title: Inhibition of c-Jun N-terminal kinase pathway attenuates cerebral vasospasm after experimental subarachnoid hemorrhage through the suppression of apoptosis.
abstract: 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.
authors.affiliation: Department of Physiology, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA.
authors.forename: H
authors.initials: H
authors.lastname: Yatsushige
authors.forename: M
authors.initials: M
authors.lastname: Yamaguchi-Okada
authors.forename: C
authors.initials: C
authors.lastname: Zhou
authors.forename: J W
authors.initials: JW
authors.lastname: Calvert
authors.forename: J
authors.initials: J
authors.lastname: Cahill
authors.forename: A R T
authors.initials: AR
authors.lastname: Colohan
authors.forename: J H
authors.initials: JH
authors.lastname: Zhang
mesh_terms: 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*
chemical_list: D000873:Anthracenes; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases