Advertisement

Bicuculline-Induced Seizures: A Challenge for Optical and Biochemical Modeling of the Cytochrome Oxidase CuA Nirs Signal

  • Chris E. Cooper
  • Mark Cope
  • Clare E. Elwell
  • David T. Delpy
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 645)

Abstract

The effect of seizures on brain blood flow and metabolism has been extensively studied. However, few studies have focused on mitochondria. We used near infrared spectroscopy (NIRS) to study hemoglobin and cytochrome oxidase changes during seizures, induced by the GABA antagonist bicuculline, in the adult rat. A broadband spectroscopy system was used with the optodes placed across the rat head. We focused on the initial seizures post-bicuculline addition during which oxyhemoglobin (HbO2) increased, deoxyhemoglobin (HHb) decreased and total hemoglobin (Hbtot) increased. The NIRS signal associated with the oxidised CuA centre of mitochondrial cytochrome coxidase (oxCCO) decreased. At the highest bicuculline doses (0.25 mg/animal) the maximum values recorded were: ΔHbO2 = +19 ± 7 μM; ΔHHb = -12 ± 4 μM; ΔHbtot = +7 ± 4 μM, ΔoxCCO = - 1.7 ± 0.3 μM. These results are broadly in line with other NIRS studies. However, previous measurements of NADH fluorescence indicate oxidationof the mitochondrial redox chain under these conditions. The changes induced by bicuculline provide an interesting challenge to the physics and biochemistry of using NIRS to study mitochondrial redox states in vivo and we explore the possible spectroscopic and/or biochemical meaning of these apparent anomalies.

Keywords

Cytochrome Oxidase Near Infrared Spectroscopy Brain Blood Flow Paracoccus Denitrificans NIRS Signal 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    F. F. Jöbsis, Non-invasive infrared monitoring of cerebral and myocardial oxygen sufficiency and circulatory parameters, Science 198, 1264-1267 (1977).PubMedCrossRefGoogle Scholar
  2. 2.
    C. E. Cooper, S. J. Matcher, J. S. Wyatt, M. Cope, G. C. Brown, E. M. Nemoto, and D. T. Delpy, Near infrared spectroscopy of the brain: relevance to cytochrome oxidase bioenergetics, Biochem. Soc. Trans. 22, 974-980 (1994).PubMedGoogle Scholar
  3. 3.
    F. Malatesta, F. Nicoletti, V. Zickermann, B. Ludwig, and M. Brunori, Electron entry in a CuA mutant of cytochrome c oxidase from Paracoccus denitrificans. Conclusive evidence on the initial electron entry metal center, FEBS Lett. 434, 322-324 (1998).PubMedCrossRefGoogle Scholar
  4. 4.
    C. E. Cooper, M. Cope, R. Springett, P. Amess, J. Penrice, L. Tyszczuk, S. Punwani, R. Ordidge, J. Wyatt, and D. T. Delpy, Use of mitochondrial inhibitors to demonstrate that cytochrome oxidase near-infrared spectroscopy can measure mitochondrial dysfunction non-invasively in the brain, J. Cereb. Blood Flow Metab. 19, 27-38 (1999).PubMedCrossRefGoogle Scholar
  5. 5.
    R. Springett, J. Newman, D. T. Delpy, and M. Cope, Oxygen dependency of cerebral CuA redox state during increased oxygen consumption produced by infusion of a mitochondrial uncoupler in newborn piglets, Adv. Exp. Med. Biol. 471, 181-188 (1999).PubMedGoogle Scholar
  6. 6.
    B. S. Meldrum and B. Nilsson, Cerebral blood flow and metabolic rate early and late in prolonged epileptic seizures induced in rats by bicuculline, Brain 99, 523-542 (1976).PubMedCrossRefGoogle Scholar
  7. 7.
    M. Cope, D. T. Delpy, J. S. Wyatt, S. C. Wray, and E. O. R. Reynolds, A CCD spectrometer to quantitate the concentration of chromophores in living tissue utilising the water absorption peak of water at 975nm, Adv. Exp. Med. Biol. 247, 33-41 (1989).Google Scholar
  8. 8.
    M. Cope. The application of near infrared spectroscopy to non-invasive monitoring of cerebral oxygenation in the newborn infant (PhD): University of London, 1991.Google Scholar
  9. 9.
    M. Cope, P. van der Zee, M. Essenpreis, S. R. Arridge, and D. T. Delpy, Data analysis methods for near infrared spectroscopy of tissue: problems in determining the relative cytochrome aa3 concentration, Proc. SPIE 1431, 251-262 (1991).CrossRefGoogle Scholar
  10. 10.
    I. Tachtsidis, M. Tisdall, T. S. Leung, C. E. Cooper, D. T. Delpy, M. Smith, and C. E. Elwell, Investigation of in vivo measurement of cerebral cytochrome-c-oxidase redox changes using near-infrared spectroscopy in patients with orthostatic hypotension, Physiol. Meas. 28, 199-211 (2007).PubMedCrossRefGoogle Scholar
  11. 11.
    M. Essenpreis, C. E. Elwell, P. van der Zee, S. R. Arridge, and D. T. Delpy, Spectral dependance of temporal point spread functions in human tissues, Applied Optics 32, 418-425 (1993).CrossRefGoogle Scholar
  12. 12.
    S. J. Matcher, C. E. Elwell, C. E. Cooper, M. Cope, and D. T. Delpy, Performance Comparison of Several Published Tissue Near-Infrared Spectroscopy Algorithms, Anal. Biochem. 227, 54-68 (1995).PubMedCrossRefGoogle Scholar
  13. 13.
    M. Yanagida and M. Tamura, Changes in oxygenation states of rat brain tissues during glutamate-related epileptic seizures–near-infrared study, Ad.v Exp. Med. Biol. 345, 579-586 (1994).Google Scholar
  14. 14.
    M. Banaji, A generic model of electron transport in mitochondria, J. Theor. Biol. 243, 501-516 (2006).PubMedCrossRefGoogle Scholar
  15. 15.
    B. Chance and G. R. Williams, Respiratory enzymes in oxidative phosphorylation. III. The steady state, J. Biol. Chem. 217, 409-427 (1955).PubMedGoogle Scholar
  16. 16.
    C. E. Cooper, Nitric oxide and cytochrome oxidase: substrate, inhibitor or effector?, Trends Biochem. Sci. 27, 33-39 (2002).PubMedCrossRefGoogle Scholar
  17. 17.
    A. Mayevsky and G. G. Rogatsky, Mitochondrial function in vivo evaluated by NADH fluorescence: from animal models to human studies, Am. J. Physiol. Cell Physiol. 292, C615-C640 (2007).PubMedCrossRefGoogle Scholar
  18. 18.
    E. Lothman, J. Lamanna, G. Cordingley, M. Rosenthal, and G. Somjen, Responses of electrical potential, potassium levels, and oxidative metabolic activity of the cerebral neocortex of cats, Brain Res. 88, 15-36 (1975).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Chris E. Cooper
    • 1
  • Mark Cope
    • 2
  • Clare E. Elwell
    • 2
  • David T. Delpy
    • 2
  1. 1.Department of Biological SciencesUniversity of EssexWivenhoe ParkUK
  2. 2.Department of Medical Physics and BioengineeringMalet Place Engineering Building, University College LondonGower StreetUK

Personalised recommendations