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↵1 W.P. and M.L.C. contributed equally to this work.
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Edited by Pasko Rakic, Yale University School of Medicine, New Haven, CT, and approved June 11, 2009 (received for review March 6, 2009)
Abstract
Traumatic spinal cord injury is characterized by an immediate, irreversible loss of tissue at the lesion site, as well as a secondary expansion of tissue damage over time. Although secondary injury should, in principle, be preventable, no effective treatment options currently exist for patients with acute spinal cord injury (SCI). Excessive release of ATP by the traumatized tissue, followed by activation of high-affinity P2X7 receptors, has previously been implicated in secondary injury, but no clinically relevant strategy by which to antagonize P2X7 receptors has yet, to the best of our knowledge, been reported. Here we have tested the neuroprotective effects of a systemically administered P2X7R antagonist, Brilliant blue G (BBG), in a weight-drop model of thoracic SCI in rats. Administration of BBG 15 min after injury reduced spinal cord anatomic damage and improved motor recovery without evident toxicity. Moreover, BBG treatment directly reduced local activation of astrocytes and microglia, as well as neutrophil infiltration. These observations suggest that BBG not only protected spinal cord neurons from purinergic excitotoxicity, but also reduced local inflammatory responses. Importantly, BBG is a derivative of a commonly used blue food color (FD&C blue No. 1), which crosses the blood–brain barrier. Systemic administration of BBG may thus comprise a readily feasible approach by which to treat traumatic SCI in humans.
Footnotes
- 2To whom correspondence may be addressed at: Department of Neurology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 645, Rochester, NY 14642. E-mail: steven_goldman{at}urmc.rochester.edu
- 3To whom correspondence may be addressed at: Division of Glial Disease and Therapeutics, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642. E-mail: nedergaard{at}urmc.rochester.edu
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Author contributions: T.T., S.A.G., and M.N. designed research; W.P., X.H., H.Y., and L. Bekar performed research; W.P., M.L.C., L. Blum, T.T., and G.-F.T. analyzed data; and M.L.C., S.A.G., and M.N. wrote the paper.
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Edited by Pasko Rakic, Yale University School of Medicine, New Haven, CT, and approved June 11, 2009
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
Systemic administration of an antagonist of the ATP-sensitive receptor P2X7 improves recovery after spinal cord injury
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