Pivotal role for beta-1 integrin in neurovascular remodelling after ischemic stroke

    Authors

    J. D. Lathia; S. Chigurupati; J. Thundyil; P. K. Selvaraj; M. R. Mughal; T. M. Woodruff; S. L. Chan; V. T. Karamyan; M. P. Mattson;T. V. Arumugam

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    Abbreviated Journal Title

    Exp. Neurol.

    Keywords

    beta 1 integrin; Cerebral ischemia; Angiogenesis; Vascular remodelling; Endothelial cells; ENDOTHELIAL GROWTH-FACTOR; CEREBRAL-ARTERY OCCLUSION; BLOOD-BRAIN-BARRIER; ENHANCES ANGIOGENESIS; FACTOR EXPRESSION; CELL-ADHESION; INTEGRINS; MICE; RAT; ANGIOPOIETIN-1; Neurosciences

    Abstract

    beta 1 integrin is a cell surface molecule that is critical for endothelial cell adhesion, migration and survival during angiogenesis. In the present study we employed in vivo and in vitro models to elucidate the role of beta 1 integrin in vascular remodelling and stroke outcomes. At 24 h after cerebral ischemia and reperfusion (I/R), the ischemic cortex (ipsilateral area) exhibited modest beta 1 integrin immunoreactivity and a robust increase was observed at 72 h. Double-label immunohistochemical analysis for beta 1 integrin with neuronal (NeuN). microglial (Iba-1), astrocyte (GFAP), progenitor cell (Ng2) and blood vessel (collagen 4) markers showed that beta 1 integrin expression only localized to blood vessels. In vitro studies using cultured endothelial cells and a beta 1 integrin blocking antibody confirmed that beta 1 integrin is required for endothelial cell migration, proliferation and blood vessel formation. In vivo studies in the cerebral I/R model using the beta 1 integrin blocking antibody further confirmed that beta 1 integrin signaling is involved in vascular formation and recovery following ischemic stroke. Finally, we found that beta 1 integrin is critically involved in functional deficits and survival after a stroke. These results Suggest that beta 1 integrin plays important roles in neurovascular remodelling and functional outcomes following stroke, and that targeting the beta 1 integrin signalling may provide a novel strategy for modulating angiogenesis in ischemic stroke and other pathological conditions. (C) 2009 Elsevier Inc. All rights reserved.

    Journal Title

    Experimental Neurology

    Volume

    221

    Issue/Number

    1

    Publication Date

    1-1-2010

    Document Type

    Article

    Language

    English

    First Page

    107

    Last Page

    114

    WOS Identifier

    WOS:000273827500013

    ISSN

    0014-4886

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