title: Cerium Oxide Nanoparticles Improve Outcome afterIn VitroandIn VivoMild Traumatic Brain Injury.
abstract: Mild traumatic brain injury results in aberrant free radical generation, which is associated with oxidative stress, secondary injury signaling cascades, mitochondrial dysfunction, and poor functional outcome. Pharmacological targeting of free radicals with antioxidants has been examined as an approach to treatment, but has met with limited success in clinical trials. Conventional antioxidants that are currently available scavenge a single free radical before they are destroyed in the process. Here, we report for the first time that a novel regenerative cerium oxide nanoparticle antioxidant reduces neuronal death and calcium dysregulation afterin vitrotrauma. Further, using anin vivomodel of mild lateral fluid percussion brain injury in the rat, we report that cerium oxide nanoparticles also preserve endogenous antioxidant systems, decrease macromolecular free radical damage, and improve cognitive function. Taken together, our results demonstrate that cerium oxide nanoparticles are a novel nanopharmaceutical with potential for mitigating neuropathological effects of mild traumatic brain injury and modifying the course of recovery.
authors.affiliation: Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, Virginia, USA.
authors.forename: Zachary S
authors.initials: ZS
authors.lastname: Bailey
authors.affiliation: Department of Pharmacology, Edward Via College of Osteopathic Medicine, Blacksburg, Virginia, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Nilson
authors.affiliation: Department of Pharmacology, Edward Via College of Osteopathic Medicine, Blacksburg, Virginia, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Bates
authors.affiliation: Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, Virginia, USA.
authors.forename: Adewole
authors.initials: A
authors.lastname: Oyalowo
authors.affiliation: Department of Pharmacology, Edward Via College of Osteopathic Medicine, Blacksburg, Virginia, USA.
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Hockey
authors.affiliation: Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, Virginia, USA.
authors.forename: Venkata Siva Sai Sujith
authors.initials: VSSS
authors.lastname: Sajja
authors.affiliation: Department of Pharmacology, Edward Via College of Osteopathic Medicine, Blacksburg, Virginia, USA.
authors.forename: Chevon
authors.initials: C
authors.lastname: Thorpe
authors.affiliation: Department of Pharmacology, Edward Via College of Osteopathic Medicine, Blacksburg, Virginia, USA.
authors.forename: Heidi
authors.initials: H
authors.lastname: Rogers
authors.affiliation: Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, Virginia, USA.
authors.forename: Bryce
authors.initials: B
authors.lastname: Dunn
authors.affiliation: Department of Pharmacology, Edward Via College of Osteopathic Medicine, Blacksburg, Virginia, USA.
authors.forename: Aaron S
authors.initials: AS
authors.lastname: Frey
authors.affiliation: Department of Pharmacology, Edward Via College of Osteopathic Medicine, Blacksburg, Virginia, USA.
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Billings
authors.affiliation: Department of Pharmacology, Edward Via College of Osteopathic Medicine, Blacksburg, Virginia, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Sholar
authors.affiliation: Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, Virginia, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Hermundstad
authors.affiliation: Integrated Mesoscale Architectures for Sustainable Catalysis, Rowland Institute of Science, Harvard University, Cambridge, Massachusetts, USA.
authors.forename: Challa
authors.initials: C
authors.lastname: Kumar
authors.affiliation: Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, Virginia, USA.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: VandeVord
authors.affiliation: Department of Pharmacology, Edward Via College of Osteopathic Medicine, Blacksburg, Virginia, USA.
authors.forename: Beverly A
authors.initials: BA
authors.lastname: Rzigalinski
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001924:Brain Concussion / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002563:Cerium / Q000008:administration & dosage*; D066298:In Vitro Techniques; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
chemical_list: D002563:Cerium; C030583:ceric oxide
keywords: cerium oxide; nanoparticles; oxidative stress; traumatic brain injury