title: Functional role of soluble receptor for advanced glycation end products in stroke.
abstract: OBJECTIVE
  Little is known about the involvement of the soluble form of receptor for advanced glycation end products (sRAGE) in acute ischemic stroke (IS). Here, we aim to identify the role of plasma sRAGE and high mobility group box 1 (HMGB1) in imaging-confirmed IS patients, as well as mice subjected to focal ischemic stroke.
  
  
  RESULTS
  IS patients were recruited and plasma samples were collected for the measurement of sRAGE and HMGB1 after stroke. The relation of sRAGE and HMGB1 with acute IS was also investigated in a C57BL/6J mouse model of focal ischemic stroke and primary cortical neurons subjected to oxygen and glucose deprivation. Plasma levels of sRAGE and HMGB1 were both significantly increased within 48 hours after IS, and the sRAGE level was an independent predictor of functional outcome at 3 months poststroke. Immunoprecipitation assays revealed that the binding of plasma HMGB1 to sRAGE increased progressively after IS both in patients and mice. Administration of recombinant sRAGE significantly reduced infiltrating immune cells and improved the outcome of injury in mice, protected cultured neurons against oxygen and glucose deprivation-induced cell death, and ameliorated the detrimental effect of recombinant HMGB1.
  
  
  CONCLUSIONS
  Early poststroke plasma sRAGE may play a protective role in IS by capturing HMGB1. Hence, recombinant sRAGE is a potential therapeutic agent in acute IS.
authors.affiliation: Stroke Center and Department of Neurology, National Taiwan University Hospital, Hospital, Taipei, Taiwan.
authors.forename: Sung-Chun
authors.initials: SC
authors.lastname: Tang
authors.forename: Yu-Chi
authors.initials: YC
authors.lastname: Wang
authors.forename: Yu-I
authors.initials: YI
authors.lastname: Li
authors.forename: Hsiao-Ching
authors.initials: HC
authors.lastname: Lin
authors.forename: Silvia
authors.initials: S
authors.lastname: Manzanero
authors.forename: Yu-Hsuan
authors.initials: YH
authors.lastname: Hsieh
authors.forename: Simon
authors.initials: S
authors.lastname: Phipps
authors.forename: Chaur-Jong
authors.initials: CJ
authors.lastname: Hu
authors.forename: Hung-Yi
authors.initials: HY
authors.lastname: Chiou
authors.forename: Yi-Shuian
authors.initials: YS
authors.lastname: Huang
authors.forename: Wei-Shiung
authors.initials: WS
authors.lastname: Yang
authors.forename: Mark P
authors.initials: MP
authors.lastname: Mattson
authors.forename: Thiruma V
authors.initials: TV
authors.lastname: Arumugam
authors.forename: Jiann-Shing
authors.initials: JS
authors.lastname: Jeng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016923:Cell Death; D015687:Cell Hypoxia; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016009:Chi-Square Distribution; D004195:Disease Models, Animal; D005260:Female; D005947:Glucose / Q000172:deficiency; D024243:HMGB1 Protein / Q000097:blood; D006801:Humans; D047468:Immunoprecipitation; D020244:Infarction, Middle Cerebral Artery / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy; D016015:Logistic Models; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage; D010100:Oxygen / Q000378:metabolism; D011379:Prognosis; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000008:administration & dosage / Q000097:blood* / Q000172:deficiency / Q000235:genetics; D012307:Risk Factors; D020521:Stroke / Q000097:blood* / Q000175:diagnosis; D000071939:Stroke Rehabilitation; D013624:Taiwan; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D024243:HMGB1 Protein; D018696:Neuroprotective Agents; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D005947:Glucose; D010100:Oxygen