HIRUDIN SUPPRESSES THE INVASION OF INFLAMMATORY CELLS AND THE APPEARANCE OF VIMENTIN-POSITIVE ASTROCYTES IN THE RAT CEREBRAL ABLATION MODEL

Hirudin is a specific and direct-acting thrombin inhibitor superior to heparin as an anticoagulant. Thrombin is a multifunctional molecule t hat acts as a serine protease locally generated from prothrombin durin g blood coagulation related to injury and/or inflammation. We previous ly reported that thrombin might be involved in the inflammatory respon se, glial reaction, and scar formation that occurred in central nervou s system (CNS). Here we studied the suppressive effects of hirudin on the inflammation, vimentin-positive astrocytes, and glial fibrillary a cidic protein (GFAP)-positive astrocytes using rat cerebral ablation m odels. Hirudin and vehicle solution soaked in Gelform (R) were adminis tered to the cavity of the traumatic brain defect. Brains were examine d by conventional histologic and immunohistologic technique. Antibodie s for monocytes/macrophages, GFAP, and vimentin were used to assess th e infiltration of inflammatory cells and reaction of astrocytes. The n umber of the inflammatory cells, vimentin-positive astrocytes, and GFA P-positive astrocytes were quantitatively analyzed. Hirudin suppressed the infiltration of inflammatory cells and the increase in vimentin-p ositive astrocytes, but had no effects on the increase in GFAP-positiv e astrocytes. These data suggest that thrombin may play an important r ole in inflammatory and glial responses to CNS injury, and that hirudi n can be a candidate for the therapeutic agent that minimizes the seco ndary brain damage following the inflammation, and the glial reaction mediated by vimentin-positive astrocytes near the lesion site.