title: Thrombin-triggered angiogenesis in rat brains following experimental intracerebral hemorrhage.
abstract: OBJECTIVE
  Angiogenesis occurs after intracerebral hemorrhage (ICH). Thrombin mediates mitogenesis and survival in endothelial cells and induces angiogenesis. The present study aimed to clarify whether thrombin is involved in triggering ICH-related angiogenesis.
  
  
  METHODS
  In the first part of the experiment, autologous blood (with or without hirudin) was injected to induce ICH. In the second part, rats received either 1 U (50 μl) thrombin or 50 μl 0.9% sterile saline. In both parts, 5-bromo-2-deoxyuridine (BrdU) was administered intraperitoneally. Brains were perfused to identify BrdU-positive/von Willebrand factor (vWF)-positive nuclei. The expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1) and Ang-2 was evaluated by immunohistochemistry and quantitative real-time reverse transcription polymerase chain reaction.
  
  
  RESULTS
  After ICH, the number of BrdU-/vWF-positive nuclei increased until Day 14, and vessels positive for HIF-1α, VEGF, Ang-1, and Ang-2 were observed around the clot. Quantitative analysis showed that ICH upregulated expression of HIF-1α, VEGF, Ang-1, and Ang-2 notably compared with that in sham controls (p < 0.05). However, hirudin significantly inhibited these effects. After thrombin treatment, many BrdU-positive/vWF-positive nuclei and HIF-1α-, VEGF-, Ang-1- and Ang-2-positive vessels could be detected around the affected region.
  
  
  CONCLUSIONS
  Thrombin can induce angiogenesis in rat brains and may be an important trigger for ICH-related angiogenesis.
authors.affiliation: Institute of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Hua-Jun
authors.initials: HJ
authors.lastname: Zhou
authors.forename: Tao
authors.initials: T
authors.lastname: Tang
authors.forename: Han-Jin
authors.initials: HJ
authors.lastname: Cui
authors.forename: A-Li
authors.initials: AL
authors.lastname: Yang
authors.forename: Jie-Kun
authors.initials: JK
authors.lastname: Luo
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lin
authors.forename: Qi-Dong
authors.initials: QD
authors.lastname: Yang
authors.forename: Xing-Qun
authors.initials: XQ
authors.lastname: Li
mesh_terms: D042683:Angiopoietin-1 / Q000096:biosynthesis; D042702:Angiopoietin-2 / Q000096:biosynthesis; D000818:Animals; D001921:Brain / Q000098:blood supply; D002196:Capillaries / Q000473:pathology; D002452:Cell Count; D002543:Cerebral Hemorrhage / Q000473:pathology*; D005455:Fluorescent Antibody Technique; D006490:Hemostatics / Q000494:pharmacology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis; D007150:Immunohistochemistry; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D013917:Thrombin / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2; D006490:Hemostatics; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D013917:Thrombin