PloS one, 2013-03, Vol.8 (3), p.e60290-e60290
2013
Details
- Autor(en) / Beteiligte
- Titel
- Activation of nuclear factor-κB in the brain after experimental subarachnoid hemorrhage and its potential role in delayed brain injury
- Ist Teil von
- PloS one, 2013-03, Vol.8 (3), p.e60290-e60290
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2013
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0060290Titel-ID: cdi_plos_journals_1330893693
- Format
- –
- Schlagworte
- Activation, Adhesion tests, Animals, Antioxidants - pharmacology, Apoptosis, Binding, Biology, Brain, Brain - drug effects, Brain - metabolism, Brain Injuries - etiology, Brain Injuries - pathology, Brain injury, Cell adhesion, Cell adhesion & migration, Cell death, Cytokines, Deoxyribonucleic acid, Disease Models, Animal, DNA, Electrophoretic mobility, Enzyme Activation - drug effects, Genes, Head injuries, Hemorrhage, IL-1β, Immunohistochemistry, Inflammation, Intercellular adhesion molecule 1, Intercellular Adhesion Molecule-1 - metabolism, Interleukin-1beta - metabolism, Interleukins, Ischemia, Laboratory animals, Leukemia, Male, Medicine, Neurons, Neurosurgery, NF-kappa B - metabolism, NF-κB protein, Polymerase chain reaction, Proline - analogs & derivatives, Proline - pharmacology, Protein Transport, Pyrrolidine, Pyrrolidine dithiocarbamate, Rabbits, Stroke, Subarachnoid hemorrhage, Subarachnoid Hemorrhage - complications, Subarachnoid Hemorrhage - metabolism, Thiocarbamates - pharmacology, Transcription, Transcription factors, Traumatic brain injury, Tumor Necrosis Factor-alpha - metabolism, Tumor necrosis factor-TNF, Tumor necrosis factor-α