Antioxidant Thioether Core-Crosslinked Nanoparticles Prevent the Bilateral Spread of Secondary Injury to Protect Spatial Learning and Memory in a Controlled Cortical Impact Mouse Model of Traumatic Brain Injury
Abstract
The secondary phase of traumatic brain injury (TBI) is partly caused by the release of excess reactive oxygen species (ROS) from the primary injury. However, there are currently no therapies that have been shown to reduce the secondary spread of injury beyond the primary insult. Nanoparticles offer the ability to rapidly accumulate and be retained in injured brain for improved target engagement. Here, we utilized systemically administered antioxidant thioether core-cross-linked nanoparticles (NP1) that scavenge and inactivate ROS to reduce this secondary spread of injury in a mild controlled cortical impact (CCI) mouse model of TBI. We found that NP1 treatment protected CCI mice from injury induced learning and memory deficits observed in the Morris water maze (MWM) test at 1-month post-CCI. This protection was likely a result of NP1-mediated reduction in oxidative stress in the ipsilateral hemisphere as determined by immunofluorescence imaging of markers of oxidative stress and the spread of neuroinflammation into the contralateral hippocampus as determined by immunofluorescence imaging of activated microglia and neuron-astrocyte-microglia triad formation. These data suggest NP1-mediated reduction in post-traumatic oxidative stress correlates with the reduction in the spread of injury to the contralateral hippocampus to protect spatial memory and learning in CCI mice. Therefore, these materials may offer an improved treatment strategy to reduce the secondary spread of TBI.
Recommended Citation
A. W. Tarudji et al., "Antioxidant Thioether Core-Crosslinked Nanoparticles Prevent the Bilateral Spread of Secondary Injury to Protect Spatial Learning and Memory in a Controlled Cortical Impact Mouse Model of Traumatic Brain Injury," Biomaterials, vol. 272, Elsevier, May 2021.
The definitive version is available at https://doi.org/10.1016/j.biomaterials.2021.120766
Department(s)
Materials Science and Engineering
Keywords and Phrases
Morris Water Maze; Nanomedicine; Neuroinflammation; Reactive Oxygen Species; Traumatic Brain Injury
International Standard Serial Number (ISSN)
0142-9612
Document Type
Article - Journal
Document Version
Citation
File Type
text
Language(s)
English
Rights
© 2021 Elsevier, All rights reserved.
Publication Date
01 May 2021
PubMed ID
33819812
