Antioxidant Theranostic Copolymer‐Mediated Reduction in Oxidative Stress Following Traumatic Brain Injury Improves Outcome in a Mouse Model

Abstract Following a traumatic brain injury (TBI), excess reactive oxygen species (ROS) and lipid peroxidation products (LPOx) are generated lead to secondary beyond the primary insult. A major limitation of current treatments is poor target engagement, which has prevented success in clinical trials. Thus, nanoparticle‐based have received recent attention because their ability increase accumulation retention damaged brain. Theranostic neuroprotective copolymers (NPC3) containing thiol functional groups can neutralize ROS LPOx. Immediate administration NPC3 following controlled cortical impact (CCI) mouse model provides therapeutic window reducing levels at 2.08‐20.83 mg/kg males 5.52‐27.62 females. This NPC3‐mediated reduction oxidative stress improves spatial learning memory males, while females show minimal improvement. Notably, prevents bilateral spread necrosis male mice, was not observed female mice likely accounts for sex‐based differences. Overall, these findings suggest differences scavenger nanoparticle treatments, possible upper threshold antioxidant activity that benefit injured since from treatment lesser extent than mice. article protected by copyright. All rights reserved