P2X7 receptor antagonism with Brilliant Blue G promotes functional recovery in spontaneous canine spinal cord injury: a preliminary study in a large animal model.

BACKGROUND

Secondary injury cascades critically influence neurological outcomes after severe spinal cord injury (SCI), yet effective disease-modifying pharmacological interventions remain lacking. Extracellular ATP-mediated activation of the P2X7 receptor is a key driver of post-traumatic neuroinflammation, glial activation, and progressive tissue loss. While P2X7 receptor antagonism improves functional recovery in experimental rodent models of SCI, its translational relevance in naturally occurring large-animal injury has not been established.

METHODS

We conducted a prospective, uncontrolled, exploratory observational study in client-owned dogs serving as a naturally occurring large-animal model of severe SCI. Twenty non-ambulatory dogs with cervical or thoracolumbar SCI whose owners declined surgical decompression received intravenous Brilliant Blue G (BBG), a selective P2X7 receptor antagonist, at 10 mg/kg/day for seven consecutive days. Neurological function was assessed longitudinally using deep pain perception testing and the modified Frankel scale. Magnetic resonance imaging (MRI) was performed in a subset of cases.

RESULTS

Consistent neurological improvement temporally associated with BBG administration was observed across the cohort during follow-up. Eighteen dogs (90%) regained independent ambulation within 5 days to 15 months (median, 4 weeks). Among dogs presenting with complete injury equivalents (modified Frankel grade 5), 13 of 14 (92.9%; 95% CI, 66.1-99.8%) achieved independent ambulation. In cases with follow-up MRI, substantial functional recovery occurred despite persistent spinal cord compression. No adverse events attributable to BBG were observed.

CONCLUSION

Systemic P2X7 receptor antagonism with BBG was feasible and well tolerated and was associated with substantial functional recovery in a naturally occurring large-animal model of severe SCI, even in the absence of surgical decompression. Although causality cannot be established in this uncontrolled study, the consistency of recovery patterns and the observation of improvement despite persistent mechanical compression support further investigation of P2X7 receptor inhibition as a disease-modifying therapeutic strategy for acute human SCI.