Endogenous Pools of Arachidonic Acid-Enriched Membrane Lipids in Cryogenic Brain Edema

  • Nicolas G. Bazan
  • Enrique Politi
  • Elena B. de Rodriguez Turco


The understanding of neurochemical changes associated with the evolution of brain edema is a prerequisite to the development of newer and more effective treatments of this condition. During brain edema, phospholipids and their long-chain highly unsaturated acyl groups, especially arachidonic and docosahexaenoic acids, have been postulated to be the earliest membrane components altered17. This is based on the finding that there is an increase in free fatty acid pool size at the onset of ischemia7,10,13,15,21,30,36,37,39,44, carotid artery ligation , and hypoxia . This lipid effect has been seen in several animals, including primates’. Arachidonic, stearic, docosahexaenoic, palmitic, and oleic acids are produced rapidly at the onset of ischemia”. Using head-focus microwave irradiation, it has been shown that rapid brain fixation reduces the free fatty acid pool size to trace levels and that accumulation of these free fatty acids already can be measured during the first few seconds of oxygen deprivation21.


Free Fatty Acid Brain Edema Cerebral Hemisphere Free Fatty Acid Level Electroconvulsive Shock 
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  1. 1.
    Aveldano MI, Bazan NG: Displacement into incubation medium by albumin of highly unsaturated retina free fatty acids arising from membrane lipids. FEBS Lett. 40: 53–56 (1974).CrossRefGoogle Scholar
  2. 2.
    Aveldano MI, Bazan NG: Rapid production of diacylglycerols enriched in arachidonate and stearate during early brain ischemia. J Neurochem 25: 919–920 (1975).CrossRefGoogle Scholar
  3. 3.
    Aveldano MI, Bazan NG:-methyl-p-tyrosine inhibits the production of free arachidonic acid and diacylglycerols in brain after a single electroconvulsive shock. Neurochem Res 4: 213–221 (1979).CrossRefGoogle Scholar
  4. 4.
    Aveldano MI, Giusto NM, Bazan NG: Polyunsaturated fatty acids of the retina. Prog Lipid Res 20: 49–57 (1982).Google Scholar
  5. 5.
    Banschbach MW, Geison RL: Post-mortem increase in rat cerebral hemisphere diglyceride pool size. J Neurochem 23: 875–877 (1974).CrossRefGoogle Scholar
  6. 6.
    Bazan NG: Effects of ischemia and electroconvulsive shock on free fatty acid pool in the brain. Biochim Biophys Acta 218: 1–10 (1970).CrossRefGoogle Scholar
  7. 7.
    Bazan NG: Free fatty acid production in cerebral white and grey matter of the squirrel monkey. Lipids 6: 211–212 (1971).CrossRefGoogle Scholar
  8. 8.
    Bazan NG: Changes in free fatty acids of the brain by drug-induced convulsions, electroshock and anesthesia. J Neurochem 18: 1379–1385 (1971).CrossRefGoogle Scholar
  9. 9.
    Bazan NG: Modification in the free fatty acids of developing rat brain. Acta Physiol Lat Am 21: 15–20 (1971).Google Scholar
  10. 10.
    Bazan NG: Free arachidonic acid and other lipids in the nervous system during early ischemia and after electroshock. Adv Exp Med Biol 72: 317–335 (1976).CrossRefGoogle Scholar
  11. 11.
    Bazan NG: Free arachidonic acid and arachidonoyl-diglycerides in brain edema and in epileptic seizures. Eighth Meeting of the International Society for Neurochemistry, Nottingham, England. 235 (1981).Google Scholar
  12. 12.
    Bazan NG, Aveldano de Caldironi MI, Rodriguez de Turco EB: Rapid release of free arachidonic acid in the central nervous system due to stimulation. Prog Lipid Res 20: 523–529 (1982).CrossRefGoogle Scholar
  13. 13.
    Bazan NG, Aveldano MI, Rodriguez de Turco EB: Rapid release of free arachidonic acid in the central nervous system due to stimulation. Progr Lip Res 20: 523–529 (1982).CrossRefGoogle Scholar
  14. 14.
    Bazan NG, Bazan HEP: Analysis of free and sterified fatty acids in neural tissue using gradient-thickness thin-layer chroma-tography, In: Res Methods in Neurochem, 3 (Marks N, Rodnight R, Eds.) Plenum Press, New York 309–324 (1975).CrossRefGoogle Scholar
  15. 15.
    Bazan NG, Bazan HEP, Kennedy WG, Joel CD: Regional distribution and rate of production of free fatty acids in rat brain. J Neurochem 18: 1387–1393 (1971).CrossRefGoogle Scholar
  16. 16.
    Bazan NG, Joel CD: Gradient-thickness thin-layer chromatography for the isolation and analysis of trace amounts of free fatty acids in large lipid samples. J Lipid Res 11: 42–47 (1970).Google Scholar
  17. 17.
    Bazan NG, Rodriguez de Turco EB: Membrane lipids in the patho-genesis of brain edema: phospholipids and arachidonic acid, the earliest membrane components changed at the onset of ischemia, in Adv Neurol, 28 Brain Edema, (Cervos Navarro J, Ferszt R, Eds.) Raven Press, New York 197–205 (1980).Google Scholar
  18. 18.
    Bazan NG, Rakowski H: Increased levels of brain free fatty acids after electroconvulsive shock. Life Sci 9: 501–507 (1970).CrossRefGoogle Scholar
  19. 19.
    Bosisio E, Galli C, Galli G, Nicosia S, Spagnuolo C, Tosi L: Correlation between release of free arachidonic acid and prostaglandin formation in brain cortex and cerebellum. Prostaglandins 11: 773–782 (1976).Google Scholar
  20. 20.
    Bourre J, Gozlan-Devillierre N, Pollet S, Maurin Y, Baumann N: In vivo incorporation of exogenous stearic acid in synapto-somes: high occurrence of non-esterified fatty acids. Neurosci Lett 4: 309–313 (1977).CrossRefGoogle Scholar
  21. 21.
    Cendella RJ, Galli C, Paoletti R: Brain free fatty acid levels in rats sacrificed by decapitation versus focused microwave irradiation. Lipids 10: 290–293 (1975).CrossRefGoogle Scholar
  22. 22.
    Chan PH, Fishman RA: Brain edema: induction in cortical slices by polyunsaturated fatty acids. Science 201: 358–360 (1978).CrossRefGoogle Scholar
  23. 23.
    Chan PH, Fishman RA: Transient formation of Superoxide radicals in polyunsaturated fatty acid-induced brain swelling. J Neuro-chem 35: 1004–1007 (1980).Google Scholar
  24. 24.
    Chan PH, Quan SC, Fishman RA: Inhibition of rat brain (Na++ K+)-ATPase by polyunsaturated fatty acids. Trans Am Soc Neuro-chem 11: 120 (1980).Google Scholar
  25. 25.
    Crockard HA, Bhakoo KK, Lascelles PT: Regional prostaglandin levels in cerebral ischaemia. J Neurochem 38: 1311–1314 (1982).CrossRefGoogle Scholar
  26. 26.
    Demopoulos HB, Flamm ES, Seligman ML, Mitamauir JA, Ransohoff J: Membrane perturbations in central nervous system injury: Theoretical basis for free radical damage and a review of the experimental data. In: Neural Trauma (Popp J, Bourke RS, Nelson LR, Kimelberg HK, Eds.) Raven Press, New York 63–78 (1979).Google Scholar
  27. 27.
    Der OM, Sun GY: Degradation of arachidonoyl-labeled phosphati-dylinositols by brain synaptosomes. J Neurochem 36: 355–362 (1981).CrossRefGoogle Scholar
  28. 28.
    Folch J, Lees M, Sloane-Stanley GH: A simple method for the isolation and purification of total lipids from animal tissue. J Biol Chem 226: 497–509 (1957).Google Scholar
  29. 29.
    Fritschka E, Ferguson JL, Spitzer JJ: Increased free fatty acid turnover in CSF during hypotension in dogs. Am J Physiol 236: H802–H807 (1979).Google Scholar
  30. 30.
    Galli C, Spagnuolo C: The release of brain free fatty acids during ischemia in essential fatty acid-deficient rats. J Neurochem 26: 401–404 (1976).CrossRefGoogle Scholar
  31. 31.
    Galli C, Spagnuolo C, Bosiso E, Tosi L, Folco GC, Galli G: Dietary essential fatty acids, polyunsaturated fatty acids, and prostaglandins in the central nervous system. In: Advances in Prostaglandin and Thromboxane Research 4 (Coceani F, Olley PM, Eds.) Raven Press, New York 181–189 (1978).Google Scholar
  32. 32.
    Galli C, Spagnuolo C, Petroni A: Factors affecting brain prostaglandin formation, in Advances in Prostaglandin and Thromboxane Research 8 (Samuelsson B, Ramwell PW, Paoletti R, Eds.) Raven Press, New York: 1235–1239 (1980).Google Scholar
  33. 33.
    Gardiner M, Nilsson B, Rehncrona S, Siesjo BK: Free fatty acids in the rat brain in moderate and severe hypoxia. J Neurochem 36: 1500–1505 (1981).CrossRefGoogle Scholar
  34. 34.
    Gaudet RJ, Levine L: Transient cerebral ischemia and brain prostaglandins. Biochem Biophys Res Comm 86: 893–901 (1979).CrossRefGoogle Scholar
  35. 35.
    Klatzo I, Wisniewski H, Steinwall O, Streicher E: Dynamics of cold injury edema, in Brain Edema (Klatzo I, Seitelberger F, Eds.) Springer-Verlag, New York 554–563 (1967).CrossRefGoogle Scholar
  36. 36.
    Kuwashima J, Nakamura K, Fujitani B, Kadokawa T, Yoshida K, Shimizu M: Relationship between cerebral energy failure and free fatty acid accumulation following prolonged brain ischemia. Jpn J Pharmacol 28: 277–287 (1978).CrossRefGoogle Scholar
  37. 37.
    Lazarewicz JW, Strosznajder J, Grome KA: Effect of ischemia and exogenous fatty acids on the energy metabolism in brain mitochondria. Bui Acad Pol Sci (Biol) 20: 599–606 (1972).Google Scholar
  38. 38.
    Marion J, Wolfe LS: Increase in vivo of unesterified fatty acids, prostaglandin F but not thromboxane B2 in rat brain during drug induced convulsions. Prostaglandins 16: 99–110 (1978).Google Scholar
  39. 39.
    Marion J, Wolfe LS: Origin of the arachidonic acid released post-mortex in rat forebrain. Biochim Biophys Acta 574: 25–32 (1979).CrossRefGoogle Scholar
  40. 40.
    Ogburn PL, Sharp H, Lloyd-Still JD, Johnson SB, Holman RT: Abnormal polyunsaturated fatty acid patterns of serum lipids in Reye’s syndrome. Proc Natl Acad Sci USA 79: 908–911 (1982).CrossRefGoogle Scholar
  41. 41.
    Pickard JD: Role of prostaglandins and arachidonic acid derivatives in the coupling of cerebral blood flow to cerebral metabolism. J Cerebral Blood Flow Metabol 1: 361–384 (1981).CrossRefGoogle Scholar
  42. 42.
    Porcellati G, DeMedio GE, Fini C, Floridi A, Goracci G, Horrocks LA, Lazarewicz JW, Palmerini CA, Strosznajder J, Trovarelli G: Phospholipid and its metabolism in ischemia. Proc Eur Soc Neurochem 1: 285–302 (1978).Google Scholar
  43. 43.
    Rehncrona S, Smith DS, Akesson B, Westerberg E, Siesjö BK: Peroxidative changes in brain cortical fatty acids and phospho-lipids, as characterized during Fe2+ and ascorbic acid-stimulated lipid peroxidation “in vitro”. J Neurochem 34: 1630–1638 (1980).CrossRefGoogle Scholar
  44. 44.
    Rehncrona S, Westerberg E, Akesson B, Siesjö BK: Brain cortical fatty acids and phospholipids during and following complete and severe incomplete ischemia. J Neurochem 38: 84–93 (1982).CrossRefGoogle Scholar
  45. 45.
    Rhoads DE, Kaplan MA, Peterson NA, Raghupathy E: Effects of free fatty acids on synaptosomal amino acid uptake systems. J Neurochem 38: 1255–1260 (1982).CrossRefGoogle Scholar
  46. 46.
    Rodriguez de Turco EB, Cascone GD, Pediconi MF, Bazan NG: Phosphatidate, phosphatidylinositol, diacylglycerols and free fatty acids in the brain following electroshock, anoxia or ischemia. Adv Exp Med Biol 72: 389–396 (1977).CrossRefGoogle Scholar
  47. 47.
    Rodriguez de Turco EB, Morrelli SA, Bazan NG: Stimulation and free fatty acid and diacylglycerol accumulation in cerebrum and cerebellum during bicuculline-induced status epilepticus. Effect of pretreatment with a ×-methyl-p-tyrosine and p-chlorophenyllalanine. J Neurochem. (In Press) (1982).Google Scholar
  48. 48.
    Siesjö BK: Cell damage in the brain: a speculative synthesis. J Cerebral Blood Flow Metabol 1: 155–185 (1981).CrossRefGoogle Scholar
  49. 49.
    Spagnuolo C, Petroni A, Blasevich M, Galli C: Differential effects of probenecid on the levels of endogenous PGF2× and TXB2 in brain cortex. Prostaglandins 18, 311–315 (1979).Google Scholar
  50. 50.
    Spagnuolo C, Sautebin L, Galli G, Racagni G, Galli C, Mazzari S, Finesso M: PGF2× thromboxane B2 and HETE levels in gerbilbrain cortex after ligation of common carotid arteries and decapitation. Prostaglandins 18: 53–61 (1979).Google Scholar
  51. 51.
    Spagnuolo C, Terzi C, Galli C: Differential response of brain PGF synthesis to methionine sulfoximine in respect of other convulsant drugs. Pharm Res Comm 10: 541–544 (1978).CrossRefGoogle Scholar
  52. 52.
    Spitzer JJ: Application of tracers in studying free fatty acid metabolism of various organs in vivo. Fed Proc 34: 2242–2245 (1975).Google Scholar
  53. 53.
    Steinhauer HB, Anhut H, Hertting G: The synthesis of prostaglandins and thromboxane in the mouse brain in vivo. Influence of drug induced convulsion, hypoxia and the anticonvulsants trimethadione and diazepam. Naunyn-Schmiedeberg’s Arch Pharmacol 310: 53–58 (1979).CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • Nicolas G. Bazan
    • 1
  • Enrique Politi
    • 2
  • Elena B. de Rodriguez Turco
    • 2
  1. 1.LSU Eye Center, Louisiana State University Medical CenterSchool of MedicineNew OrleansUSA
  2. 2.Instituto de Investigaciones BioquimicasUniversidad Nacional de Sur-Consejo Nacional de Investigaciones Cientificas y TecnicasBahia BiancaArgentina

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