Cortical NADH during pharmacological manipulations of the respiratory chain and spreading depression in vivo

Rex, André; Fink, F.; Fink, Heidrun

doi:10.1002/(sici)1097-4547(19990801)57:3<359::aid-jnr8>3.0.co;2-5

Cited by 32 publications

(34 citation statements)

References 38 publications

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“…Numerous reports confirmed that neuronal excitation in intact brain was accompanied by sustained oxidation of NADH [19,30,[34][35][36][37][38][39][40][41][42][43][44][45]. A close correlation was also observed between NADH oxidation and oxygen consumption in cat and rat neocortex [46,47].…”

Section: Redox Responses In Excited Brain Tissue In Vivomentioning

confidence: 78%

“…In the case of SD, hyperemia predominates while neurons are depolarized but this is usually followed by prolonged hypo-perfusion [72][73][74][75][76][77][78]. The late hypo-perfusion following SD can cause delayed reduction of NADH-NAD + [44]. In the cortex of anesthetized mice, the response varies among micro-domains, according to the distance from capillaries [52].…”

Section: Oxygen Availability -Resolving the Discrepancy Between In VImentioning

confidence: 99%

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Differences in O2 availability resolve the apparent discrepancies in metabolic intrinsic optical signals in vivo and in vitro

Turner

Foster

Galeffi

et al. 2007

Trends in Neurosciences

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Monitoring changes in the fluorescence of metabolic chromophores, reduced nicotinamide adenine dinucleotide and flavin adenine dinucleotide, and the absorption of cytochromes, is useful to study neuronal activation and mitochondrial metabolism in the brain. However, these optical signals evokedby stimulation, seizures and spreading depression in intact brain differ from those observed in vitro. The responses in vivo consist of a persistent oxidized state during neuronal activity followed by mild reduction during recovery. In vitro, however, brief oxidation is followed by prolonged and heightened reduction, even during persistent neuronal activation. In normally perfused, oxygenated and activated brain tissue in vivo, partial pressure of oxygen (P O2 ) levels often undergo a brief 'dip' that is always followed by an overshoot above baseline, due to increased blood flow (neuronal-vascular coupling). By contrast, in the absence of blood circulation, tissue P O2 in vitro decreases more markedly and recovers slowly to baseline without overshooting. Although oxygen is abundant in vivo, it is diffusion-limited in vitro. The disparities in mitochondrial and tissue oxygen availability account for the different redox responses. Changes in redox level of mitochondrial respiratory chain components can be monitored in live brain tissue by optical imagingChanges in fluorescence of metabolic cofactors [i.e. reduced nicotinamide adenine dinucleotide (NADH) ‡ and flavin adenine dinucleotide (FAD)] involved in energy processes, and in the absorption spectrum of cytochromes, provide a measure of their redox level. Mitochondrial energy metabolism is tightly coupled with neuronal activity, and changes in metabolic activity alter the redox level of these cofactors. Optical changes related to redox state have been used for many years to gauge the metabolic activity in brain and in other organs. Relating redox responses to electrical, mechanical or secretory processes has provided a rich source of data on the coupling of metabolic activity to their function. Such investigations in mammalian brain shed light on the mechanism of seizures, of spreading depression (SD) and of hypoxia and ischemia. Recently, however, a discrepancy has become apparent between the pattern of redox changes in intact, perfused brain 'in vivo' * , and isolated preparations of central neurons, tissue slices and slice cultures maintained 'in vitro' † in an organ bath. This essay aims at resolving the apparent discrepancy.Corresponding author: Turner, D.A. (dennis.turner@duke.edu). ‡ The term 'reduction' is used to denote shifts in redox state away from oxidation, not a decrease in a variable. * To avoid ambiguity, we use 'in vivo' to mean brain tissue in its anatomical location (in situ) and perfused by blood, usually studied in an anesthetized animal with functioning lungs, heart and autonomic reflexes. † 'In vitro' means isolated cells, tissue slices, cell cultures and organotypic slice cultures maintained in an oxygenated, saline-perfused organ bath. NI...

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Section: Redox Responses In Excited Brain Tissue In Vivomentioning

confidence: 78%

Section: Oxygen Availability -Resolving the Discrepancy Between In VImentioning

confidence: 99%

Differences in O2 availability resolve the apparent discrepancies in metabolic intrinsic optical signals in vivo and in vitro

Turner

Foster

Galeffi

et al. 2007

Trends in Neurosciences

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“…Renault and collaborators used a light guide fluorometer for monitoring heart in vivo (206,207). Rex and collaborators used another type of light guide fluorometer for the brain and other systems (202,208). Microlight guides were used for in vitro and in vivo studies (104,105,244).…”

Section: Monitoring Devices and Technological Aspectsmentioning

confidence: 99%

Mitochondrial function in vivo evaluated by NADH fluorescence: from animal models to human studies

Mayevsky¹,

Rogatsky²

2007

American Journal of Physiology-Cell Physiology

329

290

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Mayevsky A, Rogatsky GG. Mitochondrial function in vivo evaluated by NADH fluorescence: from animal models to human studies. Am J Physiol Cell Physiol 292: C615-C640, 2007. First published August 30, 2006; doi:10.1152/ajpcell.00249.2006.-Normal mitochondrial function is a critical factor in maintaining cellular homeostasis in various organs of the body. Due to the involvement of mitochondrial dysfunction in many pathological states, the real-time in vivo monitoring of the mitochondrial metabolic state is crucially important. This type of monitoring in animal models as well as in patients provides real-time data that can help interpret experimental results or optimize patient treatment. The goals of the present review are the following: 1) to provide an historical overview of NADH fluorescence monitoring and its physiological significance; 2) to present the solid scientific ground underlying NADH fluorescence measurements based on published materials; 3) to provide the reader with basic information on the methodologies used in the past and the current state of the art fluorometers; and 4) to clarify the various factors affecting monitored signals, including artifacts. The large numbers of publications by different groups testify to the valuable information gathered in various experimental conditions. The monitoring of NADH levels in the tissue provides the most important information on the metabolic state of the mitochondria in terms of energy production and intracellular oxygen levels. Although NADH signals are not calibrated in absolute units, their trend monitoring is important for the interpretation of physiological or pathological situations. To understand tissue function better, the multiparametric approach has been developed where NADH serves as the key parameter. The development of new light sources in UV and visible spectra has led to the development of small compact units applicable in clinical conditions for better diagnosis of patients.real-time tissue viability; tissue spectroscopy; patient monitoring UNDERSTANDING THE MITOCHONDRIAL function has been a challenge for many investigators, including cytologists, biochemists, and physiologists, since its discovery more than 120 years ago. In addition to many books regarding the mitochondria, Ernster and Schatz (79) reviewed the history of mitochondrial structure and function studies. In the past two decades, several studies have reported mitochondrial involvement in pathological processes such as stroke (225) or cytoprotection (77). Most of the information on the mitochondrial function has been accumulated from in vitro studies. A relatively small portion of published papers dealt with the monitoring of mitochondrial function in vivo and in real time. Presently, examination of the involvement of the mitochondrial function in many pathological states, such as sepsis, requires monitoring of patients treated in intensive care units. Unfortunately, real-time monitoring of the mitochondrial function in patients has rarely been performed. The current study pres...

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“…The hypoxic spreading depression like depolarization results in the rapid loss of transmembrane ion gradients. Subsequent normalization requires oxidative energy (Hansen and Lauritzen, 1984;Lipton, 1999) however in hypoxic brain tissue mitochondrial enzymes become reduced (Rosenthal and Somjen, 1973;Mayevsky and Chance, 1974;Rex et al, 1999). Fast-spiking interneurons, the pillars of gamma oscillations might be a critical target of alterations in oxygen tension and mitochondrial function (Ackermann et al, 1984;Fuchs et al, 2007).…”

Section: Hfd and DC Shift During Hippocampal Ischemiamentioning

confidence: 99%

Changes in Hippocampal Neuronal Activity During and After Unilateral Selective Hippocampal IschemiaIn Vivo

Barth¹,

Módy²

2011

J. Neurosci.

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The hippocampal formation is one of the brain regions most sensitive to ischemic damage. However, there are no studies about changes in hippocampal neuronal activity during and after a selective unilateral hippocampal ischemia. We developed a novel unilateral cerebrovascular ischemia model in mice that selectively shuts down blood supply to the ipsilateral hippocampal formation. Using a modified version of the photothrombotic method, we stereotaxically targeted the initial ascending part of the longitudinal hippocampal artery in urethane anesthetized and rose bengal-injected mice. To block blood flow in the targeted artery, we photoactivated the rose bengal by illuminating the longitudinal hippocampal artery through an optical fiber inserted into the brain. In vivo field potential recordings in the CA1 region of the hippocampus before, during and after the induction of ischemia demonstrated a high-frequency discharge (HFD) reaching frequencies of Ͼ300 Hz and lasting 7-24 s during the illumination consistent with a massive synchronous neuronal activity. The HFD was invariably followed by a DC voltage shift and a decreased activity at both low (30 -57 Hz)-and high (63-119 Hz)-gamma frequencies. This decrease in gamma activity lasted for the entire duration of the recordings (ϳ160 min) following ischemia. The contralateral hippocampus displayed HFDs but with different frequency spectra and without DC voltage shifts or long-lasting decreases in gamma oscillations. Our findings reveal for the first time the acute effects of unilateral hippocampal ischemia on ensemble hippocampal neuronal activities.

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Cortical NADH during pharmacological manipulations of the respiratory chain and spreading depression in vivo

Cited by 32 publications

References 38 publications

Differences in O2 availability resolve the apparent discrepancies in metabolic intrinsic optical signals in vivo and in vitro

Differences in O2 availability resolve the apparent discrepancies in metabolic intrinsic optical signals in vivo and in vitro

Mitochondrial function in vivo evaluated by NADH fluorescence: from animal models to human studies

Changes in Hippocampal Neuronal Activity During and After Unilateral Selective Hippocampal IschemiaIn Vivo

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