THROMBIN MAY CONTRIBUTE TO THE PATHOPHYSIOLOGY OF CENTRAL-NERVOUS-SYSTEM INJURY

Thrombin has multiple functions, including its function as a key enzym e during blood coagulation and other physiologic activities. We studie d brain tissue reactions to thrombin that might be present in the cent ral nervous system (CNS) following injury. Thrombin and three differen t types of controls-buffer, albumin, and plasmin-were individually inf used into the rat caudate nucleus by a continuous osmotic mini-pump. B rains were examined by conventional histologic and immunohistologic te chniques. Antibodies for bromodeoxyuridine (BrdU), glial fibrillary ac idic 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 nu mber of inflammatory cells, number of BrdU-positive cells, area and nu mber of vimentin-positive astrocytes, and the area of GFAP-positive as trocytes 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 i nflammation, scar formation, and reactive gliosis in the CNS following injury. These results suggest that thrombin may play an important rol e in inflammatory responses to CNS injury since thrombin is one of the blood borne factors that may interact with brain tissue after CNS inj ury. The data further suggest that the therapeutic application of anti thrombin agents for CNS injury suppresses inflammation and the excessi ve gliosis and scar formation, which are barriers to neuronal regenera tion.