The generation of oxygen radicals and the process of lipid peroxidation have become a focus of attention for investigators in the fields of central nervous system (CNS) injury and stroke (e.g., ischemia). While absolute proof for their involvement in the pathophysiology of traumatic and ischemic damage to the CNS remains to be established, numerous recent studies have provided considerable support for the occurrence of free radical and lipid peroxidation reactions in the injured or ischemic CNS. Furthermore, the use of antioxidants and free radical scavengers in the treatment of experimental and clinical CNS trauma and ischemia has provided convincing support for the involvement of oxygen radicals and lipid peroxidation in these conditions. In this report we will review some of the history behind the hypothesis for an involvement of oxygen radical-mediated lipid peroxidation in the pathophysiology of CNS injury and look at some of the more recent work conducted in this area.
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References
1.
ANDERSOND.K., and MEANSE.D. (1983). Lipid peroxidation in spinal cord: FeCl2 induction and protection with antioxidants. Neurochem. Pathol.1, 249–264.
2.
ANDERSOND.K., SAUNDERSR.D., DEMEDIUKP., and HORROCKSL.E. (1985). Lipid hydrolysis and peroxidation in injured spinal cord: partial protection with methylprenisolone or vitamin E and selenium. Cent. Nerv. Syst. Trauma2, 257–267.
3.
BRACKENM.B., SHEPARDJ.J., COLLINSW.F., et al. (1990). A randomized controlled trial of methylprednisolone or naloxone in the treatment of acute spinal cord injury. N. Engl. J. Med.322, 1405–1411.
4.
BRAUGHLERJ.M. (1985). Lipid peroxidation-induced inhibition of gamma-aminobutyric acid uptake in rat brain synaptosomes: Protection by glucocorticoids. J. Neurochem.44, 1282–1288.
5.
BRAUGHLERJ.M., and HALLE.D. (1989). Central nervous system trauma and stroke: I. Biochemical considerations for oxygen radical formation and lipid peroxidation. Free Radical Biol. Med.6, 289–301.
6.
BRAUGHLERJ.M., and HALLE.D. (1982). Correlation of methylprednisolone levels in cat spinal cord with its effects on (Na+ + K+)-ATPase, lipid peroxidation, and alpha motor neuron function. J. Neurosurg.56, 838–844.
7.
BRAUGHLERJ.M., and HALLE.D. (1985). Current application of "high-dose" steroid therapy for CNS injury: A pharmacological perspective. J. Neurosurg.62, 806–810.
8.
BRAUGHLERJ.M., and HALLE.D. (1984). Effects of multi-dose methylprednisolone sodium succinate administration on injured cat spinal cord neurofilament degradation and energy metabolism. J. Neurosurg.61, 290–295.
9.
BRAUGHLERJ.M., and HALLE.D. (1983a). Lactate and pyruvate metabolism in injured cat spinal cord before and after a single large intravenous dose of methylprednisolone. J. Neurosurg.59, 256–261.
10.
BRAUGHLERJ.M., and HALLE.D. (1983b). Uptake and elimination of methylprednisolone from contused cat spinal cord following intravenous injection of the sodium succinate ester. J. Neurosurg.58, 538–542.
11.
BRAUGHLERJ.M., HALLE.D., MEANSE.D., and ANDERSOND.K. (1987). Evaluation of an intensive CNS injury dosing regimen of methylprednisolone sodium succinate in experimental spinal cord injury. J. Neurosurg.67, 102–105.
12.
CAOW., CARNEYJ.M., DUCHONA., FLOYDR.A., and CHEVIONM. (1988). Oxygen free radical involvement in ischemia and reperfusion injury to brain. Neurosci. Letts.88, 233–238.
13.
CHANP.H., SCHMIDLEYJ.W., FISHMANR.A., and LANGARS.M. (1984). Brain injury, edema, and vascular permeability changes induced by oxygen-derived free radicals. Neurology34, 315–320.
14.
DEMOPOULOSH.B., GLAMME.S., PIETRONIGROD.D., and SELIGMANM.L. (1980). The free radical pathology and the microcirculation in the major central nervous system disorders. Acta Physiol. Scand.[Suppl.] 492, 91–119.
15.
DEMOPOULOSH.B., MILVYP., KAKARIS., and RANSOHOFFJ. (1972). Molecular aspects of membrane structure in cerebral edema, in Steroids and Brain Edema. ReulenH.J. and SchurmannK. (eds). Springer Verlag: New York, pp. 29–39.
16.
DZHAFAROVA.I., MAGOMEDROVN.M., KULIEVAE.M., et al. (1985). Lipid peroxidation in outer and inner mitochondrial membranes during anoxia. Byull. Eksper. Biol. Med. (USSR)100, 433–435.
17.
FOLBERGROVAJ., NILSSONB., SAKABET., SIESJOB.K. (1981). Influence of hypoxia on the concentrations of cyclic nucleotides in the rat brain. J. Neurochem.36, 1670–1674.
18.
FRANCESCOV., CESAREA., LUIGII., STEFANOF., ANDREAG., and FRANCESCOB. (1985). Malondialdehyde-like material and beta-thromboglobulin plasma levels in patients suffering from transient ischemic attacks. Stroke16, 14–16.
19.
FUJIMOTOS., MIZOIK., YOSHIMOTOT., and SUZUKIJ. (1984). The protective effect of vitamin E on cerebral ischemia. Surg. Neurol.22, 449–454.
20.
GRAFFG., STEPHENSONJ.H., GLASSD.B., HADDOXM.K., and GOLDBERGN.D. (1978). Activation of soluble splenic cell guanylate cyclase by prostaglandin endoperoxides and fatty acid hydroperoxides. J. Biol. Chem.253, 7662–7676.
21.
GUTTERIDGEJ.M.C. (1986). Aspects to consider when detecting and measuring lipid peroxidation. Free Radical Res. Commun.1, 173–184.
22.
HALLE.D. (1985). High-dose glucocorticoid treatment improves neurological recovery in head-injured mice. J. Neurosurg.62, 882–887.
23.
HALLE.D., and BRAUGHLERJ.M. (1981). Acute effects of intravenous glucocorticoid pretreatment on the in vitro peroxidation of cat spinal cord tissue. Exp. Neurol.73, 321–324.
24.
HALLE.D., and BRAUGHLERJ.M. (1989). Central nervous system trauma and stroke: II. Physiological and pharmacological evidence for the involvement of oxygen radicals and lipid peroxidation. Free Radical Biol. Med.6, 303–313.
25.
HALLE.D., and BRAUGHLERJ.M. (1982a). Effects of intravenous methylprednisolone on spinal cord lipid peroxidation and (Na+ + K+) ATPase activity. J. Neurosurg.57, 247–253.
26.
HALLE.D., and BRAUGHLERJ.M. (1982b). Glucocorticoid mechanisms in spinal cord injury: A review and therapeutic rationale. Surg. Neurol.18, 320–327.
27.
HALLE.D., PAZARAK.E., and BRAUGHLERJ.M. (1989b). Effects of the 21-aminosteroid, U-74006, on post ischemic depletion of Vitamin E and recovery of extracellular calcium. J. Cereb. Blood Flow Metab.19, S561.
28.
HALLE.D., PARAZAK.E., and LINSEMANK.L. (1991). Sex difference in post-ischemic neuronal necrosis in gerbils. J. Cereb. Blood Flow Metab.11, 292–298.
29.
HALLE.D., WOLFD.L., and BRAUGHLERJ.M. (1984). Effects of a single large dose of methylprednisolone sodium succinate on post-traumatic spinal cord ischemia: Dose-response and time-action analysis. J. Neurosurg.61, 124–130.
30.
HALLE.D., YONKERSP.A., HORANK.L., and BRAUGHLERJ.M. (1989a). Correlation between attenuation of post-traumatic spinal cord ischemia and preservation of tissue vitamin E by the 21-aminosteroid U-74006F: Evidence for an in vivo antioxidant mechanism. J. Neurotrauma6, 169–176.
31.
HORNINGE.C., and LINS.N. (1978). Analytical studies of human plasma lecithins, cholesteryl esters, free fatty acids and α-tocopherol, in: Tocopherol, Oxygen and Biomembranes. deDuveC. and HayaishiO. (eds). Elsevier Biomedical Press: New York, pp. 273–282.
32.
IMAIZUMIS., KAYAMAT., and SUZUKIJ. (1984). Chemiluminescence in hypoxic brain the first report: Correlation between energy metabolism and free radical reaction. Stroke15, 1061–1065.
33.
KONATG.W., and WIGGINSR.C. (1985). Effect of reactive oxygen species on myelin membrane proteins. J. Neurochem.45, 1113–1118.
34.
KRAMERK., RADEMAKERB., ROSENDALW.H.M., TIMMERMANH., and BASTA. (1986). Influence of lipid peroxidation of beta-adrenoceptors. FEBS Letts.198, 80–84.
35.
KURIHARAM. (1985). Role of monamines in experimental spinal cord injury: Relationship between Na+ + K+ ATPase and lipid peroxidation. J. Neurosurg.62, 743–749.
36.
MCGINLEYP., BRAUGHLERJ.M., and HALLE.D. (1982). Determination of methylprednisolone in central nervous tissue and plasma using normal phase high performance liquid chromatography. J. Chromatogr.230, 29–35.
37.
MEANSE.D., ANDERSOND.K., WATERST.R., and KALAFF. (1981). Effects of methylprednisolone in compression trauma to the feline spinal cord. J. Neurosurg.55, 100–208.
38.
MIKELH.S., VAISHNAVY.N., KEMPSKIO., VON LUBITZD., WEISSJ.F., and FEUERSTEING. (1987). Breathing 100% oxygen after global brain ischemia in mongolian gerbils results in increased lipid peroxidation and increased mortality. Stroke18, 426–430.
39.
MURADF., ARNOLDW.P., MITTALC-K., and BRAUGHLERJ.M. (1979). Properties and regulation of guanylate cyclase and some propfunctions for cyclic GMP, in: Advances in Cyclic Nucleotide Research. GreengardP. and RobisonG.A. (eds). Raven Press: New York, pp. 175–204.
40.
NATALEJ.E., SCHOTTR.J., HALLE.D., BRAUGHLERJ.M., and D'ALECYL.G. (1988). The 21-aminosteroid U74006F reduces systemic lipid peroxidation, improves neurological function, and reduces mortality after cardiopulmonary arrest in dogs. Stroke19, 1371–1378.
41.
OLIVERC.N., STARKE-REEDP.E., STADTMANE., CARNEYJ.M., LIUG., and FLOYDR.A. (1990). Ischemia/reperfusion induced free radical formation as assessed by spin trapping and oxidative damage to proteins in gerbil brain. FASEB4, 5520.
42.
PASCOEG.A., and REEDD.J. (1989). Cell calcium, vitamin E, and the thiol redox system in cytotoxicity. Free Radical Biol. Med.6, 209–224.
43.
PIETRONIGROD.D., HOVSEPIANM., DEMOPOULOSH.B., and FLAMME.S. (1983). Loss of ascorbic acid from injured feline spinal cord. J. Neurochem.41, 1072–1076.
44.
REHNCRONAS., FOLBERGROVAJ., SMITHD.S., and SIESJOB.K. (1980). Influence of complete and pronounced incomplete cerebral ischemia and subsequent recirculation on cortical concentrations of oxidized and reduced glutathione in the rat. J. Neurochem.34, 477–486.
45.
SAUNDERSR.D., DUGANL.L., DEMIDIUKP., MEANSE.D., HORROCKSL.A., and ANDERSOND.K. (1987). Effects of methylprednisolone and the combination of α-tocopherol and selenium on arachidonic acid metabolism and lipid peroxidation in traumatized spinal cord tissue. J. Neurochem.49, 24–31.
46.
SELIGMANM.L., MITAMURAJ., SHERAN., and DEMOPOULOSH.B. (1979). Corticosteroid (methylprednisolone) modulation of photoperoxidation by ultraviolet light in liposomes. Photochem. Photobiol.29, 549–558.
47.
SUZUKIJ., IMAIZUMIS., KAYAMAT., and YOSHIMOTOT. (1985). Chemiluminescence in hypoxic brain the second report: Cerebral protective effect of mannitol, vitamin E and glucocorticoid. Stroke16, 695–700.
TRAVISM.A., and HALLE.D. (1987). The effects of chronic two-fold dietary vitamin E supplementation on subarachnoid hemorrhage-induced brain hypoperfusion. Brain Res.418, 366–370.
50.
WATSONB.D., BUSTR., GOLDBERGW.J., SANTISOM., YOSHIDAS., and GINSBERGM.D. (1984). Lipid peroxidation in vivo induced by reversible global ischemia in rat brain. J. Neurochem.42, 268–274.
51.
WILLMOREL.J., and RUBINJ.J. (1982). Formation of malondialdehyde and focal brain edema induced by subspinal injection of FeCl2 into rat isocortex. Brain Res.246, 113–119.
52.
YOSHIDAS., ABEK., BUSTR., WATSONB.D., KOGUREK., and GINSBERGM.D. (1982). Influence of transient ischemia on lipid soluble antioxidants, free fatty acids and energy metabolites in rat brain. Brain Res.245, 307–316.
53.
YOSHIDAS., BUSTR., ABEK., SANTISOM., and GINSBERGM.D. (1985). Compression-induced brain edema in rats: Effect of dietary vitamin E on membrane damage in the brain. Neurology35, 126–130.
54.
YOUNGW., and FLAMME.S. (1982). Effect of high-dose corticosteroid therapy on blood flow, evoked potential, and extracellular calcium in experimental spinal injury. J. Neurosurg.57, 667–673.
