Recovery of postischemic brain metabolism and function following treatment with a free radical scavenger and platelet-activating factor antagonists.
We have studied the metabolic and functional effects of two new platelet-activating factor (PAF) antagonists (BN 50726 and BN 50739) and their diluent (dimethyl sulfoxide; DMSO) during reoxygenation of the 14-min ischemic isolated brain. Blood gases, EEG, auditory evoked potentials, cerebral metabolic rate for glucose (CMRglc), and cerebral metabolic rate for oxygen (CMRO2) were monitored throughout the study. Frozen brain samples were taken for measurement of brain tissue high-energy phosphates, carbohydrate content, and thiobarbituric acid-reactive material (TBAR, an indicator of lipid peroxidation) at the end of the study. Following 60 min of reoxygenation in the nontreated 14-min ischemic brains, lactate, AMP, creatine (Cr), intracellular hydrogen ion concentration [H+]i), and TBAR values were significantly higher and ATP, creatine phosphate (PCr), CMRglc, CMRO2, and energy charge (EC) values were significantly lower than the corresponding normoxic control values. PCr and CMRO2 values were significantly higher, and glycogen, AMP, and [H+]i values were significantly lower in the BN 50726-treated ischemic brains than in DMSO-treated ischemic brains. In brains treated with BN 50739, ATP, ADP, PCr, CMRO2, and EC values were significantly higher, and lactate, AMP, Cr, and [H+]i values were significantly lower than corresponding values in the DMSO-treated ischemic brains. TBAR values were near control levels in all brains exposed to DMSO. There was also marked recovery of EEG and auditory evoked potentials in brains treated with DMSO. Treatment with BN 50726 or BN 50739 in DMSO appeared to improve brain mitochondrial function and energy metabolism partly as the result of DMSO action as a free radical scavenger.(ABSTRACT TRUNCATED AT 250 WORDS)
Gilboe
D D
DD
University of Wisconsin Medical School, Department of Neurosurgery, Madison 53706.
Kintner
D
D
Fitzpatrick
J H
JH
Emoto
S E
SE
Esanu
A
A
Braquet
P G
PG
Bazan
N G
NG
D000249:Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology*; D003401:Creatine / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004285:Dogs; D004569:Electroencephalography; D005072:Evoked Potentials, Auditory; D016166:Free Radical Scavengers; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D007700:Kinetics; D010100:Oxygen / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D058924:Thienopyridines; D014230:Triazoles / Q000494:pharmacology; D014655:Vascular Resistance
D001381:Azepines; D016166:Free Radical Scavengers; D010972:Platelet Activating Factor; D058924:Thienopyridines; D014230:Triazoles; D010725:Phosphocreatine; C061327:BN 50726; C064509:BN 50739; D000249:Adenosine Monophosphate; D006003:Glycogen; D005947:Glucose; D003401:Creatine; D010100:Oxygen; D004121:Dimethyl Sulfoxide