title: Glutathione peroxidase activity modulates recovery in the injured immature brain.
abstract: OBJECTIVE
  Mice subjected to traumatic brain injury at postnatal day 21 show emerging cognitive deficits that coincide with hippocampal neuronal loss. Here we consider glutathione peroxidase (GPx) activity as a determinant of recovery in the injured immature brain.
  
  
  METHODS
  Wild-type and transgenic (GPxTg) mice overexpressing GPx were subjected to traumatic brain injury or sham surgery at postnatal day 21. Animals were killed acutely (3 or 24 hours after injury) to assess oxidative stress and cell injury in the hippocampus or 4 months after injury after behavioral assessments.
  
  
  RESULTS
  In the acutely injured brains, a reduction in oxidative stress markers including nitrotyrosine was seen in the injured GPxTg group relative to wild-type control mice. In contrast, cell injury, with marked vulnerability in the dentate gyrus, was apparent despite no differences between genotypes. Magnetic resonance imaging demonstrated an emerging cortical lesion during brain maturation that was also indistinguishable between injured genotypes. Stereological analyses of cortical volumes likewise confirmed no genotypic differences between injured groups. However, behavioral tests beginning 3 months after injury demonstrated improved spatial memory learning in the GPxTg group. Moreover, stereological analysis within hippocampal subregions demonstrated a significantly greater number of neurons within the dentate of the GPx group.
  
  
  CONCLUSIONS
  Our results implicate GPx in recovery of spatial memory after traumatic brain injury. This recovery may be attributed, in part, to a reduction in early oxidative stress and selective, long-term sparing of neurons in the dentate.
authors.affiliation: Department of Neurological Surgery, University of California-San Francisco, 521 Parnassus Avenue, San Francisco, CA 94143, USA.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Tsuru-Aoyagi
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Potts
authors.forename: Alpa
authors.initials: A
authors.lastname: Trivedi
authors.forename: Timothy
authors.initials: T
authors.lastname: Pfankuch
authors.forename: Jacob
authors.initials: J
authors.lastname: Raber
authors.forename: Michael
authors.initials: M
authors.lastname: Wendland
authors.forename: Catherine P
authors.initials: CP
authors.lastname: Claus
authors.forename: Seong-Eun
authors.initials: SE
authors.lastname: Koh
authors.forename: Donna
authors.initials: D
authors.lastname: Ferriero
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Noble-Haeusslein
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D001930:Brain Injuries / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D005452:Fluoresceins; D005786:Gene Expression Regulation / Q000235:genetics; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology; D020287:In Situ Nick-End Labeling / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009930:Organic Chemicals; D018384:Oxidative Stress / Q000235:genetics; D020127:Recovery of Function / Q000502:physiology*; D013238:Stereotaxic Techniques; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D005452:Fluoresceins; D009930:Organic Chemicals; C435731:fluoro jade; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase