Publications

Authors:

P.F. Fabene, G. Navarro Mora, M. Martinello, B. Rossi, F. Merigo, L. Ottoboni, S. Bach, S. Angiari, D. Benati, A. Chakir, L. Zanetti, F. Schio, A. Osculati, P. Marzola, E. Nicolato, J.W.Homeister, L. Xia, J.B. Lowe, R.P. McEver, F. Osculati, A. Sbarbati, E.C. Butcher, G. Constantin

Title:

A role for leukocyte-endothelial adhesion mechanism in epilepsy

Year:

2008

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Nations of authors:

STATI UNITI D'AMERICA; ITALIA

Language:

Inglese

Format:

Elettronico

Referee:

No

Name of journal:

Nature Medicine

ISSN of journal:

1078-8956

N° Volume:

14

Number or Folder:

12

Page numbers:

1377-1383

Code PMID:

19029985

Keyword:

epilepsy, inflammation, mouse

Short description of contents:

The mechanisms involved in the pathogenesis of epilepsy, a chronic neurological disorder that affects approximately one percent of the world population, are not well understood. Using a mouse model of epilepsy, we show that seizures induce elevated expression of vascular cell adhesion molecules and enhanced leukocyte rolling and arrest in brain vessels mediated by the leukocyte mucin P-selectin glycoprotein ligand-1 (PSGL-1, encoded by Selplg) and leukocyte integrins alpha(4)beta(1) and alpha(L)beta(2). Inhibition of leukocyte-vascular interactions, either with blocking antibodies or by genetically interfering with PSGL-1 function in mice, markedly reduced seizures. Treatment with blocking antibodies after acute seizures prevented the development of epilepsy. Neutrophil depletion also inhibited acute seizure induction and chronic spontaneous recurrent seizures. Blood-brain barrier (BBB) leakage, which is known to enhance neuronal excitability, was induced by acute seizure activity but was prevented by blockade of leukocyte-vascular adhesion, suggesting a pathogenetic link between leukocyte-vascular interactions, BBB damage and seizure generation. Consistent with the potential leukocyte involvement in epilepsy in humans, leukocytes were more abundant in brains of individuals with epilepsy than in controls. Our results suggest leukocyte-endothelial interaction as a potential target for the prevention and treatment of epilepsy.

Web page:

www.pubmed.com

Product ID:

48759

Handle IRIS:

11562/-327364

Deposited On:

February 16, 2009

Last Modified:

February 16, 2009

Bibliographic citation:

P.F. Fabene, G. Navarro Mora, M. Martinello, B. Rossi, F. Merigo, L. Ottoboni, S. Bach, S. Angiari, D. Benati, A. Chakir, L. Zanetti, F. Schio, A. Osculati, P. Marzola, E. Nicolato, J.W.Homeister, L. Xia, J.B. Lowe, R.P. McEver, F. Osculati, A. Sbarbati, E.C. Butcher, G. Constantin, A role for leukocyte-endothelial adhesion mechanism in epilepsy «Nature Medicine» , vol. 14 , n. 12 , 2008 , pp. 1377-1383

Consulta la scheda completa presente nel repository istituzionale della Ricerca di Ateneo