Brain levels of polyethylene glycol-conjugated superoxide dismutase following fluid percussion brain injury in rats.
Polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) is being explored as an agent to reduce oxygen radical-mediated damage following brain injury. Yet little is known concerning the site of action of IV-administered PEG-SOD or the capacity of this conjugated enzyme to enter the brain. The purpose of this study was to determine the brain content of PEG-SOD in normal and fluid percussion injured rats. The fluid percussion device was attached over the right parietal cortex and a moderate (2.0 atm) intensity injury was produced. PEG-SOD was conjugated with 125I and given (2000 U/kg, 5 microCi/kg) to rats either 30 min before or 30 min after brain injury. Another group received [125I]PEG-SOD but was not injured. Plasma and left and right brain hemispheres were counted for [125I]PEG-SOD. Plasma levels of [125I]PEG-SOD declined similarly in all three groups during the 90-min period after IV administration. Brain [125I]PEG-SOD was low in control animals (0.034 U/g wet wt). In animals given PEG-SOD after injury the brain level was elevated sixfold in both the left and right hemispheres, compared to control. In rats given the drug before injury, [125I]PEG-SOD was 10 times control level in the right hemisphere, which is the side on which the injury device is attached, and 6 times control level in the left hemisphere. We conclude that traumatic brain injury produces an increase in brain PEG-SOD. The exact cellular site of the increased brain PEG-SOD remains to be clarified.
Yoshida
K
K
Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond.
Burton
G F
GF
Young
H
H
Ellis
E F
EF
D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism* / Q000503:physiopathology; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes; D008297:Male; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000493:pharmacokinetics*
D007457:Iodine Radioisotopes; D011092:Polyethylene Glycols; D013482:Superoxide Dismutase