Papers by Avraham Mayevsky
Medical Research Archives
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: ...
Advances in Experimental Medicine and Biology, 1973
The method developed by Chance et al. (1) which measures the oxidation-reduction state of NADH in... more The method developed by Chance et al. (1) which measures the oxidation-reduction state of NADH in vivo by surface fluorometry is in use in many laboratories. In all cases, acute preparations are used.
Journal of Applied Physiology, 1980
Hyperbaric oxygen toxicity (HPO), under various environmental and physiological conditions, was i... more Hyperbaric oxygen toxicity (HPO), under various environmental and physiological conditions, was identified by measuring the electrical, hemodynamic, and metabolic activity of the awake brain in rats. The electrical activity was evaluated by the electrocorticogram; the hemodynamic and metabolic activity were measured by use of the surface fluorometry/reflectometry technique. The oxidation-reduction state of NADH (metabolic activity) was measured by using the quartz fiber-optic system to excite the tissue and transmit the fluorescence-emitted light from the brain. The hemodynamic responses were evaluated from the reflectance signal. In three sets of experiments we tested the effects of pressure level, age, and protection agents (pentobarbital and diazepam) on the various parameters measured from the brain. The results can be summarized as follows. 1) The effect of the pressure level of the toxicity process is significant; the higher the pressure, the greater the toxicity. 2) The 60-ps...
Journal of Applied Physiology, 1983
American Journal of Physiology-Cell Physiology, 1977
A solid membrane electrode containing a highly selective ion-complexing agent immobilized in a po... more A solid membrane electrode containing a highly selective ion-complexing agent immobilized in a polymer membrane is applied to measurements in vivo from the surface of an organ. For the measurements reported here, an ion-complexing agent selective for potassium is incorporated in a silicone rubber membrane and applied to measure ion changes in the brain. Comparison is made to the measurements recorded with an ion-selective microelectrode in the cortical tissue. The surface electrode compares favorably with the microelectrode in terms of amplitude of response and response time for the changes seen in the phenomenon of cortical spreading depression of Leao. The methods reported here are amenable to a selection of ion measurements by incorporation of a suitable ion exchanger in a polymer membrane. Extracellular ion activity is monitored in the anesthetized animal by holding the electrode in a balanced suspension which provides a light, flexible contact to the organ of interest. In the u...
Neurological Research, 1980
Neurological Research, 1991
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.
Neurological Research, 1980
The effects of hyperbaric oxygenation (HPO) on mitochondrial activity, NADH oxidation-reduction s... more The effects of hyperbaric oxygenation (HPO) on mitochondrial activity, NADH oxidation-reduction state, and electrical activity were studied in the unanesthetized rat brain. Mitochondrial activity was measured in vitro after isolation of the mitochondria from brains exposed to HPO in mitochondria from brains exposed to HPO in vivo for various time intervals. The results showed that exposure of the brain to HPO in vivo decreased state 3 respiration of the mitochondria within 5-10 min of exposure. The level of respiration remained low until the final step of exposure. Despite this low respiration rate in vitro, the brain from which the mitochondria were isolated showed an oxidized state that, in comparison to the normoxic level of NADH, suggested a higher rate of respiration had occurred as a response to the convulsion appearing in vivo.
Neurological Research, 1980
The unanesthetized gerbil model was used to study the interrelation between metabolic, electrical... more The unanesthetized gerbil model was used to study the interrelation between metabolic, electrical and ionic activities in the brain. A combined K+DC surface electrode with a fiber optic light guide was implanted above the parietal cortex and cemented to the skull. The subjects were exposed to various pathological and physiological conditions such as anoxia, hypoxia, spreading cortical depression, and ischemia. During anoxia a leakage of cellular K+e was detected simultaneously with an increased level of NADH. The recovery phase in a few animals was followed by a spreading depression phenomenon. Exposing the brain to spreading depression led to a typical oxidation cycle of NADH, and the shape of this cycle was affected by hypoxia. Unilateral carotid artery ligation induced localized ischemia that affected cellular and K+e responses to spreading depression. Bilateral carotid artery occlusion increased NADH concentration to its maximum level; as a result, K+e also accumulated. Complete restoration of NADH and K+e to normoxic levels occurred after a few minutes, depending on the duration of the occlusion.
Neurological Research, 1981
The kinetics of extracellular K+ activity was compared to the availability of energy in the corte... more The kinetics of extracellular K+ activity was compared to the availability of energy in the cortex of rats and gerbils exposed to anoxia, hypoxia, spreading depression, and ischemia. A combined K+/DC surface electrode was used alone or together with a fiber optic light guide in various experiments. All experiments were done on slightly anesthetized animals that were practically awake. The results can be summarized in the following conclusions: (1) Under conditions such as hypoxia or ischemia, K+0 showed a two-phase efflux kinetics, and a transition or critical point was reached where the response proceeds at a higher rate. This critical point was in the range of 10-16 mEq/1 potassium. (2) Availability of oxygen is necessary but not sufficient for a full rate of recovery from a long-term oxygen-deprivation insult. (3) There is an energy debt or energy-transduction bottleneck formed during a prolonged O2 insufficiency. This debt is reversed slowly during the recovery phase even when full restitution of O2 supply and blood flow has occurred.
Neurological Research, 1991
A new in vivo model for studying brain metabolic and haemodynamic oscillatory phenomena during is... more A new in vivo model for studying brain metabolic and haemodynamic oscillatory phenomena during ischaemia is described. In this model acute or chronic occlusion of one or two carotid arteries in the rat is performed. Due to the partial ischaemia developed, oscillations in the level of intramitochondrial pyridine nucleotides (NADH) as well as flavoproteins (Fp) were recorded from the brain by monitoring the fluorescence of these respiratory chain components. The two fluorescent signals (NADH and Fp) were measured by using the time sharing or DC fluorometer/reflectometer. The changes in the reflected light at the excitation wavelengths (366 and 450 nm) were recorded simultaneously. Bilateral carotid artery occlusion induced immediate oscillations (6-9 waves per min) in the mitochondrial redox state as well as in tissue blood volume in both hemispheres. To verify the accuracy of the NADH monitoring system, including the correction technique for haemodynamic and other artifacts, we used the intracarotid artery saline bolus injection approach. The results could be summarized as follows: (1) unilateral carotid artery occlusion resulted in delayed development of oscillations, particularly in the ipsilateral hemisphere; (2) the oscillation phenomenon was reversible if recirculation restarted within 5 min. Occlusion for more than 30 min resulted in irreversible oscillations; (3) the oscillation appearances and intensities were affected by various physiological conditions. Vasoconstriction, induced by hyperoxia, stimulated the oscillations while vasodilation, induced by hypercapnia, depressed them. Anoxia, hypoxia and spreading depression (SD) abolished the oscillations. Glucose injection was not effective.(ABSTRACT TRUNCATED AT 250 WORDS)
Frontiers of Biological Energetics, 1978
Advances in Experimental Medicine and Biology, 1973
The importance of measuring intracellular oxygen concentrations in tissues has, over the years, e... more The importance of measuring intracellular oxygen concentrations in tissues has, over the years, emerged as a basic parameter in the physiology and biochemistry of living tissues. The credibility of oxyhemoglobin determinations, even as refined A/V differences, is taxed especially in cases where inhomogeneous tissues with variable oxygen demands and oxygen supply are served. The formation of lactic acid in the venous blood is often used as a criterion of anoxia, but it also lacks credibility where inhomogeneous circulatory pathways are served and in addition, is questionable from the standpoint of whether the appearance of excess lactate is an unequivocal criterion of oxygen insufficiency. To indicate my empathy with polarographic techniques as they have been developed at the Johnson Foundation, I wish to recall the pioneering works of Bronk(1) Brink (2), Davies and Remond (3) that stand as landmarks in the exploration of tissue oxygen tension by microelectrode methods. I served my apprenticeship with them.
Advances in Experimental Medicine and Biology, 1983
There are few non-destructive non-invasive approaches to the study of cortical oxidative metaboli... more There are few non-destructive non-invasive approaches to the study of cortical oxidative metabolism. Nevertheless, the great necessity for the development and application of such approaches arises from the inadequacy of cell and brain slice models on the one hand and the need for interpretive monitoring of brain metabolism in humans, or if possible, under non-operative conditions. Two techniques can be used to study metabolism of the brain without the necessity of an operation, 31P NMR which is totally non-invasive and positron emission tomography which requries injection and delivery of the radio isotope. Neither of these methods affords an adequately sharp localization to provide better than regional localization (lam) under current conditions of development and application, on the other hand, when the subject is sacrificed and autoradiography of tritium labelled deoxyglucose is employed, a high degree of metabolic resolution can be obtained albeit the method averages events over times as long as 45 minutes. The need for a non-destructive continuous read out method for brain metabolism providing a high degree of localization, both spacially and within appropriate metabolic compartments is obtained with the fluorescence of mitochondrial pigments, NADH or flavoprotein. Furthermore, this method is applicable as well to frozen tissue surfaces affording high resolution 3D spacial resolution. The discovery that mitochondrial NADH is fluorescent and that the fluorescence is enhanced 15 or more times over that of the pigment in solution afforded a unique “look” at metabolic events in the matrix base of mitochondria; the NADPH therein was found not to respond to variations of electron transport in the respiratory chain (1–3). Furthermore, comparisons of changes of NADH fluorescence could be well correlated with actual tissue assays of NADH in heart and liver (4,5).
Time-Resolved Spectroscopy and Imaging of Tissues, 1991
Monitoring of brain functions during neurosurgical conditions have been made by various groups of... more Monitoring of brain functions during neurosurgical conditions have been made by various groups of investigators. Attempts were made to monitor EEG or evoked potentials, cerebral blood flow, mitochondrial redox state during various neurosurgical procedures. In order to monitor various functions of the brain we have developed a new multiprobe (MPA) assembly, based on fiber optic probes and ion selective electrodes, enabling the assessment of relative CBF, mitochondrial redox state (NADH fluorescence) and ion homeostasis in real-time, intraoperatively. The base features of the multiprobe assembly were described previously (A. Mayevsky, J. Appl. Physiol. 54, 740-748, 1983). The multiprobe holder (made of Delarin) contained a bundle of fibers transmitting light to and from the brain as well as 3 ion selective electrodes (K+%/, Ca(superscript 2+, Na+) combined with DC steady potential electrodes (Ag/AgCl). The common part of the light guide contained 2 groups of fibers. For the Laser Doppler flowmetry one input fiber and two output fibers were glued in a triangular shape and connected to the standard commercial plug of the Laser Doppler flowmeter. For the monitoring of NADH redox state 10 excitation and 10 emission fibers were randomly mixed between and around the fibers used for the Laser Doppler flowmetry. This configuration of the fibers enabled us to monitor CBF and NADH redox state from about the same tissue volume. The ion selective electrodes were connected to an Ag/AgCl electrode holders and the entire MPA was protected by a Plexiglass sleeve. Animal experiments were used for the verification of the methods and recording of typical responses to various pathological situations. The entire multiprobe assembly was sterilized by the standard gas sterilization routine and was checked for electrodes integrity and calibration inside the operation room 24 hours later. The MPA was located on the exposed human cortex using a micromanipulator and data collection started immediately after, using a micro computer based data acquisition system. After recording of baseline levels of CBF, NADH redox state and extracellular ion levels, the responses to CBF decrease (occlusions of a blood vessel) were recorded followed by the recovery period. A significant correlation between the CBF and NADH redox state changes was recorded. This approach enabled us to correlate this change in energy supply, to those of extracellular ion concentration. The preliminary results obtained suggest that the usage of the MPA in the operating room may have a significant contribution to the neurosurgeon as a routine diagnostic tool. It seems to us that a simplified MPA which will enable to monitor only the relative CBF, NADH redox state as well as extracellular K+ is more appropriate for future usage.
Mitochondrial Function In Vivo Evaluated by NADH Fluorescence, 2015
Monitoring of NADH fluorescence, as an indicator for mitochondrial function, started by using iso... more Monitoring of NADH fluorescence, as an indicator for mitochondrial function, started by using isolated mitochondria from various organs. This in vitro monitoring approach was applied, later on, to various organs monitored in the intact animal in vivo. In this chapter, a detailed description is given regarding the use of the technology in various organs as well as in different animal models. Typical results obtained in various animal models are presented in an analog record. Each table contains the lsit of references published on one organ, subcategorized by the various animals used.
Mitochondrial Function In Vivo Evaluated by NADH Fluorescence, 2015
The functional capacity of any tissue is dependent on its ability to perform work. It is possible... more The functional capacity of any tissue is dependent on its ability to perform work. It is possible to assess this ability through the knowledge of changes in the oxygen balance, that is, the ratio of oxygen supply to oxygen demand by the tissue. Monitoring of mitochondrial NADH redox state is sensitive to changes in oxygen supply as well as oxygen balance. The addition of microcirculatory blood flow and hemoglobin oxygenation to the real-time monitoring of NADH has significant value in understanding the development of tissue pathophysiology. The same approach could be applied as a practical clinical tool or device in patient monitoring.
Microcirculation in Circulatory Disorders, 1988
The Mongolian gerbil (Meriones unguiculatus) is a very useful animal model for studying brain res... more The Mongolian gerbil (Meriones unguiculatus) is a very useful animal model for studying brain responses to partial or complete ischemia [1–5]. Various aspects of brain functions and responses have been studied in this model exposed to ischemic conditions. When cerebral blood flow diminished due to the ischemia [6], inhibition of the Na+K+ ATPase occurred and, as a result, extracellular K+ level increased [7, 8]. In 1978, we described the effects of ischemia on the metabolic activity in the gerbil brain using the surface fluorometry technique to monitor reduced nicotinamide adenine dinucleotide (NADH) redox state [9]. In ischemia, we described a new phenomenon defined as secondary reflectance increase (SRI), [10]; this event is associated with ionic homeostasis disturbances which occur under energy deprivation conditions. To study this microcirculatory phenomenon under ischemia, the multiparametric monitoring approach [8] was used. Metabolic activity was measured by monitoring tissue surface O2 tension by a surface electrode. Intramitochondrial NADH redox state was evaluated by the surface fluorometry reflectometry technique described in detail previously [11]. The reflected light at the excitation wavelength (336 nm) measured simultaneously with the fluorescence light (450 nm) was used to correct the fluorescence signal for hemodynamic artifacts. This signal is largely dependent upon blood volume at the measurement site. Extracellular K+ activity was measured by a surface valinomycine electrode located in the multiprobe assembly.
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Papers by Avraham Mayevsky