Molecular mechanisms controlling leukocyte trafficking in the central nervous system (NEUROTRAFFICKING)

Starting date
October 1, 2010
Duration (months)
48
Managers or local contacts
Constantin Gabriela
Keyword
traffico leucocitario, neuroinfiammazione, neurodegenerazione

Multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) represent the prototype of autoimmune chronic inflammatory and neurodegenerative diseases of the central nervous system (CNS). Migration of activated T cells across the BBB 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 and alzheimer's disease. 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 inflammatory and neurodegenerative diseases 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 patterns and the mechanisms involved in the contacts with neural cells. 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 and neurodegenerative pathologies.

Sponsors:

Commissione Europea
Funds: assigned and managed by the department
Syllabus: EUROPA - Progetti Europei
Commissione europea – VII PQ
Funds: assigned and managed by the department
Syllabus: EUROPA - Progetti Europei

Project participants

Stefano Angiari
Simona Luciana Budui
Gabriela Constantin
Full Professor
Vittorina Della Bianca
Assistant Professor
Elena Moscardo
Barbara Rossi
Assistant Professor
Elena Zenaro
Research Scholarship Holders
Publications
Title Authors Year
Human adipose-derived mesenchymal stem cells systemically injected promote peripheral nerve regeneration in the mouse model of sciatic crush. Marconi S.;Castiglione G.;Turano E.;Bissolotti G.;Angiari S;Farinazzo A.;Constantin G.;Bedogni G.;Bedogni A.;Bonetti B. 2012
Inverse agonism of cannabinoid CB1 receptor blocks the adhesion of encephalitogenic T cells in inflamed brain venules by a protein kinase A-dependent mechanism Rossi B; Zenaro E; Angiari S; Ottoboni L; Bach S; Piccio L; Pietronigro EC; Scarpini E; Fusco M; Leon A; Constantin G 2011
Transmigration of effector T lymphocytes: changing the rules Constantin G; Laudanna C 2011
Vascular inflammation in central nervous system diseases: adhesion receptors controlling leukocyte-endothelial interactions Rossi B; Angiari S; Zenaro E; Budui SL; Constantin G 2011

Activities

Research facilities