NEUROTRAFFICKING · Molecular mechanisms controlling leukocyte trafficking in the central nervous system

Multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) represent the prototype of autoimmune chronic inflammatory diseases of the central nervous system (CNS). Migration of activated T cells across the blood-brain barrier represents a critical step in the pathogenesis of MS and EAE, and inhibition of lymphocyte trafficking in the CNS represents a powerful therapeutic approach in MS patients as well as in animal models of this disease.In recent years growing evidence show that immune cells and inflammation mechanisms play an unexpected role in other neurological diseases such as epilepsy. Our team has recently shown that seizures induce vascular inflammation and enhanced neutrophil and T cell adhesion in brain vessels. Inhibition of leukocyte-vascular interactions dramatically reduced seizures in an experimental model of epilepsy, suggesting leukocyte-endothelial interaction as a potential target for the prevention and treatment of epilepsy.The main goal of this project is to study the mechanisms controlling immune cell trafficking in neurological diseases such as MS and epilepsy in which inflammation has a detrimental role. We will first study novel molecular mechanisms controlling leukocyte-endothelial interactions in CNS microcirculation taking advantage of our established expertise in intravital microscopy studies. Leukocyte trafficking will be further followed inside CNS parenchyma by using two-photon microscopy, which will allow us to characterize leukocyte migration Overall, NEUROTRAFFICKING will generate fundamental knowledge to the understanding of the role of immune system in neurological disease and will unveil novel potential therapeutic targets for CNS inflammatory pathologies.