title: Delayed paraplegia after spinal cord ischemic injury requires caspase-3 activation in mice.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Charlestown, MA 02129, USA.
authors.forename: Manabu
authors.initials: M
authors.lastname: Kakinohana
authors.forename: Kotaro
authors.initials: K
authors.lastname: Kida
authors.forename: Shizuka
authors.initials: S
authors.lastname: Minamishima
authors.forename: Dmitriy N
authors.initials: DN
authors.lastname: Atochin
authors.forename: Paul L
authors.initials: PL
authors.lastname: Huang
authors.forename: Masao
authors.initials: M
authors.lastname: Kaneki
authors.forename: Fumito
authors.initials: F
authors.lastname: Ichinose
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D010264:Paraplegia / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D020760:Spinal Cord Ischemia / Q000150:complications / Q000378:metabolism* / Q000473:pathology
chemical_list: D053148:Caspase 3