REDUCTION OF BRAIN INJURY USING HEPARIN TO INHIBIT LEUKOCYTE ACCUMULATION IN A RAT MODEL OF TRANSIENT FOCAL CEREBRAL-ISCHEMIA .1. PROTECTIVE MECHANISM

Heparin has long been established as an anticoagulant. Although hepari n has been demonstrated to reduce brain injury after ischemia and repe rfusion, its mechanism of action remains unknown. Recent investigation s reveal that it can modulate biological processes such as binding to adhesion receptors on endothelial cells and leukocytes. The authors hy pothesized that heparin's protective effect is closely related to its antileukocyte adherence property. They evaluated the efficacy of sulfa ted polysaccharides (unfractionated heparin, low-molecular-weight hepa rin, heparan sulfate, chondroitin sulfate C, and dextran sulfate) on l eukocyte accumulation, infarction size,and neurological outcome after transient focal cerebral ischemia in rats subjected to 1 hour of ische mia and 48 hours of reperfusion. Forty-nine animals were included in t he study. The animals receiving unfractionated heparin or dextran sulf ate 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 unfractiona ted heparin also showed significantly better results than the animals receiving an equivalent anticoagulant dose of low-molecular-weight hep arin. These data indicate that heparin's antileukocyte property plays a more important role than its anticoagulant ability in neuronal prote ction. 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 a s a therapeutic agent for ischemia and reperfusion injury by the preve ntion of leukocyte accumulation, the results also serve as a basis for studying important cellular and molecular events that contribute tiss ue damage.