Following a traumatic brain injury (TBI), excess reactive oxygen species (ROS) and lipid peroxidation products (LPOx) are generated and lead to secondary injury beyond the primary insult. A major limitation of current treatments is poor target engagement, which has prevented success in clinical trials. Thus, nanoparticle-based treatments have received recent attention because of their ability to increase accumulation and retention in damaged brain. Theranostic neuroprotective copolymers (NPC3) containing thiol functional groups can neutralize ROS and LPOx. Immediate administration of NPC3 following injury in a controlled cortical impact (CCI) mouse model provides a therapeutic window in reducing ROS levels at 2.08–20.83 mg kg−1 in males and 5.52–27.62 mg kg−1 in females. This NPC3-mediated reduction in oxidative stress improves spatial learning and memory in males, while females show minimal improvement. Notably, NPC3-mediated reduction in oxidative stress prevents the bilateral spread of necrosis in male mice, which is not observed in female mice and likely accounts for the sex-based spatial learning and memory differences. Overall, these findings suggest sex-based differences to oxidative stress scavenger nanoparticle treatments, and a possible upper threshold of antioxidant activity that provides therapeutic benefit in injured brain since female mice benefit from NPC3 treatment to a lesser extent than male mice.
A. W. Tarudji et al., "Antioxidant Theranostic Copolymer-Mediated Reduction In Oxidative Stress Following Traumatic Brain Injury Improves Outcome In A Mouse Model," Advanced Therapeutics, Wiley Open Access, Jan 2023.
The definitive version is available at https://doi.org/10.1002/adtp.202300147
Materials Science and Engineering
Keywords and Phrases
barnes maze; lipid peroxidation products; reactive oxygen species; spatial learning and memory; thiol functionalized nanoparticles
International Standard Serial Number (ISSN)
Article - Journal
© 2023 The Authors, All rights reserved.
01 Jan 2023