Details

Autor(en) / Beteiligte

• Langhauser, Friederike
• Kraft, Peter
• Göb, Eva
• Leinweber, Jonas
• Schuhmann, Michael K
• Lorenz, Kristina
• Gelderblom, Mathias
• Bittner, Stefan
• Meuth, Sven G
• Wiendl, Heinz
• Magnus, Tim
• Kleinschnitz, Christoph

Titel

Blocking of α4 Integrin Does Not Protect From Acute Ischemic Stroke in Mice

Ist Teil von

• Stroke (1970), 2014-06, Vol.45 (6), p.1799-1806

Ort / Verlag

Hagerstown, MD: American Heart Association, Inc

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• BACKGROUND AND PURPOSE—T lymphocytes have recently been identified as key mediators of tissue damage in ischemic stroke. The interaction between very late antigen-4 (VLA-4) and vascular adhesion molecule-1 is crucial for the transvascular egress of T lymphocytes, and inhibition of this interaction by specific antibodies is a powerful strategy to combat autoimmune neuroinflammation. However, whether pharmacological blocking of T-lymphocyte trafficking is also protective during brain ischemia is still unclear. We investigated the efficacy of a monoclonal antibody directed against VLA-4 in mouse models of ischemic stroke. METHODS—Transient and permanent middle cerebral artery occlusion was induced in male C57Bl/6 mice. Animals treated with a monoclonal anti-CD49d antibody (300 μg) 24 hours before or 3 hours after the onset of cerebral ischemia and stroke outcome, including infarct size, functional status, and mortality, were assessed between day 1 and day 7. The numbers of immune cells invading the ischemic brain were determined by immunocytochemistry and flow cytometry. RESULTS—Blocking of VLA-4 significantly reduced the invasion of T lymphocytes and neutrophils on day 5 after middle cerebral artery occlusion and inhibited the upregulation of vascular adhesion molecule-1. However, the anti-CD49d antibody failed to influence stroke outcome positively irrespective of the model or the time point investigated. CONCLUSIONS—Pharmacological inhibition of the VLA-4/vascular adhesion molecule-1 axis in experimental stroke was ineffective in our hands. Our results cast doubt on the effectiveness of anti-CD49d as a stroke treatment. Further translational studies should be performed before testing anti–VLA-4 antibodies in patients with stroke.