1. Systemic administration of an antagonist of the ATP-sensitive receptor P2X7 improves recovery after spinal cord injury.
- Author
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Peng W, Cotrina ML, Han X, Yu H, Bekar L, Blum L, Takano T, Tian GF, Goldman SA, and Nedergaard M
- Subjects
- Animals, Disease Models, Animal, Humans, Indicators and Reagents administration & dosage, Indicators and Reagents pharmacology, Neuroprotective Agents administration & dosage, Neuroprotective Agents pharmacology, Rats, Rats, Sprague-Dawley, Receptors, Purinergic P2 metabolism, Receptors, Purinergic P2X7, Recovery of Function drug effects, Rosaniline Dyes administration & dosage, Spinal Cord drug effects, Spinal Cord metabolism, Spinal Cord pathology, Spinal Cord Injuries physiopathology, Time Factors, Adenosine Triphosphate metabolism, Purinergic P2 Receptor Antagonists, Rosaniline Dyes pharmacology, Spinal Cord Injuries prevention & control
- 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.
- Published
- 2009
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