title: Reduction of brain injury using heparin to inhibit leukocyte accumulation in a rat model of transient focal cerebral ischemia. I. Protective mechanism.
abstract: Heparin has long been established as an anticoagulant. Although heparin has been demonstrated to reduce brain injury after ischemia and reperfusion, its mechanism of action remains unknown. Recent investigations reveal that it can modulate biological processes such as binding to adhesion receptors on endothelial cells and leukocytes. The authors hypothesized that heparin's protective effect is closely related to its antileukocyte adherence property. They evaluated the efficacy of sulfated polysaccharides (unfractionated heparin, low-molecular-weight heparin, heparan sulfate, chondroitin sulfate C, and dextran sulfate) on leukocyte accumulation, infarction size, and neurological outcome after transient focal cerebral ischemia in rats subjected to 1 hour of ischemia and 48 hours of reperfusion. Forty-nine animals were included in the study. The animals receiving unfractionated heparin or dextran sulfate showed a significant reduction in leukocyte accumulation, infarct size, and neurological dysfunction 48 hours after reperfusion (p < 0.05) when compared to untreated animals. The animals receiving unfractionated heparin also showed significantly better results than the animals receiving an equivalent anticoagulant dose of low-molecular-weight heparin. These data indicate that heparin's antileukocyte property plays a more important role than its anticoagulant ability in neuronal protection. The relative potency of the sulfated polysaccharides tested in leukocyte depletion was closely related to their degree of sulfation. Thus, in addition to demonstrating the potential efficacy of heparin as a therapeutic agent for ischemia and reperfusion injury by the prevention of leukocyte accumulation, the results also serve as a basis for studying important cellular and molecular events that contribute to tissue damage.
authors.affiliation: Department of Neurosurgery, University of Minnesota Medical School, Minneapolis, USA.
authors.forename: K
authors.initials: K
authors.lastname: Yanaka
authors.forename: S R
authors.initials: SR
authors.lastname: Spellman
authors.forename: J B
authors.initials: JB
authors.lastname: McCarthy
authors.forename: T R
authors.initials: TR
authors.lastname: Oegema
authors.forename: W C
authors.initials: WC
authors.lastname: Low
authors.forename: P J
authors.initials: PJ
authors.lastname: Camarata
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002809:Chondroitin Sulfates / Q000627:therapeutic use; D016264:Dextran Sulfate / Q000627:therapeutic use; D006493:Heparin / Q000627:therapeutic use*; D006497:Heparan Sulfate / Q000627:therapeutic use; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology*; D007962:Leukocytes / Q000201:enzymology / Q000473:pathology*; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control
chemical_list: D002809:Chondroitin Sulfates; D016264:Dextran Sulfate; D006493:Heparin; D006497:Heparan Sulfate; D009195:Peroxidase