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Updated: Jun 11, 2025
Synergetic Use of Neural Precursor Cells and Self-assembling Peptides in Experimental Cervical Spinal Cord Injury
Published on: February 23, 2015
Adenosine triphosphate release inhibitors targeting pannexin1 improve recovery after spinal cord injury
Kazuaki Morishita1, Hiroaki Nakashima1, Masaaki Machino1
1Department of Orthopedics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Abstract:
Traumatic spinal cord injury is characterized by immediate and irreversible tissue loss at the lesion site and secondary tissue damage. Secondary injuries should, in principle, be preventable, although no effective treatment options currently exist for patients with acute spinal cord injury. Traumatized tissues release excessive amounts of adenosine triphosphate and activate the P2X purinoceptor 7/pannexin1 complex, which is associated with secondary injury. We investigated the neuroprotective effects of the blue dye Brilliant Blue FCF, a selective inhibitor of P2X purinoceptor 7/pannexin1 that is approved for use as a food coloring, by comparing it with Brilliant Blue G, a P2X7 purinoceptor antagonist, and carbenoxolone, which attenuates P2X purinoceptor 7/pannexin1 function, in a rat spinal cord injury model. Brilliant Blue FCF administered early after spinal cord injury reduced spinal cord anatomical damage and improved motor recovery without apparent toxicity. Brilliant Blue G had the highest effect on this neurological recovery, with Brilliant Blue FCF and carbenoxolone having comparable improvement. Furthermore, Brilliant Blue FCF administration reduced local astrocytic and microglial activation and neutrophil infiltration, and no differences in these histological effects were observed between compounds. Thus, Brilliant Blue FCF protects spinal cord neurons after spinal cord injury and suppresses local inflammatory responses as well as Brilliant Blue G and carbenoxolone.
Insights
Brilliant Blue FCF, a food dye, shows neuroprotective effects against spinal cord injury by inhibiting the P2X7/pannexin1 complex. It reduces damage and improves motor function, similar to other tested compounds.
Area of Science:
- Neuroscience
- Pharmacology
- Regenerative Medicine
Background:
- Traumatic spinal cord injury (SCI) causes immediate tissue loss and secondary damage, with no current effective treatments for acute SCI.
- The P2X purinoceptor 7 (P2X7)/pannexin1 complex, activated by adenosine triphosphate released from traumatized tissues, contributes significantly to secondary SCI.
- Identifying novel therapeutic targets for SCI is crucial for improving patient outcomes.
Purpose of the Study:
- To investigate the neuroprotective potential of Brilliant Blue FCF, a P2X7/pannexin1 inhibitor and food dye, in a rat SCI model.
- To compare the efficacy of Brilliant Blue FCF with Brilliant Blue G (a P2X7 antagonist) and carbenoxolone (a P2X7/pannexin1 inhibitor).
- To evaluate the effects of these compounds on anatomical damage, motor recovery, and inflammatory responses post-SCI.
Main Methods:
- A rat model of traumatic spinal cord injury was utilized.
- Rats were treated with Brilliant Blue FCF, Brilliant Blue G, or carbenoxolone shortly after SCI.
- Outcomes assessed included spinal cord anatomical integrity, motor function recovery, and histological analysis of inflammatory markers (astrocytic activation, microglial activation, neutrophil infiltration).
Main Results:
- Brilliant Blue FCF administration reduced anatomical damage and improved motor recovery in SCI rats, with no observed toxicity.
- Brilliant Blue G demonstrated the most significant effect on neurological recovery, while Brilliant Blue FCF and carbenoxolone showed comparable improvements.
- All tested compounds effectively reduced astrocytic and microglial activation and neutrophil infiltration at the injury site.
Conclusions:
- Brilliant Blue FCF demonstrates significant neuroprotective effects in acute spinal cord injury, comparable to established P2X7/pannexin1 inhibitors.
- The food-approved dye Brilliant Blue FCF represents a potential therapeutic agent for mitigating secondary damage and promoting recovery after SCI.
- Inhibition of the P2X7/pannexin1 complex is a viable strategy for reducing inflammation and improving neurological outcomes in spinal cord injury.
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