Nanocatalytic Neuroprotection and Neurological Recovery Post-Traumatic Brain Injury.

Traumatic brain injury (TBI) is a severe neurological disorder requiring novel therapeutic strategies. We developed ultrasmall catalytic Ce0.7Zr0.3O2 nanozymes (CZs) and investigated their neuroprotective potential in combination with nimodipine, a calcium channel blocker. CZs effectively alleviated oxidative stress but were insufficient against calcium-mediated neuronal injury, while nimodipine alone inadequately mitigated oxidative damage. Combined therapy preserved blood-brain barrier integrity, reduced oxidative stress and neuroinflammation, and inhibited neuronal apoptosis, with CZs exerting potent effects even at low doses. Nimodipine synergistically regulated calcium overload, suppressed CaMKII activation, and enhanced functional recovery during later TBI stages. Notably, nimodipine promoted preferential accumulation of CZs in injured brain tissue, further amplifying neuroprotection. Behavioral and histological analyses confirmed significant improvements in cognitive and motor outcomes, indicating superior efficacy of the combined treatment over either agent alone. These findings highlight a promising strategy integrating nanozyme-based antioxidative therapy with calcium channel blockade for comprehensive TBI management, offering translational potential for clinical application.