Publications

A role for leukocyte-endothelial adhesion mechanism in epilepsy  (2008)

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. 122008pp. 1377-1383

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