Role of protein kinase C in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage.
This study investigated the role of protein kinase C (PKC) in the pathogenesis of vasospasm after experimental subarachnoid hemorrhage (SAH). PKC activation by intracisternal injection of a phorbol ester [12-O-tetradecanoylphorbol-13-acetate (TP)] induced dose-dependent, slowly developing, severe contraction of the basilar artery. A single intracisternal injection of TP (5 x 10(-9) M in the CSF) induced sustained contraction lasting over 3 days, which almost paralleled the changes of membrane-bound PKC activity in the basilar arterial wall. In a two-hemorrhage SAH model, membrane-bound PKC activity in the basilar artery increased up to day 4 and returned to the control level by day 14, whereas angiographic contraction reached a maximum on day 7 and still persisted at a moderate level on day 14. Thus, there was a discrepancy between arterial PKC activity and arterial contraction. Multiple intracisternal injections of TP produced 30-40% sustained contraction of the basilar artery lasting for more than 10 days along with sustained activation of PKC to levels compatible with that observed in the SAH model. However, TP injection caused considerably milder histological changes in the basilar artery than those noted in the SAH model. We concluded that cerebral vasospasm after SAH cannot be explained solely on the basis of activation of the PKC pathway.
Sako
M
M
Department of Neurosurgery, Ehime University School of Medicine, Japan.
Nishihara
J
J
Ohta
S
S
Wang
J
J
Sakaki
S
S
D000818:Animals; D001488:Basilar Artery / Q000201:enzymology / Q000503:physiopathology / Q000648:ultrastructure; D004285:Dogs; D002546:Ischemic Attack, Transient / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D007537:Isometric Contraction; D011493:Protein Kinase C / Q000502:physiology*; D013345:Subarachnoid Hemorrhage / Q000503:physiopathology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate