title: Expression of HMGB1 and RAGE in rat and human brains after traumatic brain injury.
abstract: BACKGROUND
  Increasing evidence suggests that an inflammatory reaction contributes to the secondary brain injury that plays a critical role in the clinical outcome of patients with traumatic brain injury (TBI). Recently, high-mobility group box 1 (HMGB1) has been identified as a key cytokine in the inflammatory reaction and may represent a new target for the treatment of TBI. However, the expression of HMGB1 during this injury process has not yet been studied.
  
  
  METHODS
  In this study, the levels of both HMGB1 and receptor for advanced glycation end products (RAGE) in the rat brain were analyzed by Western blot at different time points after TBI. Immunohistochemistry was also performed to examine the expression pattern of HMGB1 and RAGE in both the rat and the human brain after TBI.
  
  
  RESULTS
  In the rat brain, HMGB1 levels significantly declined below the basal level at 6 hours after TBI and then gradually returned to the basal level 2 days later. RAGE expression increased 6 hours after TBI and reached its peak after 1 day; this level then slowly decreased but remained higher than the sham-injury group until 6 days after TBI. In both rat and human brains, HMGB1 either disappeared or was translocated from the nucleus to the cytoplasm at early stages after TBI and then was localized to the cytoplasm of phagocytic microglia at later stages. RAGE expression increased in the region surrounding the contused area after TBI in both rat and human brains. At later stages, RAGE was mainly expressed in microglia.
  
  
  CONCLUSIONS
  HMGB1 is involved in both early and later stages after TBI. Targeting HMGB1 signaling may be a promising therapeutic approach for the treatment of TBI.
authors.affiliation: Department of Forensic Medicine, Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Tie-Lei
authors.initials: TL
authors.lastname: Gao
authors.forename: Xiang-Tian
authors.initials: XT
authors.lastname: Yuan
authors.forename: Dan
authors.initials: D
authors.lastname: Yang
authors.forename: Hai-Li
authors.initials: HL
authors.lastname: Dai
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Wang
authors.forename: Xue
authors.initials: X
authors.lastname: Peng
authors.forename: Hong-Jiang
authors.initials: HJ
authors.lastname: Shao
authors.forename: Zhan-Feng
authors.initials: ZF
authors.lastname: Jin
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Fu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D017127:Glycation End Products, Advanced; D024243:HMGB1 Protein / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D015601:Injury Severity Score; D008297:Male; D008875:Middle Aged; D051381:Rats; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D017127:Glycation End Products, Advanced; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic