Transgenic mice and knockout mutants in the study of oxidative stress in brain injury.
A rapid increase in the need to explore the molecular basis of cellular function and injury in the central nervous system has led neuroscientists to employ transgenic mouse technology. The successful making of transgenic mice (Tg) overexpressing human CuZn-superoxide dismutase (SOD-1) activity has made it possible to investigate the role of oxygen free radicals in ischemic and traumatic brain injury in a molecular fashion. It has been demonstrated that the 3-fold increase in SOD-1 transgene activity in SOD-1 Tg mice offers protection against cerebral ischemia and reperfusion in two different models of focal cerebral ischemia, as compared to nontransgenic wild-type littermates. Studies involving traumatic brain injury have also demonstrated that acute injuries, including brain edema and blood-brain barrier permeability, are significantly reduced in SOD-1 Tg mice. Furthermore, chronic neurological deficits, such as beam walking, beam balance, and body weight, are significantly improved in these transgenic animals following traumatic brain injury. In addition to the SOD-1 Tg mice being a useful tool for the study of CNS injury, targeted disruption of the mouse gene for mitochondrial manganese SOD (SOD-2) has been successful. These SOD-2 knockout mutant mice, in addition to the recently developed knockout mutants of neuronal nitric oxide synthase (NOS), are believed to offer a unique opportunity to elucidate the oxidative mechanisms in brain injury following stroke and trauma.
Chan
P H
PH
Department of Neurology and Neurosurgery, University of California at San Francisco 94143-0651, USA.
Epstein
C J
CJ
Li
Y
Y
Huang
T T
TT
Carlson
E
E
Kinouchi
H
H
Yang
G
G
Kamii
H
H
Mikawa
S
S
Kondo
T
T
D000818:Animals; D001921:Brain / Q000378:metabolism*; D001930:Brain Injuries / Q000235:genetics / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism; D018390:Gene Targeting; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
D013482:Superoxide Dismutase