title: Inhibition of the p38 mitogen-activated protein kinase (MAPK) pathway attenuates cerebral vasospasm following experimental subarachnoid hemorrhage in rabbits.
abstract: The p38 mitogen-activated protein kinase (MAPK) plays an important role in apoptosis and is also involved in the development of cerebral vasospasm after subarachnoid hemorrhage (SAH). Here, we sought to examine whether inhibition of p38 MAPK could attenuate cerebral vasospasm and investigate the underlying mechanisms in a rabbit SAH model. SAH was established in rabbits (n=12/group) using the double-hemorrhage method. We observed apparent vasospasm in the basilar arteries of rabbits with SAH, which was significantly attenuated by SB203580, a selective p38MAPK inhibitor. Immunoblotting assays showed enhanced phosphorylation of p38 MAPK and ATF2 and increased caspase-3 cleavage following SAH, which were, however, markedly suppressed by SB203580. TUNEL staining further revealed significant apoptosis in the basilar arteries of rabbits with SAH, which was scantly present in rabbits treated with SB203580. Our results demonstrated that p38 MAPK was activated in cerebral vasospasm and associated with increased apoptosis in the basilar arteries and p38 MAPK inhibition suppressed apoptosis, suggesting that p38 MAPK could be a novel therapeutic target for cerebral vasospasm.
authors.affiliation: Department of Neurosurgery, Jinling Hospital; 305 East Zhongshan Road, Nanjing 210002, P.R. China.
authors.forename: Xing
authors.initials: X
authors.lastname: Zhang
authors.forename: Xu Dong
authors.initials: XD
authors.lastname: Zhao
authors.forename: Ji Xin
authors.initials: JX
authors.lastname: Shi
authors.forename: Hong Xia
authors.initials: HX
authors.lastname: Yin
mesh_terms: D051698:Activating Transcription Factor 2 / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001488:Basilar Artery / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D007276:Injections, Intraventricular; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology*; D011817:Rabbits; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology; D020301:Vasospasm, Intracranial / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D051698:Activating Transcription Factor 2; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580