Thrombin May Contribute to the Pathophysiology of Central Nervous System Injury

Thrombin has multiple functions, including its function as a key enzyme during blood coagulation and other physiologic activities. We studied brain tissue reactions to thrombin that might be present in the central nervous system (CNS) following injury. Thrombin and three different types of controls—buffer, albumin, and plasmin—were individually infused into the rat caudate nucleus by a continuous osmotic mini-pump. Brains were examined by conventional histologic and immunohistologic techniques. Antibodies for bromodeoxyuridine (BrdU), glial fibrillary acidic protein (GFAP), vimentin, and laminin were employed to assess the infiltration of inflammatory cells, proliferation activity of cells, and reaction of astrocytes and mesenchymal cells, respectively. The number of inflammatory cells, number of BrdU-positive cells, area and number of vimentin-positive astrocytes, and the area of GFAP-positive astrocytes were quantitatively analyzed. Thrombin caused infiltration of inflammatory cells, proliferation of mesenchymal cells, induction of angiogenesis, and an increase in vimentin-positive reactive astrocytes. These histologic changes caused by thrombin infusion resembled the inflammation, scar formation, and reactive gliosis in the CNS following injury. These results suggest that thrombin may play an important role in inflammatory responses to CNS injury since thrombin is one of the blood borne factors that may interact with brain tissue after CNS injury. The data further suggest that the therapeutic application of antithrombin agents for CNS injury suppresses inflammation and the excessive gliosis and scar formation, which are barriers to neuronal regeneration.