Effects of brain oxygenation on metabolic, hemodynamic, ionic and electrical responses to spreading depression in the rat

Sonn, Judith; Mayevsky, Avraham

doi:10.1016/s0006-8993(00)02827-4

Cited by 54 publications

(43 citation statements)

References 16 publications

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“…Our data show that both hypoxia and reduced perfusion pressure transform the large but short-lasting CSDinduced hyperemia into a broad response consisting of hypoperfusion superimposed on the rising phase of an attenuated hyperemia. Our findings are in agreement with a previous qualitative study describing the impact of hypoxia or bilateral carotid occlusion on the CBF response to CSD (Sonn and Mayevsky, 2000) and suggest that, under moderateto-severe hypoxic/ischemic conditions, the normal vasodilatory neurovascular coupling in rat brain is replaced by a vasoconstrictive neurovascular coupling response. Our data also support the notion that anoxic depolarization and periinfarct spreading depressions worsen the metabolism-flow mismatch in ischemic tissue not only by increasing the energy demand but also by reducing the blood supply (Shin et al, 2006).…”

Section: Discussionsupporting

confidence: 93%

“…Under physiologic conditions, the vasodilator coupling during CSD predominates in anesthetized rats. Under nonphysiologic conditions, such as systemic hypoxia and reduced cerebral perfusion pressure, the vasoconstrictive response can be augmented and become the predominant response to CSD, as previously reported in response to CSD during focal and global ischemia (Shin et al, 2006;Sonn and Mayevsky, 2000;Strong et al, 2007). The observed variability of hypoperfusion response to CSD in previous studies (Ayata et al, 2004;Bures and Buresova, 1956;Duckrow, 1993;Fabricius et al, 1995;Farkas et al, 2007;Lauritzen, 1987;Mayevsky et al, 1998;Osada et al, 2006;Piper et al, 1991;Sonn and Mayevsky, 2000;Tomita et al, 2002Tomita et al, , 2005Van Harreveld and Stamm, 1952;Van Harreveld and Ochs, 1957) may thus be related to differences in baseline systemic physiology (pO 2 , BP), choice of anesthesia, species, and the caliber of vessels from which the recordings are obtained.…”

Section: Discussionmentioning

confidence: 55%

“…In most species under anesthesia, CSD evokes a characteristic hyperemia, nearly doubling the cerebral blood flow (CBF) at its peak. This profound CBF increase starts late during the depolarization phase and outlasts it by a few minutes (Ayata et al, 2004;Bures and Buresova, 1956;Farkas et al, 2007;Lauritzen, 1987;Mayevsky et al, 1998;Piper et al, 1991;Sonn and Mayevsky, 2000). A brief vasoconstriction occasionally precedes the vasodilation leading to an initial small hypoperfusion (Ayata et al, 2004;Osada et al, 2006;Tomita et al, 2002Tomita et al, , 2005Van Harreveld and Stamm, 1952;Van Harreveld and Ochs, 1957), which is augmented by nitric oxide (NO) inhibition (Duckrow, 1993;Fabricius et al, 1995), particularly when [K + ] e is artificially elevated (Dreier et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

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Hypoxia and Hypotension Transform the Blood Flow Response to Cortical Spreading Depression from Hyperemia into Hypoperfusion in the Rat

Sukhotinsky

Dileköz

Moskowitz

et al. 2008

J Cereb Blood Flow Metab

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Cortical spreading depression (CSD) evokes a large cerebral blood flow (CBF) increase in normal rat brain. In contrast, in focal ischemic penumbra, CSD-like periinfarct depolarizations (PID) are mainly associated with hypoperfusion. Because PIDs electrophysiologically closely resemble CSD, we tested whether conditions present in ischemic penumbra, such as tissue hypoxia or reduced perfusion pressure, transform the CSD-induced CBF response in nonischemic rat cortex. Cerebral blood flow changes were recorded using laser Doppler flowmetry in rats subjected to hypoxia, hypotension, or both. Under normoxic normotensive conditions, CSD caused a characteristic transient CBF increase (74±7%) occasionally preceded by a small hypoperfusion (À4±2%). Both hypoxia (pO 2 45 ± 3 mm Hg) and hypotension (blood pressure 42 ± 2 mm Hg) independently augmented this initial hypoperfusion (À14±2% normoxic hypotension; À16±6% hypoxic normotension; À21 ± 5% hypoxic hypotension) and diminished the magnitude of hyperemia (44±10% normoxic hypotension; 43±9% hypoxic normotension; 27±6% hypoxic hypotension). Hypotension and, to a much lesser extent, hypoxia increased the duration of hypoperfusion and the DC shift, whereas CSD amplitude remained unchanged. These results suggest that hypoxia and/or hypotension unmask a vasoconstrictive response during CSD in the rat such that, under nonphysiologic conditions (i.e., mimicking ischemic penumbra), the hyperemic response to CSD becomes attenuated resembling the blood flow response during PIDs.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 55%

Section: Introductionmentioning

confidence: 99%

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Hypoxia and Hypotension Transform the Blood Flow Response to Cortical Spreading Depression from Hyperemia into Hypoperfusion in the Rat

Sukhotinsky

Dileköz

Moskowitz

et al. 2008

J Cereb Blood Flow Metab

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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: 77%

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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“…This conclusion stems from the fact that NADH fluoresces in the blue region upon excitation with near-ultraviolet light (e.g., 365 nm) (Puppels et al, 1999), a wavelength of light near the 380 and 340 nm light used for fura-2 excitation. Furthermore, others have noted either a decrease (Sonn and Mayevsky, 2000) or an increase (Hashimoto et al, 2000) in NADH fluorescence from neocortical SD in vivo. Accordingly, we measured the relative contribution of tissue autofluorescence (i.e., approximate change in NADH fluorescence; n ϭ 9) during SD by registering a separate (but similarly sized) area of interest away from fura-2 cells but within the HOTC tissue and comparing this to fura-2 somatic changes elicited by 380-and 340-nm light excitation.…”

Section: Fluorescence Imagingmentioning

confidence: 99%

P/Q Ca²⁺ channel blockade stops spreading depression and related pyramidal neuronal Ca²⁺ rise in hippocampal organ culture

Kunkler

Kraig

2003

Hippocampus

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Ca2+ channels and pyramidal cell Ca2+ are involved in hippocampal spreading depression (SD), but their roles remain elusive. Accordingly, we characterized Ca2+ changes during SD in CA3 pyramidal neurons and determined whether Ca2+ channel antagonists could prevent SD. SD was induced in hippocampal organotypic cultures (HOTCs), in which experimental conditions can be rigorously controlled. SD was triggered by transient exposure to sodium acetate (NaAc)-based Ringer's coupled to an electrical pulse in the dentate gyrus and its occurrence confirmed with interstitial DC recordings. Pyramidal cell Ca2+ was measured with fura-2 filled cells and was quantified at the soma, proximal and more distal apical dendrites. Regional Ca2+ changes began simultaneously with the triggering pulse of SD and reached three distinct peaks before returning to baseline concomitant with the interstitial DC potential of SD. The first peak occurred within 5 s of the triggering pulse, was smallest, and heralded the onset of SD. The second Ca2+ change was the greatest and reached a peak 6 s later, during the early phase of SD. The third was intermediate in size and occurred 18 s later, as SD reached its maximum interstitial DC change. SD was prevented by nonselective Ca2+ blockade (Ni2+ and Cd2+) but not by either L-Ca2+ channel (nifedipine) or N-Ca2+ channel inhibition (omega-conotoxin GVIA). Importantly, SD was blocked by P/Q Ca2+ channel antagonism (omega-agatoxin-IVA), which also prompted a significant reduction in pyramidal cell Ca2+ change and hyperexcitability. These results show that the spatiotemporal pattern of pyramidal cell Ca2+ change with SD is multiphasic; they provide further evidence that these changes begin before electrophysiologic evidence of SD. Furthermore, they show that P/Q Ca2+ channel antagonism can prevent SD in HOTCs and it appears to do so by preventing the NaAc-induced increased pyramidal cell excitability from NaAc exposure, which may involve altered GABAergic transmission.

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Effects of brain oxygenation on metabolic, hemodynamic, ionic and electrical responses to spreading depression in the rat

Cited by 54 publications

References 16 publications

Hypoxia and Hypotension Transform the Blood Flow Response to Cortical Spreading Depression from Hyperemia into Hypoperfusion in the Rat

Hypoxia and Hypotension Transform the Blood Flow Response to Cortical Spreading Depression from Hyperemia into Hypoperfusion in the Rat

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

P/Q Ca²⁺ channel blockade stops spreading depression and related pyramidal neuronal Ca²⁺ rise in hippocampal organ culture

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Effects of brain oxygenation on metabolic, hemodynamic, ionic and electrical responses to spreading depression in the rat

Cited by 54 publications

References 16 publications

Hypoxia and Hypotension Transform the Blood Flow Response to Cortical Spreading Depression from Hyperemia into Hypoperfusion in the Rat

Hypoxia and Hypotension Transform the Blood Flow Response to Cortical Spreading Depression from Hyperemia into Hypoperfusion in the Rat

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

P/Q Ca2+ channel blockade stops spreading depression and related pyramidal neuronal Ca2+ rise in hippocampal organ culture

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P/Q Ca²⁺ channel blockade stops spreading depression and related pyramidal neuronal Ca²⁺ rise in hippocampal organ culture