Neuroprotective effects of activated protein C through induction of insulin-like growth factor-1 (IGF-1), IGF-1 receptor, and its downstream signal phosphorylated serine-threonine kinase after spinal cord ischemia in rabbits

Stroke. 2006 Apr;37(4):1081-6. doi: 10.1161/01.STR.0000206280.30972.21. Epub 2006 Feb 16.

Abstract

Background and purpose: Activated protein C (APC) has beneficial effects on ischemia reperfusion injury in neuron. However, the possible mechanism of such beneficial effects is not fully understood. The aim of this study was to investigate the effects and possible mechanisms of APC on ischemic spinal cord damage.

Methods: After induction of spinal cord ischemia, APC (group A) or vehicle (group I) was injected intravenously. Severity of ischemic damage was analyzed by counting the number of motor neurons. To investigate the mechanisms by which APC prevents ischemic spinal cord damage, we performed immunoreactivity and Western blotting of insulin-like growth factor 1 (IGF-1), IGF-1 receptor, and phosphorylated serine-threonine kinase (p-Akt).

Results: APC eased the functional deficits and increased the number of motor neurons after ischemia. Immunoreactivity of IGF-1 in group A was stronger than in group I at 8 hours after reperfusion but was at the same level at 1 day. Induction of IGF-1 receptor and the downstream factor p-Akt was stronger and more prolonged in group A.

Conclusions: These results indicate that induction of IGF-1, IGF-1 receptor, and p-Akt might partially explain the neuroprotective effects of APC after transient spinal cord ischemia in rabbit.

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Count
  • Humans
  • Immunohistochemistry
  • Injections, Intravenous
  • Insulin-Like Growth Factor I / biosynthesis*
  • Ischemia / metabolism
  • Ischemia / pathology
  • Ischemia / physiopathology*
  • Motor Neurons / drug effects
  • Motor Neurons / pathology
  • Nervous System / physiopathology
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / pharmacology*
  • Phosphorylation
  • Protein C
  • Proto-Oncogene Proteins c-akt / biosynthesis*
  • Rabbits
  • Receptor, IGF Type 1 / biosynthesis*
  • Signal Transduction
  • Spinal Cord / blood supply*
  • Spinal Cord / pathology
  • Time Factors

Substances

  • Neuroprotective Agents
  • Protein C
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1
  • Proto-Oncogene Proteins c-akt