title: Dietary Docosahexaenoic Acid Improves Cognitive Function, Tissue Sparing, and Magnetic Resonance Imaging Indices of Edema and White Matter Injury in the Immature Rat after Traumatic Brain Injury.
abstract: Traumatic brain injury (TBI) is the leading cause of acquired neurologic disability in children. Specific therapies to treat acute TBI are lacking. Cognitive impairment from TBI may be blunted by decreasing inflammation and oxidative damage after injury. Docosahexaenoic acid (DHA) decreases cognitive impairment, oxidative stress, and white matter injury in adult rats after TBI. Effects of DHA on cognitive outcome, oxidative stress, and white matter injury in the developing rat after experimental TBI are unknown. We hypothesized that DHA would decrease early inflammatory markers and oxidative stress, and improve cognitive, imaging and histologic outcomes in rat pups after controlled cortical impact (CCI). CCI or sham surgery was delivered to 17 d old male rat pups exposed to DHA or standard diet for the duration of the experiments. DHA was introduced into the dam diet the day before CCI to allow timely DHA delivery to the pre-weanling pups. Inflammatory cytokines and nitrates/nitrites were measured in the injured brains at post-injury Day (PID) 1 and PID2. Morris water maze (MWM) testing was performed at PID41-PID47. T2-weighted and diffusion tensor imaging studies were obtained at PID12 and PID28. Tissue sparing was calculated histologically at PID3 and PID50. DHA did not adversely affect rat survival or weight gain. DHA acutely decreased oxidative stress and increased anti-inflammatory interleukin 10 in CCI brains. DHA improved MWM performance and lesion volume late after injury. At PID12, DHA decreased T2-imaging measures of cerebral edema and decreased radial diffusivity, an index of white matter injury. DHA improved short- and long-term neurologic outcomes after CCI in the rat pup. Given its favorable safety profile, DHA is a promising candidate therapy for pediatric TBI. Further studies are needed to explore neuroprotective mechanisms of DHA after developmental TBI.
authors.affiliation: 1 Department of Pediatrics, Division of Critical Care, University of Utah , Salt Lake City, Utah.
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Schober
authors.affiliation: 1 Department of Pediatrics, Division of Critical Care, University of Utah , Salt Lake City, Utah.
authors.forename: Daniela F
authors.initials: DF
authors.lastname: Requena
authors.affiliation: 2 Department of Bioengineering, University of Utah , Salt Lake City, Utah.
authors.forename: Osama M
authors.initials: OM
authors.lastname: Abdullah
authors.affiliation: 1 Department of Pediatrics, Division of Critical Care, University of Utah , Salt Lake City, Utah.
authors.forename: T Charles
authors.initials: TC
authors.lastname: Casper
authors.affiliation: 3 Department of Pediatrics, Division of Neonatology, University of Utah , Salt Lake City, Utah.
authors.forename: Joanna
authors.initials: J
authors.lastname: Beachy
authors.affiliation: 3 Department of Pediatrics, Division of Neonatology, University of Utah , Salt Lake City, Utah.
authors.forename: Daniel
authors.initials: D
authors.lastname: Malleske
authors.affiliation: 4 College of Pharmacy and Spinal Cord and Brain Injury Research Center, University of Kentucky , Lexington, Kentucky.
authors.forename: James R
authors.initials: JR
authors.lastname: Pauly
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000188:drug therapy* / Q000473:pathology; D000070642:Brain Injuries, Traumatic / Q000188:drug therapy* / Q000473:pathology; D060825:Cognitive Dysfunction / Q000188:drug therapy* / Q000473:pathology; D056324:Diffusion Tensor Imaging / Q000379:methods; D004281:Docosahexaenoic Acids / Q000008:administration & dosage*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D066127:White Matter / Q000187:drug effects* / Q000473:pathology
chemical_list: D004281:Docosahexaenoic Acids
keywords: DTI; Morris water maze; controlled cortical impact; pediatric