title: Intracisternal administration of SB203580, a p38 mitogen-activated protein kinase inhibitor, attenuates cerebral vasospasm via inhibition of tumor-necrosis factor-α.
abstract: Tumor-necrosis factor-α (TNF-α) is critical to the development of cerebral vasospasm after subarachnoid hemorrhage (SAH). Hence, therapeutic strategies targeting TNF-α can attenuate cerebral vasospasm. This study investigated the effects of SB203580, a p38 mitogen-activated protein kinase (MAPK) inhibitor, on TNF-α concentration in the cerebral arteries and the cerebrospinal fluid (CSF) after SAH and on subsequent cerebral vasospasm. Twenty-three rabbits were divided into four groups: (i) control (without SAH), (ii) SAH (SAH only), (iii) dimethylsulfoxide (DMSO, vehicle), and (iv) SB203580. The severity of vasospasm and the immunoreactivities of TNF-α and phosphorylated p38 MAPK in the brain vessels were determined in all animals, and the concentrations of TNF-α in the CSF were also assessed. Severe vasospasm was observed in the rabbits from the SAH and DMSO groups. SB203580 reversed vasospasm after SAH. Lower immunoreactivities of TNF-α and phosphorylated p38 MAPK were found in the basilar artery in the SB203580 group than in the DMSO group. The concentration of TNF-α in the CSF increased after SAH, but treatment with SB203080 after SAH suppressed this increase. Our data show that SB203580 reversed cerebral vasospasm by inhibiting the phosphorylation of p38 MAPK in the basilar artery and by suppressing the increase in TNF-α in the basilar artery and CSF after SAH. SB203580 could therefore potentially be used for the treatment of cerebral vasospasm after SAH.
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, Jiangsu, China.
authors.forename: Yun-Xi
authors.initials: YX
authors.lastname: Pan
authors.forename: Ke-Fei
authors.initials: KF
authors.lastname: Chen
authors.forename: Yi-Xing
authors.initials: YX
authors.lastname: Lin
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Zhou
authors.forename: Xiang-Sheng
authors.initials: XS
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Ji-Xin
authors.initials: JX
authors.lastname: Shi
mesh_terms: D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000473:pathology; D004121:Dimethyl Sulfoxide / Q000627:therapeutic use; D004195:Disease Models, Animal; D007093:Imidazoles / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D011817:Rabbits; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000188:drug therapy* / Q000209:etiology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000097:blood / Q000134:cerebrospinal fluid; D020301:Vasospasm, Intracranial / Q000188:drug therapy* / Q000209:etiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000187:drug effects
chemical_list: D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; D004121:Dimethyl Sulfoxide