# Nanocatalytic Neuroprotection and Neurological Recovery Post‐Traumatic Brain Injury

## TL;DR

A new treatment combining nanozymes and nimodipine improves brain recovery after injury by reducing damage and boosting cognitive and motor functions.

## Contribution

Combining nanozymes with nimodipine offers a novel synergistic strategy for TBI treatment by targeting oxidative stress and calcium overload.

## Key findings

- Combined therapy preserved blood–brain barrier integrity and reduced oxidative stress and neuroinflammation.
- Nimodipine enhanced functional recovery by regulating calcium overload and suppressing CaMKII activation.
- Nanozymes showed potent effects even at low doses and were preferentially accumulated in injured brain tissue with nimodipine.

## Abstract

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.

This study demonstrates that combining Ce0.7Zr0.3O2 nanozymes with nimodipine enhances neuroprotection after traumatic brain injury. The therapy reduces oxidative stress, neuronal apoptosis, and improves blood–brain barrier integrity, with nanozymes effective at low doses. Nimodipine promotes targeted brain accumulation of nanozymes, highlighting a promising strategy integrating nanomaterials and calcium channel blockade for comprehensive TBI management.