Glutathione peroxidase activity modulates recovery in the injured immature brain.
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.
Tsuru-Aoyagi
Kyoko
K
Department of Neurological Surgery, University of California-San Francisco, 521 Parnassus Avenue, San Francisco, CA 94143, USA.
Potts
Matthew B
MB
Trivedi
Alpa
A
Pfankuch
Timothy
T
Raber
Jacob
J
Wendland
Michael
M
Claus
Catherine P
CP
Koh
Seong-Eun
SE
Ferriero
Donna
D
Noble-Haeusslein
Linda J
LJ
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
D005452:Fluoresceins; D009930:Organic Chemicals; C435731:fluoro jade; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase