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Role of protein kinase C in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage. 1993

M Sako, and J Nishihara, and S Ohta, and J Wang, and S Sakaki
Department of Neurosurgery, Ehime University School of Medicine, Japan.

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.

UI MeSH Term Description Entries
D007537 Isometric Contraction Muscular contractions characterized by increase in tension without change in length. Contraction, Isometric,Contractions, Isometric,Isometric Contractions
D011493 Protein Kinase C An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. Calcium Phospholipid-Dependent Protein Kinase,Calcium-Activated Phospholipid-Dependent Kinase,PKC Serine-Threonine Kinase,Phospholipid-Sensitive Calcium-Dependent Protein Kinase,Protein Kinase M,Calcium Activated Phospholipid Dependent Kinase,Calcium Phospholipid Dependent Protein Kinase,PKC Serine Threonine Kinase,Phospholipid Sensitive Calcium Dependent Protein Kinase,Phospholipid-Dependent Kinase, Calcium-Activated,Serine-Threonine Kinase, PKC
D002546 Ischemic Attack, Transient Brief reversible episodes of focal, nonconvulsive ischemic dysfunction of the brain having a duration of less than 24 hours, and usually less than one hour, caused by transient thrombotic or embolic blood vessel occlusion or stenosis. Events may be classified by arterial distribution, temporal pattern, or etiology (e.g., embolic vs. thrombotic). (From Adams et al., Principles of Neurology, 6th ed, pp814-6) Brain Stem Ischemia, Transient,Cerebral Ischemia, Transient,Crescendo Transient Ischemic Attacks,Transient Ischemic Attack,Anterior Circulation Transient Ischemic Attack,Brain Stem Transient Ischemic Attack,Brain TIA,Brainstem Ischemia, Transient,Brainstem Transient Ischemic Attack,Carotid Circulation Transient Ischemic Attack,Posterior Circulation Transient Ischemic Attack,TIA (Transient Ischemic Attack),Transient Ischemic Attack, Anterior Circulation,Transient Ischemic Attack, Brain Stem,Transient Ischemic Attack, Brainstem,Transient Ischemic Attack, Carotid Circulation,Transient Ischemic Attack, Posterior Circulation,Transient Ischemic Attack, Vertebrobasilar Circulation,Transient Ischemic Attacks, Crescendo,Vertebrobasilar Circulation Transient Ischemic Attack,Attack, Transient Ischemic,Attacks, Transient Ischemic,Brainstem Ischemias, Transient,Cerebral Ischemias, Transient,Ischemia, Transient Brainstem,Ischemia, Transient Cerebral,Ischemias, Transient Brainstem,Ischemias, Transient Cerebral,Ischemic Attacks, Transient,TIA, Brain,TIAs (Transient Ischemic Attack),Transient Brainstem Ischemia,Transient Cerebral Ischemia,Transient Cerebral Ischemias,Transient Ischemic Attacks
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001488 Basilar Artery The artery formed by the union of the right and left vertebral arteries; it runs from the lower to the upper border of the pons, where it bifurcates into the two posterior cerebral arteries. Arteries, Basilar,Artery, Basilar,Basilar Arteries
D013345 Subarachnoid Hemorrhage Bleeding into the intracranial or spinal SUBARACHNOID SPACE, most resulting from INTRACRANIAL ANEURYSM rupture. It can occur after traumatic injuries (SUBARACHNOID HEMORRHAGE, TRAUMATIC). Clinical features include HEADACHE; NAUSEA; VOMITING, nuchal rigidity, variable neurological deficits and reduced mental status. Hemorrhage, Subarachnoid,Perinatal Subarachnoid Hemorrhage,Subarachnoid Hemorrhage, Aneurysmal,Subarachnoid Hemorrhage, Spontaneous,SAH (Subarachnoid Hemorrhage),Subarachnoid Hemorrhage, Intracranial,Aneurysmal Subarachnoid Hemorrhage,Aneurysmal Subarachnoid Hemorrhages,Hemorrhage, Aneurysmal Subarachnoid,Hemorrhage, Intracranial Subarachnoid,Hemorrhage, Perinatal Subarachnoid,Hemorrhage, Spontaneous Subarachnoid,Hemorrhages, Aneurysmal Subarachnoid,Hemorrhages, Intracranial Subarachnoid,Hemorrhages, Perinatal Subarachnoid,Hemorrhages, Spontaneous Subarachnoid,Hemorrhages, Subarachnoid,Intracranial Subarachnoid Hemorrhage,Intracranial Subarachnoid Hemorrhages,Perinatal Subarachnoid Hemorrhages,SAHs (Subarachnoid Hemorrhage),Spontaneous Subarachnoid Hemorrhage,Spontaneous Subarachnoid Hemorrhages,Subarachnoid Hemorrhage, Perinatal,Subarachnoid Hemorrhages,Subarachnoid Hemorrhages, Aneurysmal,Subarachnoid Hemorrhages, Intracranial,Subarachnoid Hemorrhages, Perinatal,Subarachnoid Hemorrhages, Spontaneous
D013755 Tetradecanoylphorbol Acetate A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA. Phorbol Myristate Acetate,12-Myristoyl-13-acetylphorbol,12-O-Tetradecanoyl Phorbol 13-Acetate,Tetradecanoylphorbol Acetate, 4a alpha-Isomer,12 Myristoyl 13 acetylphorbol,12 O Tetradecanoyl Phorbol 13 Acetate,13-Acetate, 12-O-Tetradecanoyl Phorbol,Acetate, Phorbol Myristate,Acetate, Tetradecanoylphorbol,Myristate Acetate, Phorbol,Phorbol 13-Acetate, 12-O-Tetradecanoyl,Tetradecanoylphorbol Acetate, 4a alpha Isomer

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