Neuroinflammatory profile of rats subjected to a chronic cyclosporine treatment and possible neuroprotective action of guanosine

• Grant number: 10/52010-1
• Support Opportunities: Regular Research Grants
• Start date: January 01, 2011
• End date: December 31, 2012
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Cristoforo Scavone
• Grantee: Cristoforo Scavone
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cyclosporine (CsA) is an immunosuppressive agent frequently used in the clinic for prevention of allograft rejection and for the treatment of autoimmune diseases. Despite its desired action on the immune system, CsA treatment may present serious adverse effects. Previous resulte from our group demonstrated that chronic treatment with CsA causes endothelial damage associated with dyslipidemia and coagulatory disorders in Wistar rats, which are important mechanisms involved in the progressive obstructive vascular disease, common in patients under CsA treatment Moreover, CsA was able to alter parameters related to anxiety behavioral and brain oxidative stress in these animals. Neurotoxicity occurs in about 60% of patients undergoing CsA treatment, but the mechanisms underlying this process are poorly understood. The multiple confounding factors in clinical practice, including risk factors, previous genetic differences and immune response of patients make it difficult to determine the adverse effects specifically related to CsA treatment. Given the clinical importance of CsA and the few studies regarding mechanisms of neurotoxicity caused by its use, especially in neuroinflammation, this project aims to investigate the neuroinflammatory profile and possible alterations in biochemical parameters associated with neuroinflammation, and morphological changes of neural cells and cerebral vessels in rats subjected to chronic immunosuppressive therapy with CsA. Therefore, searching for therapeutic alternatives that could optimize the CsA immunosuppressive therapy, we intend to address the possible neuroprotective effect of guanosine against the neurotoxicity induced by CsA. (AU)