Biphasic activation of nuclear factor kappa B and expression of p65 and c-Rel after traumatic brain injury in rats

Inflamm Res. 2014 Feb;63(2):109-15. doi: 10.1007/s00011-013-0677-1. Epub 2013 Oct 22.

Abstract

Background and object: Nuclear factor kappa B (NF-κB) functions as a key regulator in the central nervous system and regulates the inflammatory pathway. There are two peaks of cerebral NF-κB activation after neonatal hypoxia-ischemia and subarachnoid hemorrhage. Our previous studies found that NF-κB activity was up-regulated at an early stage and remained elevated at day 7 after traumatic brain injury (TBI). However, data are lacking regarding an overview of NF-κB activity and expression of NF-κB subunits after TBI. Hence, the current study was designed to detect the time course of NF-κB activation and expression of NF-κB p65 and c-Rel subunits around the contused cortex following TBI.

Methods: Adult Sprague-Dawley rats were randomly divided into sham and TBI groups at different time points. A TBI model was induced, and then the NF-κB DNA-binding activity in the surrounding areas of injured brain was detected by electrophoretic mobility shift assay. Western blotting was used to measure the protein levels of p65 and c-Rel in the nucleus. The concentrations of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were detected by enzyme-linked immunosorbent assay. Moreover, the distribution of c-Rel and p65 was examined by immunohistochemical studies.

Results: There were double peaks of cerebral cortical NF-κB activity, at 3 and 10 days post-injury. Additionally, protein levels of p65 were found to be elevated and peaked at 3 days after TBI, while levels of c-Rel were elevated significantly during the later phase of injury. Furthermore, TNF-α and IL-1β concentrations also showed a biphasic increase.

Conclusions: Biphasic activation of NF-κB could be induced after experimental TBI in rats. NF-κB p65 and c-Rel subunits were elevated at different post-TBI time periods, leading to a hypothesis that different NF-κB subunits might be involved in different pathophysiological processes after TBI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism
  • Brain Injuries / metabolism*
  • Cell Nucleus / metabolism
  • Interleukin-1beta / metabolism
  • Male
  • NF-kappa B / metabolism*
  • Protein Subunits / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Interleukin-1beta
  • NF-kappa B
  • Protein Subunits
  • Tumor Necrosis Factor-alpha