Papers by Avraham Mayevsky
Mitochondrial Function In Vivo Evaluated by NADH Fluorescence, 2015
In the early days, NADH was measured using the absorption properties of the molecule. The discove... more In the early days, NADH was measured using the absorption properties of the molecule. The discovery of the fluorescence emitted from the reduced form of NAD+ opened up new options to study mitochondria function under in vitro and in vivo conditions. The effects of various perturbations on the redox state of NADH were tested using different preparations at all organization levels, including NADH in solution, isolated mitochondria, cells, tissue slices, and up to in vivo monitoring of various organs of animals. Very small differences in NADH spectra were found between the various levels of biological organization. Significant correlation between NADH fluorescence measured in vivo and in biochemical assay was found. All those issues are described in this chapter.
Advances in Experimental Medicine and Biology, 1983
The normal functioning brain requires a continuous supply of blood in order to obtain glucose as ... more The normal functioning brain requires a continuous supply of blood in order to obtain glucose as well as oxygen. Any change in the oxygenation of the tissue will result in an impairment of the normal function. Most of the oxygen taken up by the brain is consumed by the mitochondria in order to supply the large amount of ATP needed. A major part of the ATP is used by the ATPase system in order to keep the neurons in the polarized state. Figure 1 shows in a schematic way the interrelation between the energy production system and the pumping activity going on in the membranes. In order to understand the connection between various events occurring in the brain in vivo, one has to measure as many parameters as possible from the same site.
Springer eBooks, 2015
To monitor NADH in various organs in vivo, it is very critical and important to prepare the anima... more To monitor NADH in various organs in vivo, it is very critical and important to prepare the animal model according to a standard protocol. The various techniques developed to create optimal contact between the optical probes and the tested organ are presented for the brain, spinal cord, heart, and visceral organs such as kidney and liver. The various factors affecting NADH fluorescence in vivo are described in detail in this chapter.
Medical research archives, 2023
More than 50% of total energy consumed by the brain is utilized by active transport processes whi... more 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 Ca 2+ 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 + , Ca 2+ , 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.
PubMed, 1977
Using a time-sharing fluorometer-reflectometer, pyridine nucleotide (NADH) and flavoprotein (Fp) ... more Using a time-sharing fluorometer-reflectometer, pyridine nucleotide (NADH) and flavoprotein (Fp) fluorescence, as well as reflected light at the excitation wavelength, were measured and correlated with the electrical activity of an awake cerebral cortex. Exposure of the rat to a nitrogen atmosphere (anoxia) led to an increase in signals representing the reduction of pyridine nucleotides and flavins, with very similar kinetics. Inducement of partial ischemia by bilateral carotid artery ligation led to an increase in NADH, accompanied by a very small effect on the electrical activity (ECoG). In most animals, 2-3 h after ligation, the ECoG became flat or depressed. Exposure of this ischemic cerebral cortex to KC1 solution caused depression of the electrical activity without metabolic response probably due to the limitation of oxygen supply. The metabolic state of an awake cerebral cortex was identified by exposing the brain to various levels of oxygen, epileptoform activity, spreading depression, hyperbaric pressure of oxygen and an uncoupler. From our results we conclude that the awake cerebral cortex is close to the resting state, state 4, rather than to the active state, state 3.
Springer eBooks, 2015
In the previous chapters, it was shown that monitoring of mitochondrial NADH is critical in under... more In the previous chapters, it was shown that monitoring of mitochondrial NADH is critical in understanding tissue oxygen balance. Nevertheless, because of the complexity of the physiological and biochemical processes, it is unavoidable and necessary to monitor as many parameters as possible at the tissue level together with mitochondrial NADH. During the past 40 years, we adopted this concept, and various techniques were developed and applied to different models of experimental animals exposed to many types of perturbations. The development of the technology included various sensors or probes that provide information on energy supply and demand in the tissue as described in this chapter. The various probes were organized in a compact multi-probe assembly that was located on the surface of the tissue without any visible damage. The various systems that were developed are presented in chronological order.
Neurological Research, 1981
AbstractChanges in the oxidation-reduction state of NADH were measured by surface fluorometry, us... more AbstractChanges in the oxidation-reduction state of NADH were measured by surface fluorometry, using quartz fiber optics, of an isolated rat brain perfused with an “artificial blood” (emulsified perfluorochemical) which avoids the optical interference caused by hemoglobin. The changes in fluorescence and electrical activity of the perfused brain in response to anoxia were about the same, qualitatively and quantitatively, as in the brain of the intact rat.
Medical research archives, 2023
Objectives: The discovery of cortical spreading depression 80 years ago by Leão was intimately co... more Objectives: The discovery of cortical spreading depression 80 years ago by Leão was intimately connected to epilepsy research. In our studies we found that monitoring of brain hemodynamics, metabolic ionic and electrical activities are very similar in the two pathophysiological events. Here we are presenting the coupling between epilepsy and cortical spreading depression while monitoring of mitochondrial nicotinamide adenine dinucleotide-NADH together with other physiological parameters in real time in vivo. Methods: Rats and Mongolian gerbils were used in three models of induction of epilepsy, namely injection of pentylenetetrazol-metrazol, exposure of the rats to hyperbaric oxygenation in a pressure chamber and using a strain of gerbils that are developing seizures spontaneously. We monitored brain oxygen levels, mitochondrial NADH, extracellular potassium levels, Direct Current-DC steady potential and electroencephalography-EEG in the very slightly anesthetized animals. Results: The results could be summarized as follows: 1. In almost all animal tested cortical spreading depression was developed and recorded after 1-3 minutes of seizures activity. 2. Mitochondrial NADH redox state was more oxidized during the two events. 3. The oxidation of NADH during the Cortical Spreading Depression-CSD was 3-4 times relative to the seizure's interval. 4. The increase in extracellular potassium levels was also 3-4 times higher during the CSD event. Significance: Under the two recorded events a clear correlation between the process of oxygen (energy) demand or consumption and oxygen (energy) supply was found. The results suggest that the accumulation of extracellular potassium during the epileptic activity is probably the trigger for the development of CSD in the 3 model used.
Journal of Biosensors and Bioelectronics, Oct 5, 2016
Journal of World Mitochondria Society, Apr 13, 2016
Mitochondrion, Jun 1, 2009
This article appeared in a journal published by Elsevier. The attached copy is furnished to the a... more This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit: http://www.elsevier.com/copyright
American Journal of Physiology-regulatory Integrative and Comparative Physiology, Sep 1, 1982
A new approach for studying brain metabolic, ionic, and electrical activities in the awake animal... more A new approach for studying brain metabolic, ionic, and electrical activities in the awake animal is described. We developed a multiprobe assembly holding electrodes for extracellular K+, pH, DC potential, electrocorticogram, and temperature as well as a light guide for monitoring intramitochondrial NADH oxidation-reduction state. The assembly was designed so that because of the type of electrodes used and the protection system around them, the same system could be used in many experiments. The results presented here are typical and show the potential use of the multiprobe approach for studying the effects of hypoxia, anoxia, spreading depression, and ischemia on the awake brain. From the results obtained the following conclusions can be drawn. 1) The DC correction for the K+ and H+ measurements is necessary, although it was not as good for the H+ as for the K+ signals. 2) During ischemia (complete or partial) a clear acidification of the brain was found in correlation with the decrease in oxygen availability as evaluated by the NADH fluorescence signal. 3) During brain activation (induced by spreading depression) extracellular K+ was elevated and then actively pumped back into the cells. The NADH showed an oxidation response, and the pH response started with an alkalinization followed by a short acidification.
Springer eBooks, 2015
The technology for the monitoring of NADH developed for animal studies was applied to monitor pat... more The technology for the monitoring of NADH developed for animal studies was applied to monitor patients who underwent various surgical procedures. The brain was the main organ monitored in neurosurgical patients who underwent vascular procedures or were treated in the ICU. Other organs, such as the muscle, kidney, or urethral wall, were monitored as well. Special devices and optical probes were developed and used in the early stage and were approved for use by the Institutional Review Board of the hospitals. In the last few years our devices were cleared by the FDA. Typical results of the main reports are presented in this chapter.
American journal of biomedical science & research, Feb 10, 2020
This work is licensed under Creative Commons Attribution 4.0 License AJBSR.MS.ID.001136.
Springer eBooks, 2015
This is the largest chapter in the book, covering the responses of NADH to various experimental p... more This is the largest chapter in the book, covering the responses of NADH to various experimental perturbations used in animal studies. It covers various changes in oxygen (low and high), CO2, and CO. The effects of an increase in oxygen consumption on NADH are presented. Epileptic seizures and cortical spreading depression (CSD) in the brain as well as in other organs such as the heart and skeletal muscle are included. The effects of various drugs on NADH fluorescence were tested in the brain as well as in other organs. Other effects such as age of the animal are also presented in this chapter.
Neuroscience Letters, Nov 1, 1997
S35 frequency-dependent inhibition (FDI), a reflection of one aspect of this circuit, is reduced ... more S35 frequency-dependent inhibition (FDI), a reflection of one aspect of this circuit, is reduced following HFS. Here we examined whether this type of plasticity is affected by aging. Young (up to 12 months) and old (> 18 months) rats were prepared for acute recording of field potentials in the dentate gyrus. FDI was measured before and 45 min after HFS. There was no difference in the magnitude of LTP but only in the young rats was a significant reduction in FDI obtained. The results indicate that this type of local circuit plasticity is compromised in aging.
Springer eBooks, 1978
The interrelations between convulsive activity, and CO2 concentration under hyperbaric oxygen con... more The interrelations between convulsive activity, and CO2 concentration under hyperbaric oxygen conditions were investigated by few investigators. It was shown in mice (Marshall and Lambertsen, 1961) and in cats (Taylor, 1949) that small elevation of CO2 under HPO, potentiated the toxicity phenomenon while higher levels of CO2 inhibited convulsions. Other investigators (Levy and Richards, 1962) came to the conclusion that addition of CO2 to the HPO chamber provided the animal with protection against toxicity. In our previous communication (Mayevsky et al., 1974) we found that 1.5% CO2 in oxygen potentiates the toxicity under pressure of 6 ATA. In order to understand the effects of CO2 on the response of the brain to HPO we measured the effects of various concentrations of CO2 on the electrical activity as well as the metabolic activity of the awake brain.
CSB, 2010
Real-time multiparametric evaluation of tissue pathophysiological conditions is of great value in... more Real-time multiparametric evaluation of tissue pathophysiological conditions is of great value in animal experiments and for clinic applications,and is receiving more and more attention by researchers in life sciences and medicine.It is well known that the real-time monitoring of pathophysiological conditions in patients is required during surgical procedures and in intensive care units(ICUs).Whether a critical condition such as ischemia and hypoxia can be detected in vital organs,such as heart and brain,is directly related to patient survival.Early detection of microcirculatory disturbances in non-vital organs will also help to increase the success rate of surgeries such as organ transplantation,and decrease the incidence of post-operative complications.Conventional parameters,such as blood pressure,electrocardiogram and pulse,which are monitored in clinics,play important roles in the real-time evaluation of vital signs;however,they do not provide enough information to expose early changes in local tissue pathophysiological conditions at the molecular level.NADH is an intrinsic autofluorescent molecule involved in the redox reactions of the mitochondrial respiratory chain and serves as a sensitive marker,reflecting metabolic states and cell vitality.This paper introduces in vivo techniques to monitor the cellular metabolic states based on NADH autofluorescence.This method,combined with synchronous parallel monitoring of multiple parameters such as microcirculatory blood flow and hemoglobin oxygenation,will not only be useful in studies of pathophysiological mechanisms and evaluation of drug effects in vivo,but could also be clinically applied in surgeries and ICUs to provide real-time dynamic information of vital signs.At present,the technique of monitoring one-dimensional NADH fluorescent signals is well developed,and has been applied from in vitro experiments to living cells,animals,and in clinical studies.The two-dimensional imaging technique has been previously used in vivo.However,three-dimensional imaging has only been successful in frozen tissue slices due to the limited penetration of NADH.There are some large challenges that need to be addressed in the future,such as how to overcome the bottleneck of limited light penetration caused by high scattering in biological tissues;and how to maximally reduce environmental interference of fluorescent signals.Once these problems have been overcome,it should be possible to achieve real-time multiparametric monitoring of tissue pathophysiological conditions at a molecular level.
Advances in experimental medicine and biology, 1997
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Papers by Avraham Mayevsky