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

Exp Neurol. 2010 Jan;221(1):107-14. doi: 10.1016/j.expneurol.2009.10.007. Epub 2009 Oct 21.

Abstract

beta1 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 beta1 integrin in vascular remodelling and stroke outcomes. At 24 h after cerebral ischemia and reperfusion (I/R), the ischemic cortex (ipsilateral area) exhibited modest beta1 integrin immunoreactivity and a robust increase was observed at 72 h. Double-label immunohistochemical analysis for beta1 integrin with neuronal (NeuN), microglial (Iba-1), astrocyte (GFAP), progenitor cell (Ng2) and blood vessel (collagen 4) markers showed that beta1 integrin expression only localized to blood vessels. In vitro studies using cultured endothelial cells and a beta1 integrin blocking antibody confirmed that beta1 integrin is required for endothelial cell migration, proliferation and blood vessel formation. In vivo studies in the cerebral I/R model using the beta1 integrin blocking antibody further confirmed that beta1 integrin signaling is involved in vascular formation and recovery following ischemic stroke. Finally, we found that beta1 integrin is critically involved in functional deficits and survival after a stroke. These results suggest that beta1 integrin plays important roles in neurovascular remodelling and functional outcomes following stroke, and that targeting the beta1 integrin signalling may provide a novel strategy for modulating angiogenesis in ischemic stroke and other pathological conditions.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • Antibodies / therapeutic use
  • Antigens / metabolism
  • Blood Vessels / metabolism*
  • Brain / pathology
  • Calcium-Binding Proteins / metabolism
  • Cell Line
  • Cell Movement / drug effects
  • Cell Movement / physiology
  • Cell Proliferation / drug effects
  • Cell Proliferation / ethics
  • Collagen / metabolism
  • Disease Models, Animal
  • Endothelial Cells / drug effects
  • Endothelial Cells / physiology
  • Gene Expression Regulation / physiology*
  • Glial Fibrillary Acidic Protein / metabolism
  • Infarction, Middle Cerebral Artery / drug therapy
  • Infarction, Middle Cerebral Artery / metabolism*
  • Infarction, Middle Cerebral Artery / pathology
  • Infarction, Middle Cerebral Artery / physiopathology*
  • Interferon-beta / immunology
  • Interferon-beta / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microfilament Proteins
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / metabolism*
  • Phosphopyruvate Hydratase / metabolism
  • Proteoglycans / metabolism
  • Reperfusion Injury / drug therapy
  • Reperfusion Injury / metabolism
  • Statistics, Nonparametric

Substances

  • Aif1 protein, mouse
  • Antibodies
  • Antigens
  • Calcium-Binding Proteins
  • Glial Fibrillary Acidic Protein
  • Microfilament Proteins
  • Proteoglycans
  • chondroitin sulfate proteoglycan 4
  • Interferon-beta
  • Collagen
  • Phosphopyruvate Hydratase