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

Abstract

Blood vessel loss and inflammation cause secondary degeneration following spinal cord injury. Angiopoietin-1 through the Tie2 receptor, and other ligands through alphavbeta3 integrin, promote endothelial cell survival during developmental or tumour angiogenesis. Here, daily intravenous injections with an alphavbeta3-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 alphavbeta3 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.

• Authors: Shu Han, Sheila A Arnold, Srinivas D Sithu, Edward T Mahoney, Justin T Geralds, Phuong Tran, Richard L Benton, Melissa A Maddie, Stanley E D'Souza, Scott R Whittemore, Theo Hagg
• Journal: Brain : a journal of neurology (Brain) Vol. 133 Issue Pt 4 Pg. 1026-42 (Apr 2010) ISSN: 1460-2156 [Electronic] England
• PMID: 20375135 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Angiopoietin-1
• Integrin alphaVbeta3
• Neuroprotective Agents
• Peptide Fragments

Topics

• Amino Acid Sequence
• Angiopoietin-1 (administration & dosage)
• Animals
• Cell Movement (drug effects, physiology)
• Drug Therapy, Combination
• Female
• Humans
• Injections, Intravenous
• Integrin alphaVbeta3 (administration & dosage)
• Mice
• Mice, Inbred C57BL
• Molecular Sequence Data
• Neuroprotective Agents (administration & dosage)
• Peptide Fragments (administration & dosage)
• Recovery of Function (drug effects, physiology)
• Spinal Cord (blood supply, drug effects)
• Spinal Cord Injuries (physiopathology, prevention & control)
• Thoracic Vertebrae
• Time Factors