title: Potential contribution of nuclear factor-kappaB to cerebral vasospasm after experimental subarachnoid hemorrhage in rabbits.
abstract: Nuclear factor-kappaB (NF-kappaB) plays a key role in inflammation, which is involved in the development of cerebral vasospasm after subarachnoid hemorrhage (SAH). In the present study, we assessed the potential role of NF-kappaB in regulation of cerebral vasospasm. Nuclear factor-kappaB DNA-binding activity was measured in cultured vascular smooth muscle cells (VSMCs) treated with hemolysate and pyrrolidine dithiocarbamate (PDTC, 80 micromol/L), an inhibitor of NF-kappaB. Forty-two rabbits were divided into three groups: control, SAH, and PDTC groups (n=14 for each group). The caliber of the basilar artery was evaluated. Nuclear factor-kappaB DNA-binding activity and the gene expression levels of cytokines and adhesion molecules in the basilar artery were measured. Immunohistochemical study was performed to assess the expression and localization of tumor necrosis factor (TNF)-alpha, intercellular adhesion molecule (ICAM)-1, and myeloperoxidase (MPO). It was observed that NF-kappaB DNA-binding activity was significantly increased by treatment with hemolysate in cultured VSCMs, but this increase was suppressed by pretreatment with PDTC. Severe vasospasm was observed in the SAH group, which was attenuated in the PDTC group. Subarachnoid hemorrhage could induce increases of NF-kappaB DNA-binding activity and the gene expression levels of TNF-alpha, interleukin (IL)-1 beta, ICAM-1, and vascular cell adhesion molecule (VCAM)-1, which were reduced in the PDTC group. Immunohistochemical study demonstrated that the expression levels of TNF-alpha, ICAM-1, and MPO were all increased in the SAH group, but these increases were attenuated in the PDTC group. Our results suggest that NF-kappaB is activated in the arterial wall after SAH, which potentially leads to vasospasm development through induction of inflammatory response.
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Meng-Liang
authors.initials: ML
authors.lastname: Zhou
authors.forename: Ji-Xin
authors.initials: JX
authors.lastname: Shi
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Hang
authors.forename: Hui-Lin
authors.initials: HL
authors.lastname: Cheng
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Qi
authors.forename: Lei
authors.initials: L
authors.lastname: Mao
authors.forename: Ke-Fei
authors.initials: KF
authors.lastname: Chen
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Yin
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001488:Basilar Artery / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D024202:Electrophoretic Mobility Shift Assay; D015870:Gene Expression / Q000187:drug effects; D007150:Immunohistochemistry; D007249:Inflammation / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism*; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D013859:Thiocarbamates / Q000494:pharmacology; D020301:Vasospasm, Intracranial / Q000209:etiology / Q000378:metabolism* / Q000473:pathology
chemical_list: D000975:Antioxidants; D015815:Cell Adhesion Molecules; D016207:Cytokines; D016328:NF-kappa B; D013859:Thiocarbamates; C066229:prolinedithiocarbamate; D011392:Proline