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

Data inizio
1 ottobre 2010
Durata (mesi) 
48
Responsabili (o referenti locali)
Constantin Gabriela
Parole chiave
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.

Enti finanziatori:

Commissione Europea
Finanziamento: assegnato e gestito dal Dipartimento
Programma: EUROPA - Progetti Europei
Commissione europea – VII PQ
Finanziamento: assegnato e gestito dal Dipartimento
Programma: EUROPA - Progetti Europei

Partecipanti al progetto

Pubblicazioni
Titolo Autori Anno
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

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