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Activation of Nuclear Factor-κB in the Brain after Experimental Subarachnoid Hemorrhage and Its Potential Role in Delayed Brain Injury

It has been reported that inflammation is involved in brain injury after subarachnoid hemorrhage (SAH). Nuclear factor-κB (NF-κB) is a key transcriptional regulator of inflammatory genes. Here, we used pyrrolidine dithiocarbamate(PDTC), an inhibitor of NF-κB, through intracisternal injection to stud...

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Autores principales: You, Wan-Chun, Wang, Chun-xi, Pan, Yun-xi, Zhang, Xin, Zhou, Xiao-ming, Zhang, Xiang-sheng, Shi, Ji-xin, Zhou, Meng-liang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3607578/
https://www.ncbi.nlm.nih.gov/pubmed/23536907
http://dx.doi.org/10.1371/journal.pone.0060290
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author You, Wan-Chun
Wang, Chun-xi
Pan, Yun-xi
Zhang, Xin
Zhou, Xiao-ming
Zhang, Xiang-sheng
Shi, Ji-xin
Zhou, Meng-liang
author_facet You, Wan-Chun
Wang, Chun-xi
Pan, Yun-xi
Zhang, Xin
Zhou, Xiao-ming
Zhang, Xiang-sheng
Shi, Ji-xin
Zhou, Meng-liang
author_sort You, Wan-Chun
collection PubMed
description It has been reported that inflammation is involved in brain injury after subarachnoid hemorrhage (SAH). Nuclear factor-κB (NF-κB) is a key transcriptional regulator of inflammatory genes. Here, we used pyrrolidine dithiocarbamate(PDTC), an inhibitor of NF-κB, through intracisternal injection to study the role of NF-κB in delayed brain injury after SAH. A total of 55 rabbits were randomly divided into five groups: the control group; the SAH groups including Day-3, 5, and 7 SAH groups (the rabbits in these groups were sacrificed at 3, 5, 7 days after SAH, respectively); and the PDTC group (n = 11 for each group). Electrophoretic mobility shift assay (EMSA) was performed to detect NF-κB DNA-binding activity. The mRNA levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and intercellular adhesion molecule (ICAM)-1 were evaluated by RT-PCR analysis. Deoxyribonucleic acid fragmentation was detected by TUNEL and p65 immunoactivity was assessed by immunohistochemistry. Our results showed the activation of NF-κB after SAH, especially at day 3 and 5. The activated p65 was detected in neurons. NF-κB DNA-binding activity was suppressed by intracisternal administration of PDTC. Increased levels of the TNF-α, IL-1β, and ICAM-1 mRNA were found in the brain at day 5 after SAH, and which were suppressed in the PDTC group. The number of TUNEL-positive cells also decreased significantly in the PDTC group compared with that in the Day-5 SAH group. These results demonstrated that the activated NF-κB in neurons after SAH plays an important role in regulating the expressions of inflammatory genes in the brain, and ultimately contributes to delayed brain injury.
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spelling pubmed-36075782013-03-27 Activation of Nuclear Factor-κB in the Brain after Experimental Subarachnoid Hemorrhage and Its Potential Role in Delayed Brain Injury You, Wan-Chun Wang, Chun-xi Pan, Yun-xi Zhang, Xin Zhou, Xiao-ming Zhang, Xiang-sheng Shi, Ji-xin Zhou, Meng-liang PLoS One Research Article It has been reported that inflammation is involved in brain injury after subarachnoid hemorrhage (SAH). Nuclear factor-κB (NF-κB) is a key transcriptional regulator of inflammatory genes. Here, we used pyrrolidine dithiocarbamate(PDTC), an inhibitor of NF-κB, through intracisternal injection to study the role of NF-κB in delayed brain injury after SAH. A total of 55 rabbits were randomly divided into five groups: the control group; the SAH groups including Day-3, 5, and 7 SAH groups (the rabbits in these groups were sacrificed at 3, 5, 7 days after SAH, respectively); and the PDTC group (n = 11 for each group). Electrophoretic mobility shift assay (EMSA) was performed to detect NF-κB DNA-binding activity. The mRNA levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and intercellular adhesion molecule (ICAM)-1 were evaluated by RT-PCR analysis. Deoxyribonucleic acid fragmentation was detected by TUNEL and p65 immunoactivity was assessed by immunohistochemistry. Our results showed the activation of NF-κB after SAH, especially at day 3 and 5. The activated p65 was detected in neurons. NF-κB DNA-binding activity was suppressed by intracisternal administration of PDTC. Increased levels of the TNF-α, IL-1β, and ICAM-1 mRNA were found in the brain at day 5 after SAH, and which were suppressed in the PDTC group. The number of TUNEL-positive cells also decreased significantly in the PDTC group compared with that in the Day-5 SAH group. These results demonstrated that the activated NF-κB in neurons after SAH plays an important role in regulating the expressions of inflammatory genes in the brain, and ultimately contributes to delayed brain injury. Public Library of Science 2013-03-25 /pmc/articles/PMC3607578/ /pubmed/23536907 http://dx.doi.org/10.1371/journal.pone.0060290 Text en © 2013 You et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
You, Wan-Chun
Wang, Chun-xi
Pan, Yun-xi
Zhang, Xin
Zhou, Xiao-ming
Zhang, Xiang-sheng
Shi, Ji-xin
Zhou, Meng-liang
Activation of Nuclear Factor-κB in the Brain after Experimental Subarachnoid Hemorrhage and Its Potential Role in Delayed Brain Injury
title Activation of Nuclear Factor-κB in the Brain after Experimental Subarachnoid Hemorrhage and Its Potential Role in Delayed Brain Injury
title_full Activation of Nuclear Factor-κB in the Brain after Experimental Subarachnoid Hemorrhage and Its Potential Role in Delayed Brain Injury
title_fullStr Activation of Nuclear Factor-κB in the Brain after Experimental Subarachnoid Hemorrhage and Its Potential Role in Delayed Brain Injury
title_full_unstemmed Activation of Nuclear Factor-κB in the Brain after Experimental Subarachnoid Hemorrhage and Its Potential Role in Delayed Brain Injury
title_short Activation of Nuclear Factor-κB in the Brain after Experimental Subarachnoid Hemorrhage and Its Potential Role in Delayed Brain Injury
title_sort activation of nuclear factor-κb in the brain after experimental subarachnoid hemorrhage and its potential role in delayed brain injury
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3607578/
https://www.ncbi.nlm.nih.gov/pubmed/23536907
http://dx.doi.org/10.1371/journal.pone.0060290
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