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.
OBJECTIVE
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.
Yamauchi
Takashi
T
Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Sakurai
Masahiro
M
Abe
Koji
K
Takano
Hiroshi
H
Sawa
Yoshiki
Y
D000818:Animals; D015153:Blotting, Western; D002452:Cell Count; D006801:Humans; D007150:Immunohistochemistry; D007275:Injections, Intravenous; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis*; D007511:Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009046:Motor Neurons / Q000187:drug effects / Q000473:pathology; D009420:Nervous System / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D010766:Phosphorylation; D011486:Protein C; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis*; D011817:Rabbits; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis*; D015398:Signal Transduction; D013116:Spinal Cord / Q000098:blood supply* / Q000473:pathology; D013997:Time Factors
D018696:Neuroprotective Agents; D011486:Protein C; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt