title: Biphasic activation of nuclear factor kappa B and expression of p65 and c-Rel after traumatic brain injury in rats.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu Province, People's Republic of China.
authors.forename: Yang-Chun
authors.initials: YC
authors.lastname: Hu
authors.forename: Qing
authors.initials: Q
authors.lastname: Sun
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Ding-Ding
authors.initials: DD
authors.lastname: Zhang
authors.forename: Biao
authors.initials: B
authors.lastname: Ma
authors.forename: Song
authors.initials: S
authors.lastname: Li
authors.forename: Wei-De
authors.initials: WD
authors.lastname: Li
authors.forename: Meng-Liang
authors.initials: ML
authors.lastname: Zhou
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Hang
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D001930:Brain Injuries / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D016328:NF-kappa B; D021122:Protein Subunits; D014409:Tumor Necrosis Factor-alpha