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Recovery of Postischemic Brain Metabolism and Function Following Treatment with a Free Radical Scavenger and Platelet‐Activating Factor Antagonists
Author(s) -
Gilboe D. D.,
Kintner D.,
Fitzpatric J. H.,
Emoto S. E.,
Esanu A.,
Braquet P. G.,
Bazan N. G.
Publication year - 1991
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1991.tb02597.x
Subject(s) - creatine , phosphocreatine , thiobarbituric acid , chemistry , endocrinology , medicine , glycogen , dimethyl sulfoxide , anaerobic exercise , ischemia , free radical scavenger , energy charge , metabolism , biochemistry , lipid peroxidation , energy metabolism , oxidative stress , enzyme , organic chemistry , adenylate kinase , physiology
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 (CMR glc ), and cerebral metabolic rate for oxygen (CMRO 2 ) 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), CMR glc , CMRO 2 , and energy charge (EC) values were significantly lower than the corresponding normoxic control values. PCr and CMRO 2 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, CMRO 2 , 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. The PAF antagonists act at a different level, possibly restoring normal mitochondrial function or preventing some of the adverse effects of increased excitatory amino acid and/or intracellular Ca 2+ levels. This is the only drug combination currently known to promote such complete short‐term metabolic and functional recovery during postischemic reoxygenation.