Core-Cross-Linked Nanoparticles Reduce Neuroinflammation and Improve Outcome in a Mouse Model of Traumatic Brain Injury
| Autor: | Abby M. Kelly, Dasom Yoo, Alexander W. Magsam, Forrest M. Kievit, Anthony J. Convertine, Patrick S. Stayton |
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| Rok vydání: | 2017 |
| Předmět: |
Materials science
Traumatic brain injury Polysorbates General Physics and Astronomy Hippocampus Nanoparticle 02 engineering and technology Sulfides Pharmacology 010402 general chemistry 01 natural sciences Antioxidants Article Mice Brain Injuries Traumatic medicine Animals General Materials Science Neuroinflammation Inflammation chemistry.chemical_classification Reactive oxygen species General Engineering Brain 021001 nanoscience & nanotechnology medicine.disease 0104 chemical sciences Mice Inbred C57BL Disease Models Animal Oxidative Stress Nanomedicine RAW 264.7 Cells chemistry Gliosis Nanoparticles medicine.symptom Reactive Oxygen Species 0210 nano-technology |
| Zdroj: | ACS Nano |
| ISSN: | 1936-086X 1936-0851 |
| Popis: | Traumatic brain injury (TBI) is the leading cause of death and disability in children and young adults, yet there are currently no treatments available that prevent the secondary spread of damage beyond the initial insult. The chronic progression of this secondary injury is in part caused by the release of reactive oxygen species (ROS) into surrounding normal brain. Thus, treatments that can enter the brain and reduce the spread of ROS should improve outcome from TBI. Here a highly versatile, reproducible, and scalable method to synthesize core-cross-linked nanoparticles (NPs) from polysorbate 80 (PS80) using a combination of thiol–ene and thiol–Michael chemistry is described. The resultant NPs consist of a ROS-reactive thioether cross-linked core stabilized in aqueous solution by hydroxy-functional oligoethylene oxide segments. These NPs show narrow molecular weight distributions and have a high proportion of thioether units that reduce local levels of ROS. In a controlled cortical impact mouse model of TBI, the NPs are able to rapidly accumulate and be retained in damaged brain as visualized through fluorescence imaging, reduce neuroinflammation and the secondary spread of injury as determined through magnetic resonance imaging and histopathology, and improve functional outcome as determined through behavioral analyses. Our findings provide strong evidence that these NPs may, upon further development and testing, provide a useful strategy to help improve the outcome of patients following a TBI. |
| Databáze: | OpenAIRE |
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