Phospholipid Degradation and the Early Release of Polyunsaturated Fatty Acids in the Evolution of Brain Edema
Using both in vitro cortical slices and in vivo models, we have studied the roles of phospholipid degradation and the release of polyunsaturated fatty acid in the evolution of brain edema. We have shown that pus, i.e., fragmented polymorphonuclear leukocytes and other inflammatory cells, acts as a potent inducer of cellular swelling in brain slices13. The swelling factors were identified as free fatty acids, especially polyunsaturated fatty acids (PUFA)5,8. Linoleic acid (18:2), linolenic acid (18:3), arachidonic (20:4) and docosahexaenoic acid (22:6) caused a two to three-fold increase in tissue swelling concomitant with the increase of intracellular sodium and decrease of intracellular potassium. The extracellular inulin space was also decreased indicating the presence of cellular (cytotoxic) edema. This model of cellular edema was also associated with changes in cellular metabolism since lactic acid levels were elevated and high energy nucleotides were reduced13,5.
KeywordsPermeability Prostaglandin Meningitis Macromolecule Thrombin
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- 1.Baethmann A, Oettinger W, Rothenfuber W, Kempski O, Unterberg A, Geiger R: Brain edema factors: Current state with particular reference to plasma constituents and glutamate. In: Brain Edema. Cervos-Navarro J, Ferszt R (Eds). Adv Neurol 28 Raven Press, New York 171–195 (1980).Google Scholar
- 2.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 Brain Edema, Cervos-Navarro J, Ferszt R (Eds). Adv Neurol Raven Press, New York 28: 197–205 (1980).Google Scholar
- 4.Caronna JJ, Chan PH, Fishman RA: Protective effects of cortico-steroids on fatty acid-induced cerebral edema. Trans Am Neurol Assoc 105: 200–204 (1980).Google Scholar
- 10.Chan PH, Fishman RA: Alterations of membrane integrity and cellular constituents by arachidonic acid in neuroblastoma and glioma cells. Brain Res (in press).Google Scholar
- 11.Demopoulos HB, Flamm ES, Seligman ML, Mifamauer 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, 63–68 (1979).Google Scholar
- 12.Demopoulos HB, Flamm ES, Pietronigro DD, Seligman ML: The free radical pathology and the microcirculation in the major central nervous system disorders. Acta Physiol Scand Suppl 492: 91–119 (1980).Google Scholar
- 14.Fishman RA, Chan PH: Metabolic basis of brain edema. Adv Neurol 28: 207–215 (1980).Google Scholar
- 15.Fishman RA, Chan PH: Hypothesis: Membrane phospholipid degrada-tion and polyunsaturated fatty acids play a key role in the pathogenesis of brain edema. Ann Neurol 10: 75 (1981).Google Scholar
- 18.Klausner RD, Kleinfeld AM, Hoover RL, Karnovsky MJ: Lipid domains in membranes. Evidence derived from structural perturbations induced by free fatty acids an lifetime heterogeneity analysis. J Biol Chem 225: 1286–1295 (1980).Google Scholar
- 20.Priolea GR, Fishman RA, Chan PH: Induction of brain edema by fatty acids in vivo. Trans Am Neurol Assoc 104: 147–150 (1979).Google Scholar
- 24.Wojtezak L: Effect of long-chain fatty acids and acyl-CoA on mitrochondrial permeability, transport, and energy-coupling processes. J Bioenerg Biomemb 8: 293–311 (1976).Google Scholar
- 26.Yoshida S, Busto R, Ginsberg MD, Abe K, Watson BD, Scheinberg P: Vitamin E decreases compression-induced brain edema. Neurology 32: A 109 (1982).Google Scholar