title: High-mobility group box-1 and receptor for advanced glycation end products in preterm infants with brain injury.
abstract: BACKGROUND
  High-mobility group box-1 (HMGB1) protein acts as an important pro-infl ammatory mediator, which is capable of activating inflammation and tissue repair. HMGB1 can bind to its receptor such as advanced glycation end products (RAGE). RAGE, in turn, can promote the production of pro-inflammatory cytokines. Soluble RAGE (sRAGE) is a truncated form of the receptor comprising the extracellular domain of RAGE and can inhibit RAGE-activation. The objective of this study was to investigate whether HMGB1 and RAGE are involved in the development of brain injury in preterm infants.
  
  
  METHODS
  In total, 108 infants ≤34 weeks gestation at birth were divided into 3 groups according to cranial altrasound scan: mild brain damage (n=33), severe brain damage (n=8) and no brain damage (n=67). All the placentas were submitted for pathologic evaluation. Histological chorioamnionitis (HCA) was defined as neutrophil infi ltration of amniotic membranes, umbilical cord or chorionic plate. Expressions of HMGB1 and RAGE proteins were assessed by immunohistochemical analysis. The concentration of HMGB1 and sRAGE in umbilical cord blood were measured by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  The frequency of HCA was 30.12%. HCA was associated with elevated concentrations of HMGB1 and decreased sRAGE in umbilical cord blood. The severe brain injury group demonstrated higher cord blood HMGB1 concentrations (P<0.001) and lower sRAGE concentrations (P<0.001) than both other groups. Brain injury in the premature infants was linked to intense staining for HMGB1/RAGE, particularly in infl ammatory cells.
  
  
  CONCLUSIONS
  Changes of cord blood HMGB1 and sRAGE of premature infants had direct relationship with the degree of infl ammation and severity of brain damage. Monitoring sRAGE and HMGB1 levels may be helpful to predict intrauterine infection and brain injury in premature infants.
authors.affiliation: Department of Pediatrics, the Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang, China. lhy5154@163.com.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Lu
authors.affiliation: Department of Pediatrics, the Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang, China.
authors.forename: Jiang-Lin
authors.initials: JL
authors.lastname: Ma
authors.affiliation: Department of Pediatrics, the Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang, China.
authors.forename: Ji-Yan
authors.initials: JY
authors.lastname: Shan
authors.affiliation: Department of Pediatrics, the Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, the Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang, China.
authors.forename: Qiu-Xia
authors.initials: QX
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, the Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001930:Brain Injuries / Q000151:congenital* / Q000000981:diagnostic imaging / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D014463:Ultrasonography
chemical_list: D015415:Biomarkers; D017127:Glycation End Products, Advanced; D024243:HMGB1 Protein
keywords: HMGB1; RAGE; brain injury; preterm infants; sRAGE