The pathophysiology of cerebral cortical lesions in multiple sclerosis (MS) is not understood. We investigated cerebral cortex microvessels during immune-mediated demyelination in the MS model chronic murine experimental autoimmune encephalomyelitis (EAE) by immunolocalization of the endothelial cell tight junction (TJ) integral proteins claudin-5 and occludin, a structural protein of caveolae, caveolin-1, and the blood-brain barrier-specific endothelial transporter, Glut 1. In EAE-affected mice, there were areas of extensivesubpial demyelination and well-demarcated lesions that extended to deeper cortical layers. Activation of microglia and absence of perivascular inflammatory infiltrates were common in these areas. Microvascular endothelial cells showed increased expression of caveolin-1 and a coincident loss of both claudin-5 and occludin normal junctional staining patterns. At a very early disease stage, claudin-5 molecules tended to cluster and form vacuoles that were also Glut 1 positive; the initially preserved occludin pattern became diffusely cytoplasmic at more advanced stages. Possible internalization of claudin-5 on TJ dismantling was suggested by its coexpression with the autophagosomal marker MAP1LC3A. Loss of TJ integrity was confirmed by fluorescein isothiocyanate- dextran experimentsthat showed leakage of the tracer into the perivascular neuropil. These observations indicate that, in the cerebral cortex of EAE-affected mice, there is a microvascular disease that differentially targets claudin-5 and occludin during ongoing demyelination despite only minimal inflammation. Copyright © 2012 by the American Association of Neuropathologists, Inc.

Blood-brain barrier alterations in the cerebral cortex in experimental autoimmune encephalomyelitis / Errede, Mariella; Girolamo, Francesco; Ferrara, Giovanni; Strippoli, Maurizio; Morando, Sara; Boldrin, Valentina; Rizzi, Marco; Uccelli, Antonio; Perris, Roberto; Bendotti, Caterina; Salmona, Mario; Roncali, Luisa; Virgintino, Daniela. - In: JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY. - ISSN 0022-3069. - 71:10(2012), pp. 840-854. [10.1097/NEN.0b013e31826ac110]

Blood-brain barrier alterations in the cerebral cortex in experimental autoimmune encephalomyelitis

FERRARA, GIOVANNI;PERRIS, Roberto;
2012

Abstract

The pathophysiology of cerebral cortical lesions in multiple sclerosis (MS) is not understood. We investigated cerebral cortex microvessels during immune-mediated demyelination in the MS model chronic murine experimental autoimmune encephalomyelitis (EAE) by immunolocalization of the endothelial cell tight junction (TJ) integral proteins claudin-5 and occludin, a structural protein of caveolae, caveolin-1, and the blood-brain barrier-specific endothelial transporter, Glut 1. In EAE-affected mice, there were areas of extensivesubpial demyelination and well-demarcated lesions that extended to deeper cortical layers. Activation of microglia and absence of perivascular inflammatory infiltrates were common in these areas. Microvascular endothelial cells showed increased expression of caveolin-1 and a coincident loss of both claudin-5 and occludin normal junctional staining patterns. At a very early disease stage, claudin-5 molecules tended to cluster and form vacuoles that were also Glut 1 positive; the initially preserved occludin pattern became diffusely cytoplasmic at more advanced stages. Possible internalization of claudin-5 on TJ dismantling was suggested by its coexpression with the autophagosomal marker MAP1LC3A. Loss of TJ integrity was confirmed by fluorescein isothiocyanate- dextran experimentsthat showed leakage of the tracer into the perivascular neuropil. These observations indicate that, in the cerebral cortex of EAE-affected mice, there is a microvascular disease that differentially targets claudin-5 and occludin during ongoing demyelination despite only minimal inflammation. Copyright © 2012 by the American Association of Neuropathologists, Inc.
Blood-brain barrier alterations in the cerebral cortex in experimental autoimmune encephalomyelitis / Errede, Mariella; Girolamo, Francesco; Ferrara, Giovanni; Strippoli, Maurizio; Morando, Sara; Boldrin, Valentina; Rizzi, Marco; Uccelli, Antonio; Perris, Roberto; Bendotti, Caterina; Salmona, Mario; Roncali, Luisa; Virgintino, Daniela. - In: JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY. - ISSN 0022-3069. - 71:10(2012), pp. 840-854. [10.1097/NEN.0b013e31826ac110]
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11381/2813161
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