title: Activation of the high-mobility group box 1 protein-receptor for advanced glycation end-products signaling pathway in rats during neurogenesis after intracerebral hemorrhage.
abstract: OBJECTIVE
  Following intracerebral hemorrhage (ICH), high-mobility group box 1 protein (HMGB1) may promote neurogenesis that supports functional recovery. How HMGB1 regulates or participates in this process is unclear, as are the pattern recognition receptors and signaling pathways involved.
  
  
  METHODS
  ICH was induced by injection of collagenase in Sprague-Dawley rats, which were treated 3 days later with saline, with the HMGB1 inhibitor ethyl pyruvate or with FPS-ZM1, an antagonist of the receptor for advanced glycation end-products. A Sham group was treated with saline solution instead of collagenase and then treated 3 days later with saline again or with ethyl pyruvate or N-benzyl-4-chloro-N-cyclohexylbenzamide (FPS-ZM1). Expression of the following proteins was measured by Western blot, immunohistochemistry, or immunofluorescence: HMGB1, receptor for advanced glycation end-products, toll-like receptor (TLR)-2, TLR4, brain-derived neurotrophic factor, and matrix metalloproteinase-9. The number of cells positive for 5-bromo-2-deoxyuridine or doublecortin was determined by immunohistochemistry and immunofluorescence.
  
  
  RESULTS
  Levels of HMGB1, receptor for advanced glycation end-products, TLR4, TLR2, brain-derived neurotrophic factor, and matrix metalloproteinase-9 were significantly higher 14 days after ICH than at baseline, as were the numbers of 5-bromo-2-deoxyuridine- or doublecortin-positive cells. At the same time, HMGB1 moved from the nucleus into the cytoplasm. Administering ethyl pyruvate significantly reduced all these ICH-induced increases, except the increase in TLR4 and TLR2. Administering FPS-ZM1 reduced the ICH-induced increases in the expression of brain-derived neurotrophic factor and matrix metalloproteinase-9 and in the numbers of 5-bromo-2-deoxyuridine- or doublecortin-positive cells.
  
  
  CONCLUSIONS
  These findings suggest that HMGB1 acts via the receptor for advanced glycation end-products signaling pathway to promote neurogenesis in later phases of ICH.
authors.affiliation: From the Stroke Clinical Research Unit, Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People's Republic of China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Lei
authors.affiliation: From the Stroke Clinical Research Unit, Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People's Republic of China. dragonwbtxf@hotmail.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Wu
authors.affiliation: From the Stroke Clinical Research Unit, Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People's Republic of China.
authors.forename: Tian
authors.initials: T
authors.lastname: Cao
authors.affiliation: From the Stroke Clinical Research Unit, Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People's Republic of China.
authors.forename: Shuting
authors.initials: S
authors.lastname: Zhang
authors.affiliation: From the Stroke Clinical Research Unit, Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
mesh_terms: D000818:Animals; D002543:Cerebral Hemorrhage / Q000378:metabolism* / Q000473:pathology; D000089662:Doublecortin Protein; D024243:HMGB1 Protein / Q000096:biosynthesis*; D008297:Male; D055495:Neurogenesis / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic
keywords: advanced glycosylation end-product receptor; box protein 1, high mobility group; intracerebral hemorrhage; neurogenesis