Inhibition of c-Jun N-terminal kinase pathway attenuates cerebral vasospasm after experimental subarachnoid hemorrhage through the suppression of apoptosis.
BACKGROUND
Recent studies have demonstrated that apoptosis in cerebral arteries could play an essential role in cerebral vasospasm after subarachnoid hemorrhage (SAH) and that SP600125, an inhibitor of c-Jun N-terminal kinase (JNK) could suppress apoptosis. The present study examined whether SP600125 could reduce cerebral vasospasm through the suppression of apoptosis.


METHODS
Fifteen dogs were assigned to 3 groups: control, SAH, and SAH + SP600125 (30 micromol/l). SAH was induced by the injection of autologous blood into the cisterna magna on day 0 and day 2. Angiograms were evaluated on day 0 and day 7. The activation of the JNK pathway and caspase-3 were also evaluated using Western blot. To determine the distribution, TUNEL staining and immunohistochemistry for phosphorylated c-jun and cleaved caspase-3 were performed.


RESULTS
Severe vasospasm was observed in the basilar artery of the SAH dogs. SP600125 reduced angiographic and morphological vasospasm and reduced the expression of cleaved caspase-3, thereby suppressing apoptosis.


CONCLUSIONS
These results demonstrate that SP600125 attenuates cerebral vasospasm through the suppression of apoptosis, which may provide a novel therapeutic target for cerebral vasospasm.
Yatsushige
H
H
Department of Physiology, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA.
Yamaguchi-Okada
M
M
Zhou
C
C
Calvert
J W
JW
Cahill
J
J
Colohan
A R T
AR
Zhang
J H
JH
D000818:Animals; D000873:Anthracenes / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001488:Basilar Artery / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004285:Dogs; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D013345:Subarachnoid Hemorrhage / Q000473:pathology*; D020301:Vasospasm, Intracranial / Q000473:pathology / Q000503:physiopathology*
D000873:Anthracenes; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases