Potential Contribution of Nuclear Factor-κB to Cerebral Vasospasm after Experimental Subarachnoid Hemorrhage in Rabbits

Abstract

Nuclear factor-κB (NF-κB) 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-κB in regulation of cerebral vasospasm. Nuclear factor-κB DNA-binding activity was measured in cultured vascular smooth muscle cells (VSMCs) treated with hemolysate and pyrrolidine dithiocarbamate (PDTC, 80 μmol/L), an inhibitor of NF-κB. 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-κB 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)-α, intercellular adhesion molecule (ICAM)-1, and myeloperoxidase (MPO). It was observed that NF-κB 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-κB DNA-binding activity and the gene expression levels of TNF-α, interleukin (IL)-1β, 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-α, 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-κB is activated in the arterial wall after SAH, which potentially leads to vasospasm development through induction of inflammatory response.