Oxygen insufficiency during hypoxic hypoxia in rat brain cortex

LaManna, Joseph Charles; Light, Andrew I.; Peretsman, Samuel J.; Rosenthal, Myron

doi:10.1016/0006-8993(84)91238-1

Cited by 37 publications

(22 citation statements)

References 25 publications

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“…An earlier study showed that the initial member of the mitochondrial respiratory chain, NAD, also became transiently more oxidized in response to neuronal activation during normoxia, but that NAD also became reduced during activation under hyp oxic conditions (LaManna et al, 1984). These data contrast with data by Dora et al (1984) that NAD became reduced during neuronal activation in nor moxia.…”

Section: Discussionmentioning

confidence: 88%

“…The consistent presence of an oxidation peak at 605 nm demonstrated that oxida tion of cytochrome a,a3 can be recorded in intact, normoxic brain, despite the presence of hemo globin in the optical field. Since NAD and cy tochrome a,a3 redox activities were altered by hyp oxia in a similar manner (LaManna et al, 1984), then differences observed by Dora et al (1984) re main unexplained but suggest complications due ei ther to hypoxia or to light scattering.…”

Section: Discussionmentioning

confidence: 95%

“…Since previous studies (LaManna et aI., 1984) indicated that there are advantages in studying oxygen sufficiency under "active" rather than "resting" conditions in brain, emphasis was upon the recording of re sponses of mitochondrial redox carriers and K + 0 to electro cortical stimulation. Some of these findings have been presented in preliminary form (Milito et aI., 1986).…”

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confidence: 99%

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Potassium Ion Homeostasis and Mitochondrial Redox Activity in Brain: Relative Changes as Indicators of Hypoxia

Milito

Raffin

Rosenthal

et al. 1988

J Cereb Blood Flow Metab

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Summary: This study was directed at relating ion trans port and mitochondrial redox activity during hypoxia, as a step toward definition of brain oxygen sufficiency. To accomplish this, extracellular potassium ion activity (K+o) was recorded by ion-selective microelectrodes while reduction/oxidation (redox) ratios of cytochrome oxidase (cytochrome a,a3) were monitored by reflection spectrophotometry in cerebral cortex of rats anesthetized with pentobarbital. In normoxia, neuronal activation by direct cortical stimulation produced transient oxidation of cytochrome a,a3 and elevation of K +0. Moderate hyp oxia (Pao2 above 50 mm Hg) resulted in reduction of cy tochrome a,a3 but only slight elevation of K +0. At this level of hypoxia, cytochrome a,a3 continued to respond to neuronal activation with transient shifts toward oxida tion and rates of K + 0 reaccumulation were unchanged from control. When Pao2 was further decreased below a critical threshold, stimulus-provoked oxidative responsesMaintenance of brain oxygenation is critical for normal function, ion homeostasis, and cell survival. Early consequences of brain anoxia include rapid reduction of the mitochondrial electron carriers, depression of synaptic transmission, loss of EEG activity and consciousness, and a slow increase in extracellular potassium ion activity (K +0). Subse quent to these changes, a K + 0 threshold is reached at which there are large increases in membrane conductances, maximal K + efflux, and anoxic de polarization (e.g., Chance et aI., 1962; Vyskocil et aI., 1972;Siesj6, 1978;Blass and Gibson, 1979;Hansen, 1985). 155of mitochondrial reactants were replaced by shifts toward reduction, but rates of reaccumulation of K + , spilled into the extracellular space by neuronal activation, remained unchanged. Only during severe hypoxia (Pao2 less than 20 mm Hg) was it possible in some animals to record a slowing in the reaccumulation of K + 0 without provoca tion of spreading cortical depression. These data indicate that ion transport activity in cerebral cortex is more re fractory to hypoxia than is mitochondrial redox func tioning. They suggest an in vivo parallel to the "cushion ing" effect of mitochondria in vitro, in which oxygen consumption remains constant despite fluctuations in ox ygenation and redox ratios, and also that there may be a greater anaerobic capacity to provide energy for ion transport in mammalian brain than has previously been appreciated. K ey Words: Brain oxygenation-Cy tochrome oxidase-Hypoxia-Mitochondria-Potas sium -Spectrophotometry.It remains difficult, however, to define brain ox ygen sufficiency in physiological terms. In part, this is due to the difficulty in extrapolating effects of anoxia to those produced by hypoxia because anoxia-induced changes occur so rapidly and be cause hypoxia-induced alterations do not reach maxima. Also, little is known of the relationships between brain metabolism and ion transport during hypoxia since high-energy intermediates are rela tively unchanged, at least by mild hypoxia (Si...

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 95%

mentioning

confidence: 99%

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Potassium Ion Homeostasis and Mitochondrial Redox Activity in Brain: Relative Changes as Indicators of Hypoxia

Milito

Raffin

Rosenthal

et al. 1988

J Cereb Blood Flow Metab

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“…The responses were consistently oxidative as long as cerebral blood flow (CBF) and oxygen supply were adequate. By contrast, during moderate hypoxia or impaired CBF, the NADH baseline redox level became reduced and neuron excitation was accompanied by a further transient reduction [20,22,27,29,30].…”

Section: Redox Responses In Excited Brain Tissue In Vivomentioning

confidence: 89%

“…Effectiveness of the correction was demonstrated by the intra-arterial injection of a bolus of saline to dilute Hb, which brightened the cortical surface yet did not affect the corrected NADH signal [19]. Also, during both hypoxia or ischemia, NADH and cytochrome a,a3 redox levels became reduced, even though blood volume increases in the former but decreases in the latter case [5,[20][21][22][23].…”

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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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An Evaluation of Linear Model Analysis Techniques for Processing Images of Microcirculation Activity

Mayhew

Zheng

et al. 1998

NeuroImage

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Sequences of images of the cortical surface can be processed to reveal information about the cortical microcirculation, regional cerebral blood flow (rCBF), and changes induced by neuronal activity. This study examined the use of different analysis methodologies on intrinsic optical images taken from rat sensory motor cortex and testes. Generalized linear model (GLM) analysis was used and compared with standard signal processing methods including principal component analysis. The GLM method has been used by Friston et al. (1994, Hum. Brain Map., 1: 214-220) in the analysis of functional magnetic resonance imagery to identify regions of focal activity. We investigated the use of this method to analyze video image data of the modulation of rCBF from rat cortex. The results revealed spatiotemporal variations in rCBF in response to stimulation within local regions of cortex. The advantage of the GLM method is that it augments ordinary signal processing methods with an estimate of statistical reliability. The use of different wavelengths of illumination reveals spatial structures with different temporal relationships. In image time series data collected under green and red illumination a phase difference was found in the low frequency approximately 0.1 Hz vasomotion oscillation. This phase difference occurred in data from both cortex and testes. A possible explanation of these differences is that the spectral absorption characteristics of the tissue reflect changes in the volume proportions of the different hemoglobin derivatives in interacting with the modulation of the volume of blood. It is suggested that the combination of these effects produces the phase differences we detect.

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Oxygen insufficiency during hypoxic hypoxia in rat brain cortex

Cited by 37 publications

References 25 publications

Potassium Ion Homeostasis and Mitochondrial Redox Activity in Brain: Relative Changes as Indicators of Hypoxia

Potassium Ion Homeostasis and Mitochondrial Redox Activity in Brain: Relative Changes as Indicators of Hypoxia

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

An Evaluation of Linear Model Analysis Techniques for Processing Images of Microcirculation Activity

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