Cerebral Cortex Physiological Mapping in Health and Disease: From Animal Models to Clinical Applications
DOI:
https://doi.org/10.14738/bjhr.1205.19549Keywords:
Brain metabolism, NADH Redox State, Tissue energy balance, NADH Fluorescence, In Vivo monitoring of mitochondrial NADHAbstract
Normal brain cortical activity is an integration of many biochemical and physiological processes including hemodynamic, metabolic, ionic homeostasis and electrical activities. In order to evaluate the functional state of the brain, it is necessary to monitor in real time as many parameters as possible. We developed the concept of “Cerebral Cortex Physiological Mapping” that describes the interrelations between the various parameters measured by the multiparametric monitoring system (MPA). We used these systems in experimental animal models as well as in neurosurgical patients. Our approach aims are to monitor, in real-time, a small volume of the cerebral cortex containing all the tissue elements that are parts of a typical functioning brain tissue. We are interested in the microenvironment of the brain containing neurons, glia, synapses and the microcirculatory elements (small arterioles and capillaries). The various parameters and the technology developed are presented in the attached figure. During the development process we pursued the goal of being minimally invasive in terms of the penetration to the cortical tissue itself. It was obvious that the various probes could not monitor the same volume of tissue due to the size of each probe used. Therefore, we attempted to minimize the diameter of the various probes located in the MPA that had a 5-6 mm contact area with the cerebral cortex. In most of the perturbations used, such as global ischemia, anoxia, hypoxia or hemorrhage, most of the areas in the cortex will respond in the same way. We used these monitoring system in experimental animal models exposed to pathophysiological conditions. Changes in oxygen supply were induced by hypoxia, ischemia or hypeoxia. The level of brain activity was changed by epilepsy or cortical spreading depression. The key monitored parameter, in all monitoring systems, was the oxidation-reduction state of NADH, representing the mitochondrial function in vivo and in real-time. This parameter provided information on oxygen supply as well as oxygen balance in the brain. In the current review, the various systems developed since 1972 will be presented including a typical record of the results obtained.
References
Chance, B. and Williams, G. R. (1955) Respiratory enzymes in oxidative phosphorylation (III- The steady state). J. Biol. Chem. 217, 409-427,
Chance, B. and Williams, G. R. (1955) Respiratory enzymes in oxidative phosphorylation (IV- The respiratory chain). J. Biol. Chem. 217, 429-438,
Chance, B., Williams, G. R., Holmes, W. F. and Higgins, J. (1955) Respiratory enzymes in oxidative phosphorylation (V- A mechanism for oxidative phosphorylation). J. Biol. Chem. 217, 439-451,
Chance, B. and Williams, G. R. (1955) A method for the localization of sites for oxidative phosphorylation. Nature. 176, 250-254,
Harden, A. and Young, W. (1906) Alcoholic ferment of yeast-juice Part II Co-ferment of yeast-juice. Proc. Roy Soc. B78, 369-375,
Harden, A. and Young, W. J. (1905) The influence of phosphates on the fermentation of glucose by yeastjuice: preliminary communication. Proc. Chem. Soc. (London). 21, 189-191,
Warburg, O., Christian, W. and Griese, A. (1935) Wasserstoff-Ubertragendes Co-ferment, seine Zusamensetzung und Wirkungsweise. Biochem. Zeitschrift. 282, 157,
Chance, B., Cohen, P., Jobsis, F. and Schoener, B. (1962) Intracellular oxidation-reduction states in vivo. Science. 137, 499-508, ^GR; NADH 184 Mayevsky, A. (2025). Cerebral Cortex Physiological Mapping in Health and Disease: From Animal Models to Clinical Applications. British Journal of
Kohen, E., Kohen, C. and Thorell, B. (1969) Use of microfluorimetry to study the metabolism of intact cells. Biomed. Eng., 554-565, ^GR; NADH
Mayevsky, A. and Barbiro-Michaely, E. (2013) Shedding light on mitochondrial function by real time monitoring of NADH fluorescence: I. Basic methodology and animal studies. J. Clin. Monit. Comp. 27, 1-34,
Theorell, H. and Bonnichsen, R. (1951) Studies on liver alcohol dehydrogenase I. Equilibria and initial reaction velocities. Acta Chem. Scand. 5, 1105-1126,
Theorell, H. and Chance, B. (1951) Studies on liver alcohol dehydrogenase II. The kinetics of the compound of horse liver alcohol dehydrogenase and reduced diphosphopyridine nucleotide. Acta Chem. Scand. 5, 1127-1144,
Chance, B. (1951) Enzyme-substrate compounds. Adv. in Enzymology, 153-190,
Chance, B. and Legallias, V. (1951) Rapid and sensetive spectrophotometry. II. A stopped-flow attachment for a stabilized quartz spectrophotometer. Rev. Sci. Instr. 22, 627-638,
Chance, B. (1952) Spectra and reaction kinetics of respiratory pigments of homogenized and intact cells. Nature. 169, 215-221,
Chance, B. (1952) Respiratory pigments of metabolism cells. Federation Proc. 11,
Chance, B. and Neilands, J. B. (1952) Studies on lactic dehydrogenase of heart. II. A compound of lactic dehydrogenase and reduced pyridine nucleotide. J. Biol. Chem. 199, 383-387,
Chance, B. and Castor, L. N. (1952) Some patterns of the respiratory pigments of ascites tumors of mice. Science. 116, 200-202,
Chance, B. and Williams, G. R. (1954) Steady-state of reduced pyridine nucleotides in phosphorylating rat liver mitochondria. Am. Soc. Biol. Chem. 13. Abstract 633,
Connelly, C. M. and Chance, B. (1954) Kinetics of reduced pyridine nucleotides in stimulated frog muscle and nerve. Am. Physiol. Soc. 13, 29-,
Chance, B. (1954) Enzyme mechanisms in living cells. (McElroy, W. D. and Glass, B., eds.). pp. 399-453, Johns Hopkins Press, Baltimore
Chance, B. (1954) Spectrophotometry of intracellular respiratory pigments. Science. 120, 767-775,
Chance, B. and Williams, G. R. (1955) Respiratory enzymes in oxidative phosphorylation (I- Kinetics of oxygen utilization). J. Biol. Chem. 217, 383-393,
Chance, B. and Williams, G. R. (1955) Respiratory enzymes in oxidative phosphorylation (II- Difference spectra). J. Biol. Chem. 217, 395-407,
Chance, B. and Williams, G. R. (1956) The respiratory chain and oxidative phosphorylation. In Advances in Enzymology (Nord, F. F., ed.). pp. 65-134, Interscience Publisher, Inc., New York
Chance, B. and Connelly, C. M. (1957) A method for the estimation of the increase in concentration of adenosine diphosphate in muscle sarcosomes following a contraction. Nature. 179, 1235-1237, ^GR;
Chance, B. (1957) Techniques for the assay of the respiratory enzymes. (Colowick, S. P. and Kaplan, N. O., eds.). pp. 273-329, Academic Press, New York
Chance, B. (1957) Cellular oxygen requirements. Fed. Proc. 16, 671-680, ^GR; NADH
Chance, B. (1959) The response of mitochondria to muscular contraction. Ann. N.Y. Acad. Sci. 81, 477-489, ^GR; NADH
Chance, B. and Hollunger, G. (1957) Succinate-linked pyridine nucleotide reduction in mitochondria. In Federation Proceedings, Abstract 703
Chance, B., Perry, R., Akerman, L. and Thorell, B. (1959) Highly sensitive recording microspectrophotometer. Rev. Sci. Instr. 30, 735-741, ^GR; NADH 185
Theorell, H. and Nygaard, A. P. (1954) Kinetics and equilibria in flavoprotein systems. II. The effects of pH, anions and temperature on the dissociation and reassociation of the old yellow enzyme. Acta Chem Scand. 8, 1649-1658,
Theorell, H. and Nygaard, A. P. (1954) Kinetics and equilibria in flavoprotein systems I. A fluorescence recorder and its application to a study of the dissociation of the old yellow enzyme and its resynthesis from riboflavin phosphate and protein. Acta Chem Scand. 8, 877-888,
Theorell, H., Nygaard, A. P. and Bonnichsen, R. (1954) Kinetics of alcohol dehydrogenases, studies with the aid of a fluorescence recorder. Acta Chem. Scand. 8, 1490-1491,
Boyer, P. D. and Theorell, H. (1956) The change in reduced diphosphopyridine nucleotide (DPNH) fluorescence upon combination with liver alcohol dehydrogenase (ADH). Acta Chem. Scand. 10, 447-450, ^GR; nadh
Duysens, L. N. M. and Amesz, J. (1957) Fluorescence spectrophotometry of reduced phosphopyridine nucleotide in intact cells in the near-ultraviolet and visible region. Biochim. Biophys. Acta. 24, 19-26, ^GR;
Chance, B., Conrad, H. and Legallias, V. (1958) Simultaneous fluorimetric and spectrophotometric measurements of reaction kinetics of bound pyridine nucleotide in mitochondria. ed.)^eds.). p. 44, Paper presented at the The Biophysical Society Meeting, Cambridge, Mass. p. 44.
Chance, B. and Baltscheffsky, H. (1958) Respiratory enzymes in oxidative phosphorylation (VII - Binding of intramitochondrial reduced pyridine nucleotide). J. Biol. Chem. 233, 736-739, ^GR; NADH
Klingenberg, M., Slenczka, W. and Ritt, E. (1959) Vergleichende biochemie der pyridinnucleotid-systeme in mitochondrien verschiedener organe. Biochemische Zeitschrift. 332, 47-66, ^GR; NADH
Chance, B. (1959) Quantitative aspects of the control of oxygen utilization. In Ciba Foundation Symposium on Cell Metabolism ed.)^eds.). pp. 91-129, J. & A. Churchill Ltd. London, pp 91-129.
Chance, B. and Legallias, V. (1959) Differential microfluorimeter for the localization of reduced pyridine nucleotide in living cells. Rev. Sci. Instr. 30, 732-735, ^GR; NADH
Perry, R. P., Thorell, B., Akerman, L. and Chance, B. (1959) Localization and assay of respiratory enzymes in single living cells. Absorbency measurements on the Nebenkern. Nature. 184, 929-931, ^GR; NADH
Chance, B. and Thorell, B. (1959) Fluorescence measurements of mitochondrial pyridine nucleotide in aerobiosis and anaerobiosis. Nature. 184, 931-934, ^GR; NADH
Thorell, B. and Chance, B. (1959) Absorbancy measurements on liver and kidney cells. Nature. 184, 934-
Chance, B. and Jobsis, F. (1959) Changes in fluorescence in a frog sartorius muscle following a twitch. Nature. 184, 195-196, ^GR; NADH
Chance, B. and Thorell, B. (1959) Localization and kinetics of reduced pyridine nucleotide in living cells by microfluorometry. J. Biol. Chem. 234, 3044-3050, ^GR; NADH
Chance, B. and Hollunger, G. (1960) Energy-linked reduction of mitochondrial pyridine nucleotide. Nature. 185, 666-672, ^GR; NADH
Chance, B., Schoener, B. and Fergusson, J. J. (1962) In vivo induced oxidation by adrenocorticotrophic hormone of reduced pyridine nucleotide in the adrenal cortex of hypophysectomized rats. Nature. 195, 776-778, ^GR; NADH
Chance, B. and Schoener, B. (1962) Correlation of oxidation-reduction changes of intracellular reduced pyridine nucleotide and changes in electro-encephalogram of the rat in anoxia. Nature. 195, 956-958, ^GR;
Chance, B., Legallias, V. and Schoener, B. (1962) Metabolically linked changes in fluorescence emission spectra of cortex of rat brain, kidney and adrenal gland. Nature. 195, 1073-1075, ^GR; NADH Mayevsky, A. (2025). Cerebral Cortex Physiological Mapping in Health and Disease: From Animal Models to Clinical Applications. British Journal of
Chance, B., Mayer, D. and Rossini, L. (1970) A time-sharing instrument for direct readout of oxidationreduction states in intracellular compartments of cardiac tissue. IEEE Trans. Biomed. Eng. BME-17, 118-
Chance, B., Graham, N. and Mayer, D. (1971) A time sharing fluorometer for the readout of intracellular oxidation-reduction states of NADH and flavoprotein. Rev. Scientific Instr. 42, 951-957, ^GR; NADH
Chance, B. (1966) The identification and control of metabolic states. Genootschap ter Bevordering van Natuur-, Genees-, en Heelkunde te Amsterdam, 5-37, ^GR; NADH;6144
Chance, B. and Schoener, B. (1965) A correlation of absorption and fluorescence changes in ischemia of the rat liver, in vivo. Biochemische Zeitschrift. 341, 340-345, ^GR; NADH
Chance, B., Williamson, J. R., Jamieson, D. and Schoener, B. (1965) Properties and kinetics of reduced pyridine nucleotide fluorescence of the isolated and in vivo rat heart. Biochemische Zeitschrift. 341, 357-
Chance, B. (1967) Biochemical studies of transitions from rest to activity. The Williams & Wilkins Company, Baltimore
Chance, B., Schoener, B. and Schindler, F. (1963) The intracellular oxidation-reduction state. (Dickens, F. and Neil, E., eds.). pp. 367-392, Pergamon Press, London
Mayevsky, A. (1984) Brain NADH redox state monitored in vivo by fiber optic surface fluorometry. Brain Res. Rev. 7, 49-68, ^6077; 6149; 6088; 6207
Mayevsky, A. and Chance, B. (1982) Intracellular oxidation-reduction state measured in situ by a multicannel fiber-optic surface fluorometer. Science. 217, 537-540,
Chance, B., Oshino, N., Sugano, T. and Mayevsky, A. (1973) Basic principles of tissue oxygen determination from mitochondrial signals. Adv. Exp. Med. Biol.,. 37A, 277-292, ^GR; NADH
Lubbers, D. W. (1995) Optical sensors for clinical monitoring. Acta Anaesth. Scand. Suppl. 39, 37-54, ^GR;
Mayevsky, A., et al. (1990) Oxygen supply and brain function in vivo: a multiparametric monitoring approach in the Mongolian gerbil. In Oxygen Transport to Tissue XII (Piper, J., Goldstick, T. K. and Meyer, M., eds.). pp. 303-313, Plenum Pub.
Rampil, I. J., Litt, L. and Mayevsky, A. (1992) Correlated, simultaneous, multiple-wavelength optical monitoring in vivo of localized cerebrocortical NADH and brain microvessel hemoglobin oxygen saturation. J. Clin. Monit. 8, 216-225,
Stern, M. D., et al. (1977) Continuous measurement of tissue blood flow by laser-Doppler spectroscopy. Am. J. Physiol. 232, H441-448,
Haberl, R. L., Heizer, M. L., Marmarou, A. and Ellis, E. F. (1989) Laser-Doppler assessment of brain microcirculation: effect of systemic alterations. Am J Physiol Heart Circ Physiol. 256, H1247-1254,
Dirnagl, U., Kaplan, B., Jacewicz, M. and Pulsinelli, W. (1989) Continuous measurement of cerebral cortical blood flow by laser-Doppler flowmetry in a rat stroke model. J. CBF Metab. 9, 589-596,
Mayevsky, A., et al. (2001) Assessment of transplanted kidney vitality by a multiparametric monitoring system. Transplant. Proc. 33, 2933-2934,
Mayevsky, A., et al. (1999) Optical monitoring of NADH redox state and blood flow as indicators of brain energy balance. Adv. Exp. Med. Biol. 471, 133-140,
Barbiro-Michaely, E., Zurovsky, Y. and Mayevsky, A. (1998) Real time monitoring of rat liver energy state during ischemia. Microvasc. Res. 56, 253-260,
Mayevsky, A. and Rogatsky, G. (2007) Mitochondrial function in vivo evaluated by NADH fluorescence: From animal models to human studies. Am. J. Physiol. Cell Physiol. 292, C615-C640,
Mayevsky, A., et al. (1999) Brain viability and function analyzer: multiparametric real-time monitoring in neurosurgical patients. Acta Neurochir. Suppl (Wien.). 75, 63-66, 187
Sonn, J. and Mayevsky, A. (2000) Effects of brain oxygenation on metabolic, hemodynamic, ionic and electrical responses to spreading depression in the rat. Brain Res. 882, 212-216,
Mayevsky, A., et al. (2002) The evaluation of brain CBF and mitochondrial function by a fiber optic tissue spectroscope in neurosurgical patients. Acta Neurochir. Suppl. 81, 367-371,
Mayevsky, A. and Chance, B. (1973) A new long-term method for the measurement of NADH fluorescence in intact rat brain with implanted cannula. Adv. Exp. Med. Biol. 37A, 239-244,
Mayevsky, A., Sonn, J. and Barbiro-Michaely, E. (2013) Physiological mapping of brain functions in vivo: Surface monitoring of hemodynamic metabolic ionic and electrical activities in real-time. J. Neurosci. Neuroeng. 2, 150-177,
Mayevsky, A. (1984) Brain oxygen toxicity. Invited Review. In 8th Symp. Under-water Physiol. (Bachrach, A. J. and Matzen, M. M., ed.)^eds.). pp. 69-89, Undersea Medical Society Inc, Bethesda, Maryland
Mayevsky, A. and Bar-Sagie, D. (1978) The interrelation between CBF, energy metabolism and ECoG in a new awake brain model. Adv. Exp. Med. Biol. 92, 761-768, ^GR; NADH
Mayevsky, A., Lebourdais, S. and Chance, B. (1980) The interrelation between brain PO2 and NADH oxidation- reduction state in the gerbil. J. Neurosci. Res. 5, 173-182, ^GR; NADH; SD
Mayevsky, A. (1975) The effect of trimethadione on brain energy metabolism and EEG activity of the conscious rat exposed to HPO. J. Neurosci. Res. 1, 131-142, ^GR; NADH
Friedli, C. M., Sclarsky, D. S. and Mayevsky, A. (1982) Multiprobe monitoring of ionic, metabolic, and electrical activities in the awake brain. Am. J. Physiol. 243, R462-469,
Crowe, W., Mayevsky, A. and Mela, L. (1977) Application of a solid membrane ion selective electrode to in vivo measurements. Am. J. Physiol. 233, C56-C60,
Mayevsky, A., et al. (1995) Multiparametric monitoring of the awake brain exposed to carbon monoxide. J. Appl. Physiol. 78, 1188-1196, ^6088; 6207; 6097
Mayevsky, A. (1983) Multiparameter monitoring of the awake brain under hyperbaric oxygenation. J. Appl. Physiol. 54, 740-748,
Mayevsky, A., et al. (1992) Multiparametric evaluation of brain functions in the Mongolian gerbil in vivo. J. Basic Clin. Physiol. Pharmacol. 3, 323-342, ^6153; ysonn; 7171
Mayevsky, A., Flamm, E. S., Pennie, W. and Chance, B. (1991) A fiber optic based multiprobes system for intraoperative monitoring of brain functions. SPIE. 1431, 303-313,
Frank, K. H., Kessler, M., Appelbaum, K. and Dummler, W. (1989) The Erlangen micro-lightguide spectrophotometer EMPHO I. Phys. Med. Biol. 34, 1883-1900, +
Mayevsky, A. and Sclarsky, D. S. (1983) Correlation of brain NADH redox state, K , PO and electrical activity during hypoxia, ischemia and spreading depression. Adv. Exp. Med. Biol. 159, 129-141, ^GR; NADH; SD
Mayevsky, A., Friedli, C. M. and Reivich, M. (1985) Metabolic, ionic and electrical responses of the gerbil brain to ischemia. Am. J. Physiol. 248, R99-R107, ^6088; 7059
Mayevsky, A., et al. (1996) Cortical spreading depression recorded from the human brain using a multiparametric monitoring system. Brain Res. 740, 268-274,
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Avraham Mayevsky
This work is licensed under a Creative Commons Attribution 4.0 International License.
