Activation of nuclear factor-κB in the brain after experimental subarachnoid hemorrhage and its potential role in delayed brain injury

PLoS One. 2013;8(3):e60290. doi: 10.1371/journal.pone.0060290. Epub 2013 Mar 25.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Brain / drug effects
  • Brain / metabolism*
  • Brain Injuries / etiology*
  • Brain Injuries / pathology
  • Disease Models, Animal
  • Enzyme Activation / drug effects
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interleukin-1beta / metabolism
  • Male
  • NF-kappa B / metabolism*
  • Proline / analogs & derivatives
  • Proline / pharmacology
  • Protein Transport
  • Rabbits
  • Subarachnoid Hemorrhage / complications*
  • Subarachnoid Hemorrhage / metabolism*
  • Thiocarbamates / pharmacology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antioxidants
  • Interleukin-1beta
  • NF-kappa B
  • Thiocarbamates
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1
  • prolinedithiocarbamate
  • Proline

Grants and funding

The National Natural Science Foundation of China (NSFC): No. 81000503(MZ), No. 81070921, and No. 81271297 (JS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.