Polyethylene glycol superoxide dismutase and catalase attenuate increased blood-brain barrier permeability after ischemia in piglets

William M. Armstead, Robert Mirro, Olivier P. Thelin, Masaaki Shibata, Samuel L. Zuckerman, Douglas R. Shanklin, David W. Busija, Charles Leffler

Research output: Contribution to journalArticle

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Abstract

Background and Purpose: Transport of urea across the blood-brain barrier is increased during postischemic cerebral re perfusion 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 [ 14 C]urea from blood to brain increased at 2 hours’ reperfusion. This ischemia-induced increase in blood-to-brain transfer of [ 14 C]urea was attenuated by pretreatment with polyethylene glycol superoxide dismutase and polyethylene glycol catalase: e.g., cerebrum Kt. 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 . 106 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.

Original languageEnglish (US)
Pages (from-to)755-762
Number of pages8
JournalStroke
Volume23
Issue number5
DOIs
StatePublished - Jan 1 1992

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Blood-Brain Barrier
Catalase
Permeability
Ischemia
Reperfusion
Urea
Brain
Superoxides
Cerebrum
polyethylene glycol-superoxide dismutase
Cerebrovascular Circulation
Swine
Pons
Mesencephalon
Brain Ischemia
Cerebellum
Carbon
Perfusion
Oxygen
Control Groups

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

Cite this

Polyethylene glycol superoxide dismutase and catalase attenuate increased blood-brain barrier permeability after ischemia in piglets. / Armstead, William M.; Mirro, Robert; Thelin, Olivier P.; Shibata, Masaaki; Zuckerman, Samuel L.; Shanklin, Douglas R.; Busija, David W.; Leffler, Charles.

In: Stroke, Vol. 23, No. 5, 01.01.1992, p. 755-762.

Research output: Contribution to journalArticle

Armstead, WM, Mirro, R, Thelin, OP, Shibata, M, Zuckerman, SL, Shanklin, DR, Busija, DW & Leffler, C 1992, 'Polyethylene glycol superoxide dismutase and catalase attenuate increased blood-brain barrier permeability after ischemia in piglets', Stroke, vol. 23, no. 5, pp. 755-762. https://doi.org/10.1161/01.STR.23.5.755
Armstead, William M. ; Mirro, Robert ; Thelin, Olivier P. ; Shibata, Masaaki ; Zuckerman, Samuel L. ; Shanklin, Douglas R. ; Busija, David W. ; Leffler, Charles. / Polyethylene glycol superoxide dismutase and catalase attenuate increased blood-brain barrier permeability after ischemia in piglets. In: Stroke. 1992 ; Vol. 23, No. 5. pp. 755-762.
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abstract = "Background and Purpose: Transport of urea across the blood-brain barrier is increased during postischemic cerebral re perfusion 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 [ 14 C]urea from blood to brain increased at 2 hours’ reperfusion. This ischemia-induced increase in blood-to-brain transfer of [ 14 C]urea was attenuated by pretreatment with polyethylene glycol superoxide dismutase and polyethylene glycol catalase: e.g., cerebrum Kt. 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 . 106 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.",
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T1 - Polyethylene glycol superoxide dismutase and catalase attenuate increased blood-brain barrier permeability after ischemia in piglets

AU - Armstead, William M.

AU - Mirro, Robert

AU - Thelin, Olivier P.

AU - Shibata, Masaaki

AU - Zuckerman, Samuel L.

AU - Shanklin, Douglas R.

AU - Busija, David W.

AU - Leffler, Charles

PY - 1992/1/1

Y1 - 1992/1/1

N2 - Background and Purpose: Transport of urea across the blood-brain barrier is increased during postischemic cerebral re perfusion 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 [ 14 C]urea from blood to brain increased at 2 hours’ reperfusion. This ischemia-induced increase in blood-to-brain transfer of [ 14 C]urea was attenuated by pretreatment with polyethylene glycol superoxide dismutase and polyethylene glycol catalase: e.g., cerebrum Kt. 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 . 106 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.

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