BLOOD GLUTAMATE SCAVENGING AS A NEUROPROTECTIVE APPROACH IN NEUROTRAUMA

Neurotrauma, including traumatic brain injury (TBI), initiates secondary injury cascades in which glutamate-mediated excitotoxicity is one of the main contributors to progressive neuronal loss and long-term cognitive and functional deficits. This study evaluated the efficacy of combined blood–glutamate scavenging (cBGS) as a systemic strategy to reduce excitotoxicity, limit secondary damage, and improve recovery following moderate to severe experimental TBI. Adult mice underwent controlled cortical impact and received either saline or cBGS for five consecutive days post-injury. Outcomes were assessed using T2-weighted MRI to quantify edema volume and lesion size, alongside behavioral tests of motor coordination and gait. cBGS-treated mice exhibited significantly reduced cerebral edema at 24 hours post-injury compared with saline controls (n = 16, p < 0.0001), followed by a significant reduction in lesion size at 1-week post-injury (n = 16, p = 0.0038). These imaging findings were supported by improved motor performance and fewer gait errors in cBGS-treated animals. Together, the results demonstrate that enhancing systemic glutamate clearance via cBGS confers rapid and robust neuroprotection after TBI, supporting its potential as a novel therapeutic strategy for mitigating secondary injury in neurotrauma. These findings highlight cBGS as a promising first-in-class emergency therapeutic strategy with potential to improve functional outcomes after severe neurotrauma.