Attenuation of acute and chronic damage following traumatic brain injury in copper, zinc-superoxide dismutase transgenic mice.
To elucidate the role of oxygen-derived free radicals and superoxide dismutase in traumatic brain injury (TBI), blood-brain barrier (BBB) permeability, brain edema, behavioral function, and necrotic cavity volume (CV) were evaluated after TBI using nontransgenic (nTg) mice and heterozygous and homozygous transgenic (Tg) mice with a 1.5- (Tg 1.5x), 3.1-(Tg3.1x) and five- (Tg5x) fold increase in human copper, zinc-superoxide dismutase (CuZn-SOD) activity. Traumatic brain injury was produced by the weight-drop method. Evans blue dye leakage 4 hours after injury was attenuated in a CuZn-SOD dose-dependent manner with decreases of 18.6%, 40.9%, and 48.8%, in the Tg1.5x, Tg3.1x, and Tg5x groups, respectively. The water content 6 hours after injury in the Tg3.1x (79.64%) and Tg5x (79.45%) groups was significantly lower than in nTg mice (81.37%). There was an initial decrease in body weight and in motor performance, as measured by beam walk and beam balance tasks undertaken 1 day after TBI. However, the average reduction in beam balance and beam walk performance deficits and changes in body weight postinjury were significantly ameliorated in Tg mice. The CV was significantly smaller in Tg mice than in nTg mice (p < 0.01). These results indicate that superoxide radicals play a deleterious role following TBI. Furthermore, Tg mice provide a useful model for demonstrating the beneficial role of an antioxidant enzyme in TBI without the confounding effect of pharmacokinetics, toxicity, and BBB permeability associated with exogenous agents.
Department of Neurological Surgery, School of Medicine, University of California, San Francisco, USA.
S
S
Mikawa
H
H
Kinouchi
H
H
Kamii
G T
GT
Gobbel
S F
SF
Chen
E
E
Carlson
C J
CJ
Epstein
P H
PH
Chan
D000818:Animals; D001930:Brain Injuries / Q000378:metabolism*; D005609:Free Radicals / Q000378:metabolism; D006651:Histocytochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D013482:Superoxide Dismutase / Q000378:metabolism*
D005609:Free Radicals; D013482:Superoxide Dismutase