The hemostatic system in canine neurologystudy of the fibrinolytic activity in cerebrospinal fluid in neurological disorders and evaluation of tissue factor expression, fibrin/fibrinogen deposition and fibrinolysis in canine gliomas

Resumo

Veterinary neurology is one of the most evolving areas in veterinary medicine. Recent medical advances and the greater demand from society to face neurological disorders in veterinary patients have contributed to a better understanding of the underlying mechanisms of neurological diseases in pets. Despite this, the etiologic origin of some diseases still remains obscure, and diagnostic and therapeutic approaches are limited in some cases, so research is needed to solve these problems. Studies in human beings have demonstrated the relationship between the hemostatic system and the inflammatory response as well as the influence of hemostatic system molecules in cancer biology. Neither the activation of the hemostatic system as part of canine brain tumor pathophysiology, nor the intrathecal fibrinolytic activity in dogs with neurologic disorders had been previously studied. D-dimers are specific cross-linked fibrin degradation products and their presence confirms previous coagulation system activation. Previous studies in human beings and animals demonstrated that local fibrinolytic activity can be measured by means of D-dimer concentrations in different biological fluids. In this direction, this PhD thesis confirmed that intrathecal fibrinolytic activity is activated in some canine neurologic disorders, independently of systemic fibrinolytic activity. A significant rise in cerebrospinal fluid D-dimer concentration occurs in dogs with steroid responsive meningitis-arteritis, suggesting that CSF D-dimer concentrations might be potential diagnostic markers of this disease. This PhD thesis also addressed the relationship between the hemostatic system and canine glioma biology and demonstrated that canine gliomas overexpress tissue factor, the extrinsic pathway activator of the coagulation cascade, and that there is intratumoral activation of the coagulation and fibrinolytic systems. In conclusion, the results of this PhD thesis confirm that the hemostatic system is involved in the pathophysiology of some canine central nervous system diseases and provide a new perspective to perform further research, especially on inflammatory and neoplastic disorders of the canine central nervous system.