Neuroprotective effects of cobalt oxide nanoparticles through mitigating oxidative stress and reactive glial responses in traumatic brain injury

Traumatic brain injury (TBI) is a leading global cause of mortality and long-term neurological deficits. TBI involves primary mechanical damage and secondary injury processes, including oxidative stress and reactive glial responses. Oxidative stress, driven by excessive reactive oxygen species (ROS), exacerbates neuronal damage, causing cellular apoptosis and prolonged inflammation. Traditional antioxidants have limited efficacy due to poor bioavailability and targeting. Nanotechnology-based antioxidants offer a promising alternative due to their intrinsic antioxidative activities. In the present study, we explored the neuroprotective effects of dimercaptosuccinic acid-coated cobalt oxide nanoparticles (Co₃O₄ NPs) in a mouse TBI model. Co₃O₄ NPs significantly reduced oxidative stress, neuronal death, brain tissue loss, and reactive glial activation, thereby enhancing long-term motor function recovery. Mechanistically, Co₃O₄ NPs lowered neuronal ROS levels. Co₃O₄ NPs also decreased astrocytic NOX2 expression, mitigating reactive glial responses. These findings suggest that Co₃O₄ NPs might offer therapeutic potential for TBI.