Skip to main content
SpringerLink
Log in

Redox Changes in Perfusates Following Intracerebral Penetration of Microdialysis Probes

  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Microdialysis probe insertion into rat cerebral cortex significantly affects the levels of redox-active substances in brain extracellular fluid. Ascorbic acid levels are high immediately after probe insertion, decline rapidly, and then rise as the rat recovers from anesthesia 5–8 hours after surgery. Uric acid is at a low level for 5 hours and then rapidly increases in parallel with ascorbic acid. High ascorbic acid levels immediately after probe insertion are likely due to a shift from intracellular to extracellular fluids, whereas the delayed increase in uric acid may be due to increased enzymatic formation. After removal from the brain, hydrogen peroxide (H2O2) in microdialysis samples produces catalase-sensitive oxidative chemiluminescence. Microdialysis samples also produce high level catalase-resistant chemiluminescence associated with ascorbic acid levels after penetration injury. Although ascorbic acid is likely an antioxidant at concentrations estimated to be in brain extracellular fluid, it may have prooxidant effects when complexed with transition metals released into the neuronal microenvironment during traumatic brain injury.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Pazdernik, T. L., Layton, M. E., Nelson, S. R., and Samson, F. E. 1992. The osmotic/calcium stress theory of brain damage: are free radicals involved? Neurochem. Res. 17:11–21.

    Google Scholar 

  2. Bondy, S. C. 1995. The relation of oxidative stress and hyperexcitation to neurological disease. Proc. Soc. Exp. Biol. Med. 208(4):337–45.

    Google Scholar 

  3. Amberg, G., and Lindefors, N. 1989. Intracerebral microdialysis: II. Mathematical studies of diffusion kinetics. J. Pharmacol. Meth. 22(3):157–83.

    Google Scholar 

  4. Benveniste, H., and Hüttemeier, P. C. 1990. Microdialysis-theory and application. Prog. Neurobiol. 35:195–215.

    Google Scholar 

  5. Halliwell, B, and Gutteridge, J. M. C. 1990. The antioxidants of human extracellular fluids. Arch. Biochem. Biophys. 280:1–8.

    Google Scholar 

  6. Frei, B., Stocker, R., and Ames, B. N. 1992. Small molecule antioxidant defenses in human extracellular fluids. Curr. Comm. Cell Mol. Biol. 5:23–45.

    Google Scholar 

  7. Krause, G. S., Nayini, N. R., White, B. C., Hoenher, T. J., Garritano, A. M., O'Neill, B. J., and Aust, S. D. 1987. Natural course of iron delocalization and lipid peroxidation during the first eight hours following a 15-minute cardiac arrest in dogs. Ann. Emerg. Med. 16:1200–1205.

    Google Scholar 

  8. Patt, A., Harken, A. H., Burton, L. K., Rodell, T. C., Piermattei, D., Schorr, W. J., Parker, N. B., Berger, E. M.; Horesh, I. R., Terada, L. S., Linas, S. L., Cheronis, J. C., and Repine, J. E. 1988. Xanthine oxidase-derived hydrogen peroxide contributes to ischemia reperfusion-induced edema in gerbil brains. J. Clin. Invest. 81:1556–1562.

    Google Scholar 

  9. Simonson, S. G., Zhang, J., Canada, A. T., Jr., Su, Y.-F., Benveniste, H., and Piantadosi, C. A. 1993. Hydrogen peroxide production by monoamine oxidase during ischemia-reperfusion in the rat brain. J. Cereb. Blood Flow Metab. 13:125–134.

    Google Scholar 

  10. Hyslop, P. A., Zhang, Z., Pearson, D. V., and Phebus, L. A. 1995. Measurement of striatal H2O2 by microdialysis following global forebrain ischemia and reperfusion in the rat: correlation with the cytotoxic potential of H2O2 in vitro. Brain Res. 671:181–186.

    Google Scholar 

  11. Davies, K. J. A., Sevanian, A., Muakkassah Kelly, S. F., and Hochstein, P. 1986. Uric acid-iron ion complexes. A new aspect of the antioxidant functions of uric acid. Biochem. J. 235:747–754.

    Google Scholar 

  12. Ames, B. N., Cathcart, R., Schwiers, E., and Hochstein, P. 1981. Uric acid provides an antioxidant defense in humans against oxidant-and radical-caused aging and cancer: a hypothesis. Proc. Natl. Acad. Sci. U.S.A. 78:6858–6862.

    Google Scholar 

  13. Rosenbloom, F. M., Kelley, W. N., Miller, J., Henderson, J. F., and Seegmiller, J. E. 1967. Inherited disorder of purine metabolism. Correlation between central nervous system disfunction and biochemical defects. JAMA 202:175–177.

    Google Scholar 

  14. Hillered, L., Persson, L., Bolander, H. G., Hallström, Ä., and Ungerstedt, U. 1988. Increased extracellular levels of ascorbic acid in the striatum after middle cerebral artery occlusion in the rat monitored by intracerebral microdialysis. Neurosci. Lett. 95:286–290.

    Google Scholar 

  15. Hillered, L., Nilsson, P., Ungerstedt, U., and Ponten, U. 1990. Trauma-induced increase of extracellular ascorbic acid in rat cerebral cortex. Neurosci. Lett. 113:328–332.

    Google Scholar 

  16. Nihei, H., Kanemitsu, H., Tamura, A., Oka, H., and Sano, K. 1989. Cerebral uric acid, xanthine, and hypoxanthine after ischemia: the effect of allopurinol. Neurosurgery 25:613–617.

    Google Scholar 

  17. O'Neill, R. D., Gonzalez-Mora, J.-L., Boutelle, M. G., Ormonde, D. E., Lowry, J. P., Duff, A., Fumero, B., Fillenz, M., and Mas, M. 1991. Anomalously high concentrations of brain extracellular uric acid detected with chronically implanted probes: implications for in vivo sampling techniques. J. Neurochem. 57:22–29.

    Google Scholar 

  18. Landolt, H., Lutz, T. W., Langemann, H., Stäuble, D., Mendelowitsch, A., Gratzl, O., and Honegger, C. G. 1992. Extracellular antioxidants and amino acids in the cortex of the rat: monitoring by microdialysis of early ischemic changes. J. Cereb. Blood Flow Metab. 12:96–102.

    Google Scholar 

  19. Paxinos, G., and Watson, C. (Ed.). 1986. The Rat Brain in Stereotaxic Coordinates (2nd ed.). North Ryde, NSW, Australia: Academic Press Australia, Figure 25.

    Google Scholar 

  20. Omaye, S. T., Schaus, E. E., Kutnink, M. A., and Hawkes, W. C. 1987. Measurement of vitamin C in blood components by high-performance liquid chromatography. Implication in assessing vitamin C status. Ann. N.Y. Acad. Sci. 498(389):389–401.

    Google Scholar 

  21. Layton, M. E., Wood, J. G., Yan, Z., and Forster, J. 1996. Ischemia/reperfusion alters uric acid and ascorbic acid levels in liver. J. Surg. Res. 64(1):1–5.

    Google Scholar 

  22. Yamamoto, Y., Frei, B., and Ames, B. 1990. Assay of lipid hydroperoxides using high performance liquid chromatography with isoluminol chemiluminescence detection. Meth. Enzymol. 186: 371–380.

    Google Scholar 

  23. Frei, B., Yamamoto, Y., Niclas, D., and Ames, B.N. 1988. Evaluation of an isoluminol chemiluminescence assay for the detection of hydroperoxides in human blood plasma. Anal. Biochem. 175(1):120–30.

    Google Scholar 

  24. Davison, A. J., Kettle, A. J., and Fatur, D. J. 1986. Mechanism of the inhibition of catalase by ascorbic acid. J. Biol. Chem. 261(3):1193–1200.

    Google Scholar 

  25. Reed, G. A., and Madhu, C. 1987. Peroxidase scavenging by Cu (II) sulfate and Cu (II) [3,5-disopropylsalicylate]2. Pages 287–298, in Sorenson, John C. (ed.), Biology of Copper Complexes, Humana Press, Clifton, NJ.

    Google Scholar 

  26. Hwang, H., and Dasgupta, P.K. 1986. Fluorometric flow injection determination of aqueous peroxides at nanomolar level using membrane reactors. Anal. Chem. 58:1521–1524.

    Google Scholar 

  27. Milby, K., Oke, A., and Adams, R. N. 1982. Detailed mapping of ascorbic acid distribution in rat brain. Neuroscience Letters 28: 15–20.

    Google Scholar 

  28. Grünewald, R.A. 1993. Ascorbic acid in the brain. Brain. Res. Rev. 18:123–133.

    Google Scholar 

  29. Penkowa, M., and Moos, T. 1995. Disruption of the blood-brain interface in neonatal rat neocortex induces a transient expression of metallothionein in reactive astrocytes. Glia 13(3):217–27.

    Google Scholar 

  30. Parks, D. A., Williams, T. K., and Beckmann, J. S. 1988. Conversion of xanthine dehydrogenase to oxidase in ischemic rat intestine: a reevaluation. Am. J. Physiol. 254(G17):G768–G774.

    Google Scholar 

  31. Battelli, M.G., Buonamici, L., Abbondonza, A., Virgili, M., Contestabile, A., and Stirpe, F. 1995. Excitotoxic increase of xanthine dehydrogenase and xanthine oxidase in the rat olfactory cortex. Brain Res. Devel. Brain. Res. 86:340–344.

    Google Scholar 

  32. McCord, J., and Fridovich, I. 1968. The reduction of cytochrome c by milk xanthine oxidase. J. Biol. Chem. 213(21):5753–5760.

    Google Scholar 

  33. Hunt, J., and Massey, V. 1992. Purification and properties of milk xanthine dehydrogenase. J. Biol. Chem. 267:21479–21485.

    Google Scholar 

  34. Demediuk, P., Saunders, R. D., Anderson, D. K., Means, E. D., and Horrocks, L. A. 1985a. Membrane lipid changes in laminectomized and traumatized cat spinal cord. Proc. Natl. Acad. Sci. U.S.A. 82(20):7071–5.

    Google Scholar 

  35. Demediuk, P., Saunders, R. D., Clendenon, N. R., Means, E. D., Anderson, D. K., and Horrocks, L. A. 1985c. Changes in lipid metabolism in traumatized spinal cord. Prog. Brain Res. 63(211): 211–26.

    Google Scholar 

  36. Demediuk, P., and Faden, A. I. 1988. Traumatic spinal cord injury in rats causes increases in tissue thromboxane but not peptidoleukotrienes. J. Neurosci. Res. 20(1):115–21.

    Google Scholar 

  37. Saunders, R. D., Dugan, L. L., Demediuk, P., Means, E. D., Horrocks, L. A., and Anderson, D. K. 1987. Effects of methylprednisolone and the combination of alpha-tocopherol and selenium on arachidonic acid metabolism and lipid peroxidation in traumatized spinal cord tissue. J. Neurochem. 49(1):24–31.

    Google Scholar 

  38. Asano, T. Koide, T., Gotoh, O., Joshita, H., Hanamura, T., Shigeno, T., and Takakura, K. 1989. The role of free radicals and eicosanoids in the pathogenic mechanism underlying ischemic brain edema. Mol. Chem. Neuropathol. 10:101–133.32.

    Google Scholar 

  39. Prat, A. G., and Turrens, J. F. 1990. Ascorbic acid-and hemoglobin-dependent brain chemiluminescence. Free Radic. Biol. Med. 8(4):319–25.

    Google Scholar 

  40. Chance, B. 1949. The properties of the enzyme-substrate compounds of horseradish peroxidase and peroxides. III. The reaction of compound II with ascorbic acid. Arch. Biochem. Biophys. 24: 389–409.

    Google Scholar 

  41. Romanas, M.M., Samson, F.E., Nelson, S.K., and Pazdernik, T.L. 1995. Hydroxyl radicals in human cerebrospinal fluid. International Congress of Toxicology-VII, 9-P2.

  42. Martell, A.E. 1982. Chelates of ascorbic acid. Formation and catalytic properties. Pages 153–178, in Seib, P.A., and Tolbert, B.M. (eds.), Ascorbic Acid: Chemistry, Metabolism, and Uses. Advances in chemistry series, 200, American Chemical Society, Washington, D.C.

    Google Scholar 

  43. Emerson, M.R., Samson, F.E., and Pazdernik, T.L. 1996. Evidence for an ascorbic acid-copper-peroxide complex in lipid peroxidation. Soc. Neurosci. 22:562.3.

    Google Scholar 

  44. Romanas, M.M., Emerson, M.R., Samson, F.E., Nelson, S.R., and Pazdernik, T. L. 1996. Metal-dioxygen complexes are critical in the pro-oxidant actions of ascorbate. Oxygen 96, Abstract #1-79.

  45. Sam, J.W., Tang, X.-J., and Peisach, J. 1994. Electrospray mass spectrometry of iron bleomycin: Demonstration that activated bleomycin is a ferric peroxide complex. J. Am. Chem. Soc. 116: 5250–5256.

    Google Scholar 

  46. Rabow, L.E., McGall, G.H., Stubbe, J., and Kozarich, J.W. 1990. Identification of the source of oxygen in the alkaline-labile product accompanying cytosine release during bleomycin-mediated oxidative degradation of d(CGCGCG). J. Am. Chem. Soc. 112:3203–3208.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, Toxicology and Therapeutics. Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington

    Matthew E. Layton, Jennifer K. Wagner & Thomas L. Pazdernik

  2. Smith Mental Retardation Research Center, University of Kansas Medical Center, Kansas City, Kansas

    Fred E. Samson & Thomas L. Pazdernik

Authors
  1. Matthew E. Layton
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jennifer K. Wagner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fred E. Samson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Thomas L. Pazdernik
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Layton, M.E., Wagner, J.K., Samson, F.E. et al. Redox Changes in Perfusates Following Intracerebral Penetration of Microdialysis Probes. Neurochem Res 22, 735–741 (1997). https://doi.org/10.1023/A:1027362312381

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1027362312381

Search

Navigation