Real Time In Vivo Evaluation of Mitochondrial Activity and Brain Functions during Ischemic Stroke
Main Article Content
Abstract
More than 50% of total energy consumed by the brain is utilized by active transport processes which are responsible for keeping the ionic homeostasis in the brain. Under an ischemic condition, energy availability is limited, and, as a result, inhibition of the ion pumps is unavoidable. The initial consequence of such inhibition is a gradual accumulation of K+ in the extracellular space leading to a second phase of the ischemic depolarization phenomenon. During ischemic depolarization, extracellular K+ will increase 15-20-fold, while extracellular Ca2+ is decreasing 10 fold. Another optional effect of mild ischemia is the development of Cortical Spreading Depression due to the leakage of K+ into the extracellular space. The Mongolian gerbil provides a very useful animal model to study the effects of ischemia on brain functions.
The aims of the study were as follows: (1) To elucidate the mechanism behind the development of ischemic depolarization or cortical spreading depression under unilateral and bilateral carotid artery occlusion. (2) To correlate the kinetics of the recovery processes to the level of ischemia.
We tested the correlation between energy depletion level (evaluated by intramitochondrial NADH redox state and Cerebral Blood Flow) and the development of ischemic depolarization or cortical spreading depression (evaluated by extracellular K+, H+, Ca2+, DC potential and 366 nm reflectance changes) under partial and complete ischemia using the multiparametric monitoring system.
The results could be summarized as follows: (1) Under bilateral occlusion, in all gerbils the ischemic depolarization was recorded within 1-2 min. (2) Under unilateral occlusion, the level of ischemia obtained was significantly smaller and led to the ischemic depolarization in about 60% of the gerbils. (3) The K+ leakage during the ischemic depolarization had an 'all or none' nature in terms of maximal K÷ levels and time to reach it. (4) The main effect of various lengths of bilateral occlusion was on the recovery time of extracellular K+ level. (5) Cortical spreading depression develop in most cases during the recovery from the ischemic event when ischemic depolarization was not recorded under the ischemic episode.
Article Details
How to Cite
MAYEVSKY, Avraham.
Real Time In Vivo Evaluation of Mitochondrial Activity and Brain Functions during Ischemic Stroke.
Medical Research Archives, [S.l.], v. 11, n. 6, june 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/3967>. Date accessed: 22 dec. 2024.
doi: https://doi.org/10.18103/mra.v11i6.3967.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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2. Barcroft J. The Respiratory Function of Blood. Cambridge: Cambridge University Press; 1914.
3. Fink MP. Bench-to-bedside review: Cytopathic hypoxia. Critical Care (London, England). 2002;6:491-499.
4. Robertson CL, Soane L, Siegel ZT, Fiskum G. The potential role of mitochondria in pediatric traumatic brain injury. Developmental neuroscience. 2006;28:432-446.
5. Sullivan PG, Krishnamurthy S, Patel SP, Pandya JD, Rabchevsky AG. Temporal characterization of mitochondrial bioenergetics after spinal cord injury. J Neurotrauma. 2007;24:991-999.
6. Sims NR, Anderson MF. Mitochondrial contributions to tissue damage in stroke. Neurochem Internat. 2002;40:511-526.
7. Ying W. NAD+ and NADH in cellular functions and cell death. Front Biosci. 2006;11:3129-3148.
8. Ying W. NAD+ and NADH in brain functions, brain diseases and brain aging. Front Biosci. 2007;12:1863-1888.
9. Kann O, Kovacs R. Mitochondria and neuronal activity. Am J Physiol Cell Physiol. 2007;292(2):C641-C657.
10. Edeas M, Weissig V. Targeting mitochondria: Strategies, innovations and challenges The future of medicine will come through mitochondria. Mitochondrion. 2013;13(5):389-390.
11. Chance B, Cohen P, Jobsis F, Schoener B. Intracellular oxidation-reduction states in vivo. Science. 1962;137:499-508.
12. Chance B, Oshino N, Sugano T, Mayevsky A. Basic principles of tissue oxygen determination from mitochondrial signals. Oxygen Transport to Tissue, Adv Exp Med Biol. 1973;37A:277-292.
13. Lubbers DW. Optical sensors for clinical monitoring. Acta Anaesth Scand Suppl. 1995;39(104):37-54.
14. Chance B, Williams GR. Steady-state of reduced pyridine nucleotides in phosphorylating rat liver mitochondria. Am Soc Biol Chem. 1954;13. Abstract 633.
15. Chance B, Williams GR. Respiratory enzymes in oxidative phosphorylation (III- The steady state). J Biol Chem. 1955;217:409-427.
16. Chance B, Williams GR. Respiratory enzymes in oxidative phosphorylation (I- Kinetics of oxygen utilization). J Biol Chem. 1955;217:383-393.
17. Connelly CM, Chance B. Kinetics of reduced pyridine nucleotides in stimulated frog muscle and nerve. Am Physiol Soc. 1954;13(1):29-.
18. Chance B, Jobsis F. Changes in fluorescence in a frog sartorius muscle following a twitch. Nature. 1959;184:195-196.
19. Chance B, Cohen P, Jobsis F, Schoener B. Localized fluorometry of oxidation-reduction states of intracellular pyridine nucleotide in brain and kidney cortex of the anesthetized rat. Science. 1962;136:325.
20. Chance B, Legallias V, Schoener B. Metabolically linked changes in fluorescence emission spectra of cortex of rat brain, kidney and adrenal gland. Nature. 1962;195:1073-1075.
21. Chance B, Schoener B. Correlation of oxidation-reduction changes of intracellular reduced pyridine nucleotide and changes in electro-encephalogram of the rat in anoxia. Nature. 1962;195:956-958.
22. Chance B, Schoener B. Control of oxidation-reduction state of NADH in the liver of anesthetized rats. Symp Regul Enzyme Act Synth Norm Neoplast Tissues Proc. 1963:169-185.
23. Chance B, Schoener B, Fergusson JJ. In vivo induced oxidation by adrenocorticotrophic hormone of reduced pyridine nucleotide in the adrenal cortex of hypophysectomized rats. Nature. 1962;195:776-778.
24. Mayevsky A, Chance B. A new long-term method for the measurement of NADH fluorescence in intact rat brain with implanted cannula. In: Bicher HI, Bruley DF, eds. Vol 37A. New York: Plenum Press; 1973:239-244.
25. Mayevsky A. Brain NADH redox state monitored in vivo by fiber optic surface fluorometry. Brain Res Rev. 1984;7:49-68.
26. Vatov L, Kizner Z, Ruppin E, Meilin S, Manor T, Mayevsky A. Modeling brain energy metabolism and function: A multiparametric monitoring approach. Bull Math Biol. 2006;68:275-291.
27. Mayevsky A, Barbiro-Michaely E. Shedding light on mitochondrial function by real time monitoring of NADH fluorescence: I. Basic methodology and animal studies. J Clin Monit Comp. 2013;27:1-34.
28. Mayevsky A, Barbiro-Michaely E. Shedding light on mitochondrial function by real time monitoring of NADH fluorescence: II: Human studies. J Clin Monit Comp. 2013;27:125-145.
29. Rutkai I, Merdzo I, Wunnava SV, Curtin GT, Katakam PV, Busija DW. Cerebrovascular function and mitochondrial bioenergetics after ischemia-reperfusion in male rats. J Cereb Blood Flow Metab. 2019;39(6):1056-1068.
30. Liu F, Lu J, Manaenko A, Tang J, Hu Q. Mitochondria in Ischemic Stroke: New Insight and Implications. Aging Dis. 2018;9(5):924-937.
31. Yang JL, Mukda S, Chen SD. Diverse roles of mitochondria in ischemic stroke. Redox Biol. 2018;16:263-275.
32. Sperling JA, Sakamuri S, Albuck AL, et al. Measuring Respiration in Isolated Murine Brain Mitochondria: Implications for Mechanistic Stroke Studies. Neuromolecular Med. 2019;21(4):493-504.
33. Chen W, Huang J, Hu Y, Khoshnam SE, Sarkaki A. Mitochondrial Transfer as a Therapeutic Strategy Against Ischemic Stroke. Transl Stroke Res. 2020;11(6):1214-1228.
34. An H, Zhou B, Ji X. Mitochondrial quality control in acute ischemic stroke. J Cereb Blood Flow Metab. 2021;41(12):3157-3170.
35. Yang M, He Y, Deng S, et al. Mitochondrial Quality Control: A Pathophysiological Mechanism and Therapeutic Target for Stroke. Front Mol Neurosci. 2021;14:786099.
36. Tian H, Chen X, Liao J, et al. Mitochondrial quality control in stroke: From the mechanisms to therapeutic potentials. J Cell Mol Med. 2022;26(4):1000-1012.
37. Mayevsky A, Lebourdais S, Chance B. The interrelation between brain PO2 and NADH oxidation- reduction state in the gerbil. J Neurosci Res. 1980;5:173-182.
38. Friedli CM, Sclarsky DS, Mayevsky A. Multiprobe monitoring of ionic, metabolic, and electrical activities in the awake brain. Am J Physiol. 1982;243(3):R462-469.
39. Mayevsky A, Yoles E, Zarchin N, Kaushansky D. Brain vascular ionic and metabolic responses to ischemia in the Mongolian gerbil. J Basic Clin Physiol Pharmacol. 1990;1:207-220.
40. Mayevsky A, Rogatsky G. Mitochondrial function in vivo evaluated by NADH fluorescence: From animal models to human studies. Am J Physiol Cell Physiol. 2007;292:C615-C640.
41. Mayevsky A, Chance B. Intracellular oxidation-reduction state measured in situ by a multicannel fiber-optic surface fluorometer. Science. 1982;217:537-540.
42. Dirnagl U, Kaplan B, Jacewicz M, Pulsinelli W. Continuous measurement of cerebral cortical blood flow by laser-Doppler flowmetry in a rat stroke model. J CBF Metab. 1989;9:589-596.
43. Haberl RL, Heizer ML, Marmarou A, Ellis EF. Laser-Doppler assessment of brain microcirculation: effect of systemic alterations. Am J Physiol Heart Circ Physiol. 1989;256:H1247-1254.
44. Wadhwani KC, Rapoport SI, Shepherd AP, Oberg PA. Blood flow in the central and peripheral nervous systems. In: Shephrd AP, Oberg PA, eds. Laser Doppler Blood Flowmetry Vol 107. Boston: Kluwer Academic Pub; 1990:265-304.
45. Mayevsky A. Mitochondrial function and energy metabolism in cancer cells: past overview and future perspectives. Mitochondrion. 2009;9:165-179.
46. Meirovithz E, Sonn J, Mayevsky A. Effect of hyperbaric oxygenation on brain hemodynamics, hemoglobin oxygenation and mitochondrial NADH. Brain Res Rev. 2007;54(2):294-304.
47. Rampil IJ, Litt L, Mayevsky A. Correlated, simultaneous, multiple-wavelength optical monitoring in vivo of localized cerebrocortical NADH and brain microvessel hemoglobin oxygen saturation. J Clin Monit. 1992;8(3):216-225.
48. Crowe W, Mayevsky A, Mela L. Application of a solid membrane ion selective electrode to in vivo measurements. Am J Physiol. 1977;233:C56-C60.
49. Mayevsky A. Multiparameter monitoring of the awake brain under hyperbaric oxygenation. J Appl Physiol. 1983;54(3):740-748.
50. Mayevsky A. Biochemical and physiological activities of the brain as in vivo markers of brain pathology. In: Bernstein EF, Callow AD, Nicolaides AN, Shifrin EG, eds. Cerebral Revascularization. Med-Orion Pub.; 1993:51-69.
51. Mayevsky A, Doron A, Manor T, Meilin S, Salame K, Quaknine GE. Repetitive cortical spreading depression cycle development in the human brain: A multiparametric monitoring approach. J Cereb Blood Flow Metab 1995;15:534.
52. Meilin S, Rogatsky GG, Thom SR, Zarchin N, Guggenheimer-Furman E, Mayevsky A. Effects of carbon monoxide exposure on the brain may be mediated by nitric oxide. J Appl Physiol. 1996;81:1078-1083.
53. Rogatsky GG, Mayevsky A, Zarchin N, Doron A. Continuous multiparametric monitoring of brain activities following fluid-percussion injury in rats: Preliminary results. J Basic Clin Physiol Pharmacol. 1996;7:23-43.
54. Mayevsky A. Ischemia in the brain: The effects of carotid artery ligation and decapitation on the energy state of the awake and anesthetized rat. Brain Res. 1978;140:217-230.
55. Mayevsky A, Chance B. Repetitive patterns of metabolic changes during cortical spreading depression of the awake rat. Brain Res. 1974;65:529-533.
56. Mayevsky A, Zeuthen T, Chance B. Measurements of extracellular potassium, ECoG and pyridine nucleotide levels during cortical spreading depression in rats. Brain Res. 1974;76:347-349.
57. Mayevsky A, Chance B. Metabolic responses of the awake cerebral cortex to anoxia hypoxia spreading depression and epileptiform activity. Brain Res. 1975;98:149-165.
58. Rosenthal M, Somjen G. Spreading depression, sustained potential shifts, and metabolic activity of cerebral cortex of cats. J Neurophysiol. 1973;36:739-749.
59. Dora E, Zeuthen T. Brain metabolism and ion movements in the brain cortex of the rat during anoxia. In: Kessler M, ed. Ion and Enzyme Electrodes in Biology and Medicine. Baltimore: University.Park Press; 1976:294-298.
60. Mayevsky A, Zarchin N, Tannenbaum B. Brain responses to experimental oxygen deficiency in the Mongolian gerbil. Adv Exp Med Biol. 1984;180:191-202.
61. Vyskocil F, Kritz N, Bures J. Potassium-selective microelectrodes used for measuring the extracellular brain potassium during spreading depression and anoxic depolarization in rats. Brain Res. 1972;39(1):255-259.
62. Hansen AJ. Effect of anoxia on ion distribution in the brain. Physiol Rev. 1985;65:101-148.
63. Mayevsky A. Level of ischemia and brain functions in the Mongolian gerbil in vivo. Brain Res. 1990;524:1-9.
64. Mayevsky A, Friedli CM, Reivich M. Metabolic, ionic and electrical responses of the gerbil brain to ischemia. Am J Physiol. 1985;248:R99-R107.
65. Erecinska M, Silver IA. ATP and brain function. J Cereb Blood Flow Metab. 1989;9(1):2-19.
66. Heuser D, Guggenberger H. Ionic changes in brain ischaemia and alterations produced by drugs. Br J Anaesth. 1985;57(1):23-33.
67. Cohen S, Mayevsky A. Effects of nimodipine on the responses to cerebral ischemia in the Mongolian gerbil. Adv Exp Med Biol. 1989;248:429-438.
68. Dierking H, Tegtmeier E, Holler M, Peters TL. Effects of flunarizine, nimodipine, and diphenylhydantoine on K, Ca and DC in the flunarizine, nimodipine, and diphenylhydantoine on hypoxic cortex of the rat brain in vivo. J Cereb Blood Flow Metab. 1987;7:S 156.
69. Mori K, Iwayama K, Kawano T, Kaminogo M. DC potential and extracellular K+ and Ca2+ at critical levels of brain ischemia in cats. J Cereb Blood Flow Metab. 1978;7:s112.
70. Kato H, Nakano S, Kogure K. Repeated innocent ischemia to the brain can injure the selectively vulnerable neurons in the gerbil and the rat. J Cereb Blood Flow Metabol. 1989;9:S642.
71. Mayevsky A, Breuer Z. The Mongolian gerbil as a model for cerebral ischemia. In: Schurr A, Rigor BM, eds.: CRC Press; 1990:27-46.
2. Barcroft J. The Respiratory Function of Blood. Cambridge: Cambridge University Press; 1914.
3. Fink MP. Bench-to-bedside review: Cytopathic hypoxia. Critical Care (London, England). 2002;6:491-499.
4. Robertson CL, Soane L, Siegel ZT, Fiskum G. The potential role of mitochondria in pediatric traumatic brain injury. Developmental neuroscience. 2006;28:432-446.
5. Sullivan PG, Krishnamurthy S, Patel SP, Pandya JD, Rabchevsky AG. Temporal characterization of mitochondrial bioenergetics after spinal cord injury. J Neurotrauma. 2007;24:991-999.
6. Sims NR, Anderson MF. Mitochondrial contributions to tissue damage in stroke. Neurochem Internat. 2002;40:511-526.
7. Ying W. NAD+ and NADH in cellular functions and cell death. Front Biosci. 2006;11:3129-3148.
8. Ying W. NAD+ and NADH in brain functions, brain diseases and brain aging. Front Biosci. 2007;12:1863-1888.
9. Kann O, Kovacs R. Mitochondria and neuronal activity. Am J Physiol Cell Physiol. 2007;292(2):C641-C657.
10. Edeas M, Weissig V. Targeting mitochondria: Strategies, innovations and challenges The future of medicine will come through mitochondria. Mitochondrion. 2013;13(5):389-390.
11. Chance B, Cohen P, Jobsis F, Schoener B. Intracellular oxidation-reduction states in vivo. Science. 1962;137:499-508.
12. Chance B, Oshino N, Sugano T, Mayevsky A. Basic principles of tissue oxygen determination from mitochondrial signals. Oxygen Transport to Tissue, Adv Exp Med Biol. 1973;37A:277-292.
13. Lubbers DW. Optical sensors for clinical monitoring. Acta Anaesth Scand Suppl. 1995;39(104):37-54.
14. Chance B, Williams GR. Steady-state of reduced pyridine nucleotides in phosphorylating rat liver mitochondria. Am Soc Biol Chem. 1954;13. Abstract 633.
15. Chance B, Williams GR. Respiratory enzymes in oxidative phosphorylation (III- The steady state). J Biol Chem. 1955;217:409-427.
16. Chance B, Williams GR. Respiratory enzymes in oxidative phosphorylation (I- Kinetics of oxygen utilization). J Biol Chem. 1955;217:383-393.
17. Connelly CM, Chance B. Kinetics of reduced pyridine nucleotides in stimulated frog muscle and nerve. Am Physiol Soc. 1954;13(1):29-.
18. Chance B, Jobsis F. Changes in fluorescence in a frog sartorius muscle following a twitch. Nature. 1959;184:195-196.
19. Chance B, Cohen P, Jobsis F, Schoener B. Localized fluorometry of oxidation-reduction states of intracellular pyridine nucleotide in brain and kidney cortex of the anesthetized rat. Science. 1962;136:325.
20. Chance B, Legallias V, Schoener B. Metabolically linked changes in fluorescence emission spectra of cortex of rat brain, kidney and adrenal gland. Nature. 1962;195:1073-1075.
21. Chance B, Schoener B. Correlation of oxidation-reduction changes of intracellular reduced pyridine nucleotide and changes in electro-encephalogram of the rat in anoxia. Nature. 1962;195:956-958.
22. Chance B, Schoener B. Control of oxidation-reduction state of NADH in the liver of anesthetized rats. Symp Regul Enzyme Act Synth Norm Neoplast Tissues Proc. 1963:169-185.
23. Chance B, Schoener B, Fergusson JJ. In vivo induced oxidation by adrenocorticotrophic hormone of reduced pyridine nucleotide in the adrenal cortex of hypophysectomized rats. Nature. 1962;195:776-778.
24. Mayevsky A, Chance B. A new long-term method for the measurement of NADH fluorescence in intact rat brain with implanted cannula. In: Bicher HI, Bruley DF, eds. Vol 37A. New York: Plenum Press; 1973:239-244.
25. Mayevsky A. Brain NADH redox state monitored in vivo by fiber optic surface fluorometry. Brain Res Rev. 1984;7:49-68.
26. Vatov L, Kizner Z, Ruppin E, Meilin S, Manor T, Mayevsky A. Modeling brain energy metabolism and function: A multiparametric monitoring approach. Bull Math Biol. 2006;68:275-291.
27. Mayevsky A, Barbiro-Michaely E. Shedding light on mitochondrial function by real time monitoring of NADH fluorescence: I. Basic methodology and animal studies. J Clin Monit Comp. 2013;27:1-34.
28. Mayevsky A, Barbiro-Michaely E. Shedding light on mitochondrial function by real time monitoring of NADH fluorescence: II: Human studies. J Clin Monit Comp. 2013;27:125-145.
29. Rutkai I, Merdzo I, Wunnava SV, Curtin GT, Katakam PV, Busija DW. Cerebrovascular function and mitochondrial bioenergetics after ischemia-reperfusion in male rats. J Cereb Blood Flow Metab. 2019;39(6):1056-1068.
30. Liu F, Lu J, Manaenko A, Tang J, Hu Q. Mitochondria in Ischemic Stroke: New Insight and Implications. Aging Dis. 2018;9(5):924-937.
31. Yang JL, Mukda S, Chen SD. Diverse roles of mitochondria in ischemic stroke. Redox Biol. 2018;16:263-275.
32. Sperling JA, Sakamuri S, Albuck AL, et al. Measuring Respiration in Isolated Murine Brain Mitochondria: Implications for Mechanistic Stroke Studies. Neuromolecular Med. 2019;21(4):493-504.
33. Chen W, Huang J, Hu Y, Khoshnam SE, Sarkaki A. Mitochondrial Transfer as a Therapeutic Strategy Against Ischemic Stroke. Transl Stroke Res. 2020;11(6):1214-1228.
34. An H, Zhou B, Ji X. Mitochondrial quality control in acute ischemic stroke. J Cereb Blood Flow Metab. 2021;41(12):3157-3170.
35. Yang M, He Y, Deng S, et al. Mitochondrial Quality Control: A Pathophysiological Mechanism and Therapeutic Target for Stroke. Front Mol Neurosci. 2021;14:786099.
36. Tian H, Chen X, Liao J, et al. Mitochondrial quality control in stroke: From the mechanisms to therapeutic potentials. J Cell Mol Med. 2022;26(4):1000-1012.
37. Mayevsky A, Lebourdais S, Chance B. The interrelation between brain PO2 and NADH oxidation- reduction state in the gerbil. J Neurosci Res. 1980;5:173-182.
38. Friedli CM, Sclarsky DS, Mayevsky A. Multiprobe monitoring of ionic, metabolic, and electrical activities in the awake brain. Am J Physiol. 1982;243(3):R462-469.
39. Mayevsky A, Yoles E, Zarchin N, Kaushansky D. Brain vascular ionic and metabolic responses to ischemia in the Mongolian gerbil. J Basic Clin Physiol Pharmacol. 1990;1:207-220.
40. Mayevsky A, Rogatsky G. Mitochondrial function in vivo evaluated by NADH fluorescence: From animal models to human studies. Am J Physiol Cell Physiol. 2007;292:C615-C640.
41. Mayevsky A, Chance B. Intracellular oxidation-reduction state measured in situ by a multicannel fiber-optic surface fluorometer. Science. 1982;217:537-540.
42. Dirnagl U, Kaplan B, Jacewicz M, Pulsinelli W. Continuous measurement of cerebral cortical blood flow by laser-Doppler flowmetry in a rat stroke model. J CBF Metab. 1989;9:589-596.
43. Haberl RL, Heizer ML, Marmarou A, Ellis EF. Laser-Doppler assessment of brain microcirculation: effect of systemic alterations. Am J Physiol Heart Circ Physiol. 1989;256:H1247-1254.
44. Wadhwani KC, Rapoport SI, Shepherd AP, Oberg PA. Blood flow in the central and peripheral nervous systems. In: Shephrd AP, Oberg PA, eds. Laser Doppler Blood Flowmetry Vol 107. Boston: Kluwer Academic Pub; 1990:265-304.
45. Mayevsky A. Mitochondrial function and energy metabolism in cancer cells: past overview and future perspectives. Mitochondrion. 2009;9:165-179.
46. Meirovithz E, Sonn J, Mayevsky A. Effect of hyperbaric oxygenation on brain hemodynamics, hemoglobin oxygenation and mitochondrial NADH. Brain Res Rev. 2007;54(2):294-304.
47. Rampil IJ, Litt L, Mayevsky A. Correlated, simultaneous, multiple-wavelength optical monitoring in vivo of localized cerebrocortical NADH and brain microvessel hemoglobin oxygen saturation. J Clin Monit. 1992;8(3):216-225.
48. Crowe W, Mayevsky A, Mela L. Application of a solid membrane ion selective electrode to in vivo measurements. Am J Physiol. 1977;233:C56-C60.
49. Mayevsky A. Multiparameter monitoring of the awake brain under hyperbaric oxygenation. J Appl Physiol. 1983;54(3):740-748.
50. Mayevsky A. Biochemical and physiological activities of the brain as in vivo markers of brain pathology. In: Bernstein EF, Callow AD, Nicolaides AN, Shifrin EG, eds. Cerebral Revascularization. Med-Orion Pub.; 1993:51-69.
51. Mayevsky A, Doron A, Manor T, Meilin S, Salame K, Quaknine GE. Repetitive cortical spreading depression cycle development in the human brain: A multiparametric monitoring approach. J Cereb Blood Flow Metab 1995;15:534.
52. Meilin S, Rogatsky GG, Thom SR, Zarchin N, Guggenheimer-Furman E, Mayevsky A. Effects of carbon monoxide exposure on the brain may be mediated by nitric oxide. J Appl Physiol. 1996;81:1078-1083.
53. Rogatsky GG, Mayevsky A, Zarchin N, Doron A. Continuous multiparametric monitoring of brain activities following fluid-percussion injury in rats: Preliminary results. J Basic Clin Physiol Pharmacol. 1996;7:23-43.
54. Mayevsky A. Ischemia in the brain: The effects of carotid artery ligation and decapitation on the energy state of the awake and anesthetized rat. Brain Res. 1978;140:217-230.
55. Mayevsky A, Chance B. Repetitive patterns of metabolic changes during cortical spreading depression of the awake rat. Brain Res. 1974;65:529-533.
56. Mayevsky A, Zeuthen T, Chance B. Measurements of extracellular potassium, ECoG and pyridine nucleotide levels during cortical spreading depression in rats. Brain Res. 1974;76:347-349.
57. Mayevsky A, Chance B. Metabolic responses of the awake cerebral cortex to anoxia hypoxia spreading depression and epileptiform activity. Brain Res. 1975;98:149-165.
58. Rosenthal M, Somjen G. Spreading depression, sustained potential shifts, and metabolic activity of cerebral cortex of cats. J Neurophysiol. 1973;36:739-749.
59. Dora E, Zeuthen T. Brain metabolism and ion movements in the brain cortex of the rat during anoxia. In: Kessler M, ed. Ion and Enzyme Electrodes in Biology and Medicine. Baltimore: University.Park Press; 1976:294-298.
60. Mayevsky A, Zarchin N, Tannenbaum B. Brain responses to experimental oxygen deficiency in the Mongolian gerbil. Adv Exp Med Biol. 1984;180:191-202.
61. Vyskocil F, Kritz N, Bures J. Potassium-selective microelectrodes used for measuring the extracellular brain potassium during spreading depression and anoxic depolarization in rats. Brain Res. 1972;39(1):255-259.
62. Hansen AJ. Effect of anoxia on ion distribution in the brain. Physiol Rev. 1985;65:101-148.
63. Mayevsky A. Level of ischemia and brain functions in the Mongolian gerbil in vivo. Brain Res. 1990;524:1-9.
64. Mayevsky A, Friedli CM, Reivich M. Metabolic, ionic and electrical responses of the gerbil brain to ischemia. Am J Physiol. 1985;248:R99-R107.
65. Erecinska M, Silver IA. ATP and brain function. J Cereb Blood Flow Metab. 1989;9(1):2-19.
66. Heuser D, Guggenberger H. Ionic changes in brain ischaemia and alterations produced by drugs. Br J Anaesth. 1985;57(1):23-33.
67. Cohen S, Mayevsky A. Effects of nimodipine on the responses to cerebral ischemia in the Mongolian gerbil. Adv Exp Med Biol. 1989;248:429-438.
68. Dierking H, Tegtmeier E, Holler M, Peters TL. Effects of flunarizine, nimodipine, and diphenylhydantoine on K, Ca and DC in the flunarizine, nimodipine, and diphenylhydantoine on hypoxic cortex of the rat brain in vivo. J Cereb Blood Flow Metab. 1987;7:S 156.
69. Mori K, Iwayama K, Kawano T, Kaminogo M. DC potential and extracellular K+ and Ca2+ at critical levels of brain ischemia in cats. J Cereb Blood Flow Metab. 1978;7:s112.
70. Kato H, Nakano S, Kogure K. Repeated innocent ischemia to the brain can injure the selectively vulnerable neurons in the gerbil and the rat. J Cereb Blood Flow Metabol. 1989;9:S642.
71. Mayevsky A, Breuer Z. The Mongolian gerbil as a model for cerebral ischemia. In: Schurr A, Rigor BM, eds.: CRC Press; 1990:27-46.