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Year: 2010  |  Volume: 133  |  Issue: 4  |  Page No.: 1026 - 1042

Rescuing vasculature with intravenous angiopoietin-1 and {alpha}v{beta}3 integrin peptide is protective after spinal cord injury

S Han, S. A Arnold, S. D Sithu, E. T Mahoney, J. T Geralds, P Tran, R. L Benton, M. A Maddie, S. E D'Souza, S. R Whittemore and T. Hagg    


Blood vessel loss and inflammation cause secondary degeneration following spinal cord injury. Angiopoietin-1 through the Tie2 receptor, and other ligands through vβ3 integrin, promote endothelial cell survival during developmental or tumour angiogenesis. Here, daily intravenous injections with an vβ3-binding peptide named C16 or an angiopoietin-1 mimetic following a spinal cord contusion at thoracic level 9 in mice rescued epicentre blood vessels, white matter and locomotor function, and reduced detrimental inflammation. Preserved vascularity and reduced inflammation correlated with improved outcomes. C16 and angiopoietin-1 reduced leukocyte transmigration in vitro. Growth factor receptors and integrins facilitate each others’ function. Therefore, angiopoietin-1 and C16 were combined and the effects were additive, resulting in almost complete functional recovery. The treatment had lasting effects when started 4 h following injury and terminated after one week. These results identify vβ3 integrin and the endothelial-selective angiopoietin-1 as vascular and inflammatory regulators that can be targeted in a clinically relevant manner for neuroprotection after central nervous system trauma.

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