Cortical Spreading Depression is Associated with Arachidonic Acid Accumulation and Preservation of Energy Charge

The present study aimed to study the relation between the release of arachidonic acid (AA) and the energy state in cerebral cortices of rats during single episodes of cortical spreading depression (CSD). The changes in concentrations of AA, labile phosphate compounds [ATP, ADP, AMP, and phosphocreatine (PCr)], and glycolytic metabolites (lactate, pyruvate, glucose, and glycogen) were studied during and following the large change of the local direct current (DC) potential. Free AA increased markedly during the DC shift, continued to increase during the subsequent 3 min, and returned to control levels at 4–5 min after CSD. PCr decreased by 38% in the first minutes following the DC shift, while ADP increased by 38%. Both returned to normal within a few minutes. ATP, AMP, and energy charge remained constant throughout the experimental period. Glucose decreased by 47% and glycogen by 34% for a few minutes following CSD, while lactate increased by 105% at 2–3 min and by 77% at 4–5 min after CSD. The metabolites returned to control levels at 10 min after CSD. Considering the constant energy charge at all time points during CSD, it is suggested that the AA rise reflects augmented phospholipase activity due to either increased intracellular [Ca2+] or receptor stimulation or both. The possibility that N-methyl-d-aspartate receptors play a role in the release of AA, and that free AA in turn could be part of the mechanism of CSD, is discussed.

[1]  Charles W. Dunnett,et al.  New tables for multiple comparisons with a control. , 1964 .

[2]  J. LaManna,et al.  Effect of ouabain and phenobarbital on oxidative metabolic activity associated with spreading cortical depression in cats , 1975, Brain Research.

[3]  E Sugaya,et al.  Neuronal and glial activity during spreading depression in cerebral cortex of cat. , 1975, Journal of neurophysiology.

[4]  David A. Eberhard,et al.  Intracellular Ca2+ activates phospholipase C , 1988, Trends in Neurosciences.

[5]  M. Lauritzen,et al.  Regional cerebral blood flow during cortical spreading depression in rat brain: increased reactive hyperperfusion in low‐flow states , 1987, Acta neurologica Scandinavica.

[6]  Takao Shimizu,et al.  Arachidonic acid metabolites as intracellular modulators of the G protein-gated cardiac K+ channel , 1989, Nature.

[7]  A. van Harreveld,et al.  Vascular concomitants of spreading cortical depression. , 1952, Journal of neurophysiology.

[8]  A. Hansen,et al.  Extracellular ion concentrations during spreading depression and ischemia in the rat brain cortex. , 1981, Acta physiologica Scandinavica.

[9]  J. Bockaert,et al.  NMDA receptors activate the arachidonic acid cascade system in striatal neurons , 1988, Nature.

[10]  I. Silver,et al.  ATP and Brain Function , 1989, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[11]  A. Gjedde,et al.  Blood‐Brain Glucose Transfer in Spreading Depression , 1981, Journal of neurochemistry.

[12]  L. Sokoloff,et al.  Cerebral glucose utilization: local changes during and after recovery from spreading cortical depression. , 1979, Science.

[13]  L. Wolfe.  Eicosanoids: Prostaglandins, Thromboxanes, Leukotrienes, and Other Derivatives of Carbon‐20 Unsaturated Fatty Acids , 1982, Journal of neurochemistry.

[14]  B. Siesjö,et al.  THE EFFECT OF HYPERCAPNIC ACIDOSIS UPON SOME GLYCOLYTIC AND KREBS CYCLE‐ASSOCIATED INTERMEDIATES IN THE RAT BRAIN , 1972, Journal of neurochemistry.

[15]  A. van Harreveld,et al.  Glutamate release from the retina during spreading depression. , 1970, Journal of neurobiology.

[16]  B. Siesjö,et al.  Influence of Severe Hypoglycemia on Brain Extracellular Calcium and Potassium Activities, Energy, and Phospholipid Metabolism , 1984, Journal of neurochemistry.

[17]  N. Bazan,et al.  Effects of ischemia and electroconvulsive shock on free fatty acid pool in the brain. , 1970, Biochimica et biophysica acta.

[18]  D. R. Curtis,et al.  Analogues of glutamic and gamma-amino-n-butyric acids having potent actions on mammalian neurones. , 1961, Nature.

[19]  F. Dudek,et al.  Electrophysiological and optical changes in slices of rat hippocampus during spreading depression. , 1983, Journal of neurophysiology.

[20]  I. Módy,et al.  Low extracellular magnesium induces epileptiform activity and spreading depression in rat hippocampal slices. , 1987, Journal of neurophysiology.

[21]  A. Harreveld.  COMPOUNDS IN BRAIN EXTRACTS CAUSING SPREADING DEPRESSION OF CEREBRAL CORTICAL ACTIVITY AND CONTRACTION OF CRUSTACEAN MUSCLE , 1959 .

[22]  A. van Harreveld.  Compounds in brain extracts causing spreading depression of cerebral cortical activity and contraction of crustacean muscle. , 1959, Journal of neurochemistry.

[23]  G. Somjen,et al.  Spreading depression, sustained potential shifts, and metabolic activity of cerebral cortex of cats. , 1973, Journal of neurophysiology.

[24]  P. Chan,et al.  Reductions of Γ‐Aminobutyric Acid and Glutamate Uptake and (Na++ K+)‐ATPase Activity in Brain Slices and Synaptosomes by Arachidonic Acid , 1983, Journal of neurochemistry.

[25]  G. Arvidson,et al.  Initial incorporation into rat liver glycerolipids of intraportally injected (3H)glycerol. , 1970, Biochimica et biophysica acta.

[26]  W. Paschen,et al.  Regional changes of blood flow, glucose, and ATP content determined on brain sections during a single passage of spreading depression in rat brain cortex , 1984, Experimental Neurology.

[27]  A. van Harreveld,et al.  The nature of the chick's magnesium-sensitive retinal spreading depression. , 1984, Journal of neurobiology.

[28]  N. Gorelova,et al.  Ketamine blockade of cortical spreading depression in rats. , 1987, Electroencephalography and clinical neurophysiology.

[29]  W. H. Marshall,et al.  Spreading cortical depression of Leao. , 1959, Physiological reviews.

[30]  D. R. Curtis,et al.  Analogues of Glutamic and γ-Amino-n-butyric acids having Potent Actions on Mammalian Neurones , 1961, Nature.

[31]  S. Butcher,et al.  Extracellular Overflow of Neuroactive Amino Acids During Severe Insulin‐Induced Hypoglycemia: In Vivo Dialysis of the Rat Hippocampus , 1986, Journal of neurochemistry.

[32]  A. Mayevsky.  Brain energy metabolism of the conscious rat exposed to various physiological and pathological situations , 1976, Brain Research.

[33]  Louis Sokoloff,et al.  Activity‐dependent Energy Metabolism in Rat Posterior Pituitary Primarily Reflects Sodium Pump Activity , 1980, Journal of neurochemistry.

[34]  J. Křivánek.  Concerning the dynamics of the metabolic changes accompanying cortical spreading depression. , 1962, Physiologia Bohemoslovaca.

[35]  H. Benveniste,et al.  Elevation of the Extracellular Concentrations of Glutamate and Aspartate in Rat Hippocampus During Transient Cerebral Ischemia Monitored by Intracerebral Microdialysis , 1984, Journal of neurochemistry.

[36]  D. E. Atkinson.  The energy charge of the adenylate pool as a regulatory parameter. Interaction with feedback modifiers. , 1968, Biochemistry.

[37]  J. LaManna,et al.  EFFECT OF OUABAIN AND PHENOBARBITAL ON THE KINETICS OF CORTICAL METABOLIC TRANSIENTS ASSOCIATED WITH EVOKED POTENTIALS , 1975, Journal of neurochemistry.

[38]  O. Burešová,et al.  The mechanism and applications of Leão's spreading depression of electroencephalographic activity , 1974 .

[39]  J. Křivánek.  SOME METABOLIC CHANGES ACCOMPANYING LEÃO'S SPREADING CORTICAL DEPRESSION IN THE RAT , 1961, Journal of neurochemistry.

[40]  The meaning and significance of Leão's spreading depression. , 1984, Anais da Academia Brasileira de Ciencias.

[41]  B. Siesjö,et al.  THE EFFECT OF MODERATE AND MARKED HYPERCAPNIA UPON THE ENERGY STATE AND UPON THE CYTOPLASMIC NADH/NAD+ RATIO OF THE RAT BRAIN , 1972, Journal of neurochemistry.

[42]  N. Bazan,et al.  Arachidonic acid, stearic acid, and diacylglycerol accumulation correlates with the loss of phosphatidylinositol 4,5‐bisphosphate in cerebrum 2 seconds after electroconvulsive shock: Complete reversion of changes 5 minutes after stimulation , 1987, Journal of neuroscience research.

[43]  A. A. Leão,et al.  SPREADING DEPRESSION OF ACTIVITY IN THE CEREBRAL CORTEX , 1944 .

[44]  Charles Nicholson,et al.  Quisqualate, kainate and NMDA can initiate spreading depression in the turtle cerebellum , 1988, Brain Research.

[45]  R. Michell.  Inositol phospholipids and cell surface receptor function. , 1975, Biochimica et biophysica acta.

[46]  A. Harreveld,et al.  The nature of the chick's magnesium-sensitive retinal spreading depression , 1984 .

[47]  A. Yu,et al.  Induction of Intracellular Superoxide Radical Formation by Arachidonic Acid and by Polyunsaturated Fatty Acids in Primary Astrocytic Cultures , 1988, Journal of neurochemistry.