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.

CONCLUSION:

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: Roberto Anaya-Prado, Nahum Pérez-Gomez, Luis H Toledo-Pereyra, John Walsh, Jackie Jordan, Peter A Ward
• Journal: The Journal of trauma (J Trauma) Vol. 65 Issue 3 Pg. 678-84 (Sep 2008) ISSN: 1529-8809 [Electronic] United States
• PMID: 18784584 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biphenyl Compounds
• Cell Adhesion Molecules
• Mannosides
• bimosiamose disodium
• Peroxidase
• Mannose

Topics

• Animals
• Biphenyl Compounds (therapeutic use)
• Brain Ischemia (drug therapy, enzymology, pathology)
• Cell Adhesion Molecules (antagonists & inhibitors)
• Disease Models, Animal
• Male
• Mannose (analogs & derivatives)
• Mannosides (therapeutic use)
• Neutrophil Infiltration
• Peroxidase (metabolism)
• Rats
• Rats, Sprague-Dawley
• Shock, Hemorrhagic (drug therapy, enzymology, pathology)