%0 Journal Article
%T Biphasic Activation of Nuclear Factor-Kappa B in Experimental Models of Subarachnoid Hemorrhage In Vivo and In Vitro
%A Wan-Chun You
%A Wei Li
%A Zong Zhuang
%A Yong Tang
%A Hu-Chen Lu
%A Xiang-Jun Ji
%A Wei Shen
%A Ji-Xin Shi
%A Meng-Liang Zhou
%J Mediators of Inflammation
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/786242
%X It has been proven that nuclear factor-kappa B (NF-百B) is activated as a well-known transcription factor after subarachnoid hemorrhage (SAH). However, the panoramic view of NF-百B activity after SAH remained obscure. Cultured neurons were signed into control group and six hemoglobin- (Hb-) incubated groups. One-hemorrhage rabbit SAH model was produced, and the rabbits were divided randomly into one control group and five SAH groups. NF-百B activity was detected by electrophoretic mobility shift assay (EMSA) and immunohistochemistry. Real-time polymerase chain reaction (PCR) was performed to assess the downstream genes of NF-百B. NeuN immunofluorescence and lactate dehydrogenase (LDH) quantification were used to estimate the neuron injury. Double drastically elevated NF-百B activity peaks were detected in rabbit brains and cultured neurons. The downstream gene expressions showed an accordant phase peaks. NeuN-positive cells decreased significantly in day 3 and day 10 groups. LDH leakage exhibited a significant increase in Hb-incubated groups, but no significant difference was found between the Hb incubated groups. These results suggested that biphasic increasing of NF-百B activity was induced after SAH, and the early NF-百B activity peak indicated the injury role on neurons; however, the late peak might not be involved in the deteriorated effect on neurons. 1. Introduction Aneurysmal subarachnoid hemorrhage (SAH) accounts for 5% of all stroke cases [1], and patients with aneurysmal SAH are at high risk of developing permanent neurological deficits [2]. Based on the failure of clinic treatment focusing on the vasospasm, the researches shifted to brain injury, especially early brain injury (EBI) which is considered the most common cause of disability and mortality after SAH [3, 4]. It has been demonstrated that a number of pathways were implicated in the development of EBI including apoptotic and inflammatory pathways, which have a mutual impact on neurons. Nuclear factor-kappa B (NF-百B) is composed of 5 subunits: p65, p50, p52, RelB, and c-Rel, which can form heterodimer or homodimer. The most common heterodimer in central nervous system is p50/p65 [5每8]. NF-百B is a transcription factor regulating numerous genes, such as inflammatory cytokines, apoptotic mediators, growth factors, adhesion molecules, and enzymes, which all are involved in pivotal cellular pathophysiology processes [9每12]. NF-百B is maintained in the cytoplasm in a nonactivated form by combining with an inhibitor subunit, IkappaB (I百B). In response to activating stimuli, I百B is phosphorylated by
%U http://www.hindawi.com/journals/mi/2012/786242/