Effects of alpha-phenyl-N-tert-butyl nitrone (PBN)on brain cell membrane function and energy metabolism during transient global cerebral hypoxia-ischemia and reoxygenation-reperfusion in newborn piglets.
We sought to know whether a free radical spin trap agent, alpha-phenyl-N-tert-butyl nitrone (PBN) influences brain cell membrane function and energy metabolism during and after transient global hypoxia-ischemia (HI) in the newborn piglets. Cerebral HI was induced by temporary complete occlusion of bilateral common carotid arteries and simultaneous breathing with 8% oxygen for 30 min, followed by release of carotid occlusion and normoxic ventilation for 1 hr (reoxygenation-reperfusion,RR). PBN (100 mg/kg) or vehicle was administered intravenously just before the induction of HI or RR. Brain cortex was harvested for the biochemical analyses at the end of HI or RR. The level of conjugated dienes significantly increased and the activity of Na+, K+ -ATPase significantly decreased during HI,and they did not recover during RR. The levels of ATP and phosphocreatine (PCr)significantly decreased during HI, and recovered during RR. PBN significantly decreased the level of conjugated dienes both during HI and RR, but did not influence the activity of Na+, K+ -ATPase and the levels of ATP and PCr. We demonstrated that PBN effectively reduced brain cell membrane lipid peroxidation, but did not reverse ongoing brain cell membrane dysfunction nor did restore brain cellular energy depletion, in our piglet model of global hypoxic-ischemic brain injury.
Choi
Chang Won
CW
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Hwang
Jong Hee
JH
Chang
Yun Sil
YS
Shin
Son Moon
SM
Park
Won Soon
WS
Lee
Munhyang
M
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002462:Cell Membrane / Q000378:metabolism*; D002540:Cerebral Cortex; D003497:Cyclic N-Oxides; D000860:Hypoxia; D007511:Ischemia; D015227:Lipid Peroxidation; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009589:Nitrogen Oxides / Q000494:pharmacology*; D010725:Phosphocreatine / Q000031:analogs & derivatives* / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013552:Swine; D013997:Time Factors
D003497:Cyclic N-Oxides; D018696:Neuroprotective Agents; D009589:Nitrogen Oxides; D010725:Phosphocreatine; C029217:phenyl-N-tert-butylnitrone; C025403:phosphocreatinine; D000255:Adenosine Triphosphate; D000254:Sodium-Potassium-Exchanging ATPase