Cellular and molecular basis of neuroinflamation: potential targets for translational medicine and therapy

Although considered detrimental, inflammation may also have beneficial actions on the central nervous system (CNS), particularly in repair and recovery. Therefore, it is important to take into account the overall balance of neuroinflammatory mediators after injury, since it may have a profound impact on the outcome. This project will focus to highlight some cellular and molecular mechanisms which underlie neuroinflammation, to identify potential target molecules and to test the efficacy of several therapeutic approaches (purine nucleoside analogues, hyperbaric oxygenation, B vitamins) in suppression of detrimental and enhancement of beneficial inflammatory mechanisms. Considering pivotal role of extracellular purine nucleotides and nucleosides in the control of neurodegenerative processes and inflammatory responses a particular focus will be put on regulation of their metabolism. In animal models (brain injury, experimental autoimmune encephalomyelitis, cuprizone-induced demyelination) behavioral, cellular and molecular approaches will be used to study neuroinflammation-induced pathogenesis. The main goal of the project is to identify, characterize and standardize potential early and sensitive biomarkers of neuroinflammation and neurodegeneration that can be used in clinical and laboratory practice for diagnosis and prognosis of patient outcome and treatment efficacy.