Polyethylene glycol superoxide dismutase and catalase attenuate increased blood-brain barrier permeability after ischemia in piglets.
OBJECTIVE
Transport of urea across the blood-brain barrier is increased during postischemic cerebral reperfusion in the piglet. Ischemia/reperfusion also has been observed to increase apparent superoxide anion generation on the surface of the brain. The present study was designed to address the hypothesis that the increased transfer of urea into the brain after ischemia/reperfusion could be due to superoxide anion-induced alterations in blood-brain barrier permeability.


METHODS
Blood-to-brain transfer of carbon-14-labeled urea was measured in four groups (n = 7 each) of newborn pigs: 1) control (no ischemia, no pretreatment), 2) pretreatment with polyethylene glycol superoxide dismutase (1,000 IU/kg) and polyethylene glycol catalase (10,000 IU/kg i.v.) but no ischemia, 3) no pretreatment and 20 minutes of ischemia followed by 2 hours of reperfusion, and 4) pretreatment with polyethylene glycol superoxide dismutase and polyethylene glycol catalase in addition to ischemia/reperfusion. The following brain regions were investigated: cerebrum, caudate, midbrain, pons, medulla, and cerebellum.


RESULTS
Polyethylene glycol superoxide dismutase inhibited generation of superoxide anion by the brain during reperfusion after ischemia. Regional transfer of [14C]urea from blood to brain increased at 2 hours' reperfusion. This ischemia-induced increase in blood-to-brain transfer of [14C]urea was attenuated by pretreatment with polyethylene glycol superoxide dismutase and polyethylene glycol catalase: e.g., cerebrum Kin was 28 +/- 2 in the control group, 26 +/- 3 in the pretreated/no ischemia group, 67 +/- 5 in the untreated/ischemia group, and 40 +/- 2 ml.g-1.s-1.10(6) in the pretreated/ischemia group. After ischemia/reperfusion, cerebral blood flow was unchanged by pretreatment with polyethylene glycol superoxide dismutase and polyethylene glycol catalase.


CONCLUSIONS
These data suggest that production of a partially reduced species of oxygen contributes to the increased urea transfer across the blood-brain barrier after ischemia in the newborn pig.
Armstead
W M
WM
Department of Physiology, University of Tennessee, Memphis 38163.
Mirro
R
R
Thelin
O P
OP
Shibata
M
M
Zuckerman
S L
SL
Shanklin
D R
DR
Busija
D W
DW
Leffler
C W
CW
D000818:Animals; D000831:Animals, Newborn; D001808:Blood Vessels / Q000648:ultrastructure; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology*; D002199:Capillary Permeability / Q000187:drug effects*; D002374:Catalase / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D016166:Free Radical Scavengers; D008833:Microcirculation; D009580:Nitroblue Tetrazolium; D011092:Polyethylene Glycols / Q000494:pharmacology*; D015424:Reperfusion; D013482:Superoxide Dismutase / Q000494:pharmacology*; D013552:Swine; D014508:Urea / Q000493:pharmacokinetics
D016166:Free Radical Scavengers; C070295:catalase-polyethylene glycol; D009580:Nitroblue Tetrazolium; D011092:Polyethylene Glycols; D014508:Urea; D002374:Catalase; D013482:Superoxide Dismutase; C063471:polyethylene glycol-superoxide dismutase