whereas 5 minutes of ischemia caused delayed paraplegia. Delayed paraplegia after 5 minutes of spinal cord ischemia was associated with histological evidence of caspase-3 activation, reactive astrogliosis, microglial activation, and motor neuron loss starting at approximately 24 to 48 hours after spinal cord ischemia. Caspase-3 deficiency prevented delayed paraplegia and motor neuron loss after 5 minutes of spinal cord ischemia, but not immediate paraplegia after 9 minutes of ischemia. Conclusions-The present results suggest that caspase-3 activation is required for delayed paraplegia and motor neuron degeneration after spinal cord ischemia.

Original languageEnglish
Pages (from-to)2302-2307
Number of pages6
JournalStroke
Volume42
Issue number8
DOIs
Publication statusPublished - Aug 2011
Externally publishedYes

Keywords

  • apoptosis
  • cleaved caspase-3
  • delayed neuronal death
  • delayed paraplegia
  • spinal cord ischemia

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'Delayed paraplegia after spinal cord ischemic injury requires caspase-3 activation in mice'. Together they form a unique fingerprint.

  • Cite this

    Kakinohana, M., Kida, K., Minamishima, S., Atochin, D. N., Huang, P. L., Kaneki, M., & Ichinose, F. (2011). Delayed paraplegia after spinal cord ischemic injury requires caspase-3 activation in mice. Stroke, 42(8), 2302-2307. https://doi.org/10.1161/STROKEAHA.110.600429