title: Small molecule selectin inhibitor in global cerebral ischemia and controlled hemorrhagic shock.
abstract: BACKGROUND
  The clinical and experimental management of stroke has not reached the therapeutic success seen in other medical conditions associated with ischemia/reperfusion. In this work, we investigated the effect of a small molecule selectin inhibitor TBC-1269, in animals subjected to global cerebral ischemia (GCI) and controlled hemorrhagic shock (CHS).
  
  
  METHODS
  Forty-eight male Sprague-Dawley rats weighting between 275 g and 300 g were subjected to a model of GCI and CHS. Three groups of animals were included in this study (n = 16 per group): sham/saline (group 1); GCI/CHS/Saline (group 2); GCI/CHS/TBC-1269 (group 3). Experimental design consisted of bilateral carotid artery occlusion for 20 minutes, and the development of CHS until a mean arterial pressure of 50 mm Hg was reached. At 20 minutes, clamps were released, and resuscitation was achieved with normal saline, and the end point was to attain a mean arterial pressure of 80 mm Hg. Treatment at the beginning of resuscitation included either normal saline (groups 1 and 2) or TBC-1269 (25 mg/kg, group 3). The following indices were evaluated: brain tissue myeloperoxidase, average numbers of ischemic neurons, and 7-day survival.
  
  
  RESULTS
  Brain myeloperoxidase was decreased in animals treated with TBC-1269, although this difference was not statistically significant. Treated animals demonstrated a significant smaller amount of ischemic neurons than the controls. Survival was also improved from 40% in controls to 80% with TBC-1269 treatment. This difference was statistically significant.
  
  
  CONCLUSIONS
  The use of a small molecule selectin inhibitor, TBC-1269, had a protective effect in this model of GCI and CHS, as evidenced by decreased numbers of ischemic neurons and improved survival rates.
authors.affiliation: Borgess Research Institute, Michigan State University/Kalamazoo Center for Medical Studies, Kalamazoo, MI 49048, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Anaya-Prado
authors.forename: Nahum
authors.initials: N
authors.lastname: Pérez-Gomez
authors.forename: Luis H
authors.initials: LH
authors.lastname: Toledo-Pereyra
authors.forename: John
authors.initials: J
authors.lastname: Walsh
authors.forename: Jackie
authors.initials: J
authors.lastname: Jordan
authors.forename: Peter A
authors.initials: PA
authors.lastname: Ward
mesh_terms: D000818:Animals; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors; D004195:Disease Models, Animal; D008297:Male; D008358:Mannose / Q000031:analogs & derivatives; D008362:Mannosides / Q000627:therapeutic use*; D020556:Neutrophil Infiltration; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology
chemical_list: D001713:Biphenyl Compounds; D015815:Cell Adhesion Molecules; D008362:Mannosides; C108700:bimosiamose disodium; D009195:Peroxidase; D008358:Mannose