Role of MAPK in chronic cerebral vasospasm.
This study was undertaken to investigate the role of p44/42 MAPK in a dog double hemorrhage model of subarachnoid hemorrhage (SAH), and whether MEK inhibitors can alter the degree of SAH-induced vasoconstriction. The diameter of the basilar artery, which was compared with day 0 angiogram, decreased gradually in a time-dependent manner from day 3 (80%), day 5 (68%) through day 7 (53.5%). The level of MAPK (p44/42) immunoprecipitation peaked on day 3 and remained enhanced through day 7 (P < 0.05). MEK inhibitor PD98059 significantly reduced p44/42 MAPK immunoprecipitation and significantly reversed vasospasm and increased residual diameter to 79.0% on day 7. These results demonstrated that p44/42 MAPK kinase is involved in the pathogenesis of cerebral vasospasm. The MEK inhibitor PD98059 might be useful in the treatment of vasospasm.
Aoki
K
K
Department of Neurosurgery, University of Mississippi Medical Center, Jackson 39216-4505, USA.
Zubkov
A Y
AY
Tibbs
R E
RE
Zhang
J H
JH
D000818:Animals; D001794:Blood Pressure; D002908:Chronic Disease; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004285:Dogs; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D011233:Precipitin Tests; D014661:Vasoconstriction; D020301:Vasospasm, Intracranial / Q000209:etiology* / Q000503:physiopathology
D005419:Flavonoids; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D004121:Dimethyl Sulfoxide