scholarly journals Cerebral oxygenation during locomotion is modulated by respiration

2019 ◽  
Author(s):  
Qingguang Zhang ◽  
Morgane Roche ◽  
Kyle W. Gheres ◽  
Emmanuelle Chaigneau ◽  
William D. Haselden ◽  
...  
Keyword(s):  
Neural Activity ◽  
Tissue Oxygenation ◽  
Cerebral Oxygenation ◽  
Oxygen Sensors ◽  
Whole Body ◽  
Lifetime Measurements ◽  
Phosphorescence Lifetime ◽  
Two Photon ◽  
Oxygen Dynamics ◽  
The Brain

AbstractIn the brain, increased neural activity is correlated with an increase of cerebral blood flow and increased tissue oxygenation. However, how cerebral oxygen dynamics are controlled in the behaving animals remains unclear. Here, we investigated to what extent the cerebral oxygenation varies during natural behaviors that change the whole-body homeostasis, specifically exercise. We measured oxygen levels in the cortex of awake, head-fixed mice during locomotion using polarography, spectroscopy, and two-photon phosphorescence lifetime measurements of oxygen sensors. We found that locomotion significantly and globally increases cerebral oxygenation, specifically in areas involved in locomotion, as well as in the frontal cortex and the olfactory bulb. The oxygenation increase persisted when neural activity and functional hyperemia were blocked, occurred both in the tissue and in arteries feeding the brain, and was tightly correlated with respiration rate and the phase of respiration cycle. Thus, respiration provides a dynamic pathway for modulating cerebral oxygenation.

scholarly journals Cerebral oxygenation during locomotion is modulated by respiration

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Qingguang Zhang ◽  
Morgane Roche ◽  
Kyle W. Gheres ◽  
Emmanuelle Chaigneau ◽  
Ravi T. Kedarasetti ◽  
...  
Keyword(s):  
Neural Activity ◽  
Tissue Oxygenation ◽  
Cerebral Oxygenation ◽  
Breathing Rate ◽  
Lifetime Measurements ◽  
Phosphorescence Lifetime ◽  
Two Photon ◽  
Animal Remains ◽  
Oxygen Dynamics ◽  
The Brain

AbstractIn the brain, increased neural activity is correlated with increases of cerebral blood flow and tissue oxygenation. However, how cerebral oxygen dynamics are controlled in the behaving animal remains unclear. We investigated to what extent cerebral oxygenation varies during locomotion. We measured oxygen levels in the cortex of awake, head-fixed mice during locomotion using polarography, spectroscopy, and two-photon phosphorescence lifetime measurements of oxygen sensors. We find that locomotion significantly and globally increases cerebral oxygenation, specifically in areas involved in locomotion, as well as in the frontal cortex and the olfactory bulb. The oxygenation increase persists when neural activity and functional hyperemia are blocked, occurred both in the tissue and in arteries feeding the brain, and is tightly correlated with respiration rate and the phase of respiration cycle. Thus, breathing rate is a key modulator of cerebral oxygenation and should be monitored during hemodynamic imaging, such as in BOLD fMRI.

scholarly journals Origins of 1/f-like tissue oxygenation fluctuations in the murine cortex

2020 ◽  
Author(s):  
Qingguang Zhang ◽  
Kyle W. Gheres ◽  
Patrick J. Drew
Keyword(s):  
Neural Activity ◽  
Power Distribution ◽  
Tissue Oxygenation ◽  
Field Potential ◽  
Two Photon ◽  
Stochastic Fluctuations ◽  
Discrete Nature ◽  
Limited Power ◽  
Band Limited ◽  
The Brain

AbstractThe concentration of oxygen in the brain spontaneously fluctuates, and the power distribution in these fluctuations has 1/f-like dynamics. Though these oscillations have been interpreted as being driven by neural activity, the origins of these 1/f-like oscillations is not well understood. Here, to gain insight of the origin of the 1/f-like oxygen fluctuations, we investigated the dynamics of tissue oxygenation and neural activity in awake behaving mice. We found that oxygen signal recorded from the cortex of mice had 1/f-like spectra. However, band-limited power in the local field potential, did not show corresponding 1/f-like fluctuations. When local neural activity was suppressed, the 1/f-like fluctuations in oxygen concentration persisted. Two-photon measurements of erythrocyte spacing fluctuations (‘stalls’) and mathematical modelling show that stochastic fluctuations in erythrocyte flow and stalling could underlie 1/f-like dynamics in oxygenation. These results show discrete nature of erythrocytes and their irregular flow, rather than neural activity, could drive 1/f-like fluctuations in tissue oxygenation.

Cerebral blood flow and metabolism during exercise: implications for fatigue

2008 ◽  
Vol 104 (1) ◽  
pp. 306-314 ◽  
Author(s):  
Neils H. Secher ◽  
Thomas Seifert ◽  
Johannes J. Van Lieshout
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Perceived Exertion ◽  
Cerebral Oxygenation ◽  
Metabolic Response ◽  
Work Of Breathing ◽  
Whole Body ◽  
Strenuous Exercise ◽  
Glycogen Depletion ◽  
The Brain

During exercise: the Kety-Schmidt-determined cerebral blood flow (CBF) does not change because the jugular vein is collapsed in the upright position. In contrast, when CBF is evaluated by 133Xe clearance, by flow in the internal carotid artery, or by flow velocity in basal cerebral arteries, a ∼25% increase is detected with a parallel increase in metabolism. During activation, an increase in cerebral O2 supply is required because there is no capillary recruitment within the brain and increased metabolism becomes dependent on an enhanced gradient for oxygen diffusion. During maximal whole body exercise, however, cerebral oxygenation decreases because of eventual arterial desaturation and marked hyperventilation-related hypocapnia of consequence for CBF. Reduced cerebral oxygenation affects recruitment of motor units, and supplemental O2 enhances cerebral oxygenation and work capacity without effects on muscle oxygenation. Also, the work of breathing and the increasing temperature of the brain during exercise are of importance for the development of so-called central fatigue. During prolonged exercise, the perceived exertion is related to accumulation of ammonia in the brain, and data support the theory that glycogen depletion in astrocytes limits the ability of the brain to accelerate its metabolism during activation. The release of interleukin-6 from the brain when exercise is prolonged may represent a signaling pathway in matching the metabolic response of the brain. Preliminary data suggest a coupling between the circulatory and metabolic perturbations in the brain during strenuous exercise and the ability of the brain to access slow-twitch muscle fiber populations.

scholarly journals Origins of 1/f-like tissue oxygenation fluctuations in the murine cortex

PLoS Biology ◽  
2021 ◽  
Vol 19 (7) ◽  
pp. e3001298
Author(s):  
Qingguang Zhang ◽  
Kyle W. Gheres ◽  
Patrick J. Drew
Keyword(s):  
Neural Activity ◽  
Tissue Oxygenation ◽  
Field Potential ◽  
Low Frequencies ◽  
Two Photon ◽  
Stochastic Fluctuations ◽  
Discrete Nature ◽  
Limited Power ◽  
Band Limited ◽  
Distribution Of Power

The concentration of oxygen in the brain spontaneously fluctuates, and the distribution of power in these fluctuations has a 1/f-like spectra, where the power present at low frequencies of the power spectrum is orders of magnitude higher than at higher frequencies. Though these oscillations have been interpreted as being driven by neural activity, the origin of these 1/f-like oscillations is not well understood. Here, to gain insight of the origin of the 1/f-like oxygen fluctuations, we investigated the dynamics of tissue oxygenation and neural activity in awake behaving mice. We found that oxygen signal recorded from the cortex of mice had 1/f-like spectra. However, band-limited power in the local field potential did not show corresponding 1/f-like fluctuations. When local neural activity was suppressed, the 1/f-like fluctuations in oxygen concentration persisted. Two-photon measurements of erythrocyte spacing fluctuations and mathematical modeling show that stochastic fluctuations in erythrocyte flow could underlie 1/f-like dynamics in oxygenation. These results suggest that the discrete nature of erythrocytes and their irregular flow, rather than fluctuations in neural activity, could drive 1/f-like fluctuations in tissue oxygenation.

scholarly journals Kilohertz two-photon fluorescence microscopy imaging of neural activity in vivo

2019 ◽  
Author(s):  
Jianglai Wu ◽  
Yajie Liang ◽  
Shuo Chen ◽  
Ching-Lung Hsu ◽  
Mariya Chavarha ◽  
...  
Keyword(s):  
Neural Activity ◽  
Laser Scanning ◽  
Imaging Method ◽  
Spatiotemporal Resolution ◽  
Microscopy Imaging ◽  
Two Photon ◽  
Two Photon Fluorescence ◽  
Photon Fluorescence ◽  
The Brain

Understanding information processing in the brain requires us to monitor neural activity in vivo at high spatiotemporal resolution. Using an ultrafast two-photon fluorescence microscope (2PFM) empowered by all-optical laser scanning, we imaged neural activity in vivo at up to 3,000 frames per second and submicron spatial resolution. This ultrafast imaging method enabled monitoring of both supra- and sub-threshold electrical activity down to 345 μm below the brain surface in head fixed awake mice.

scholarly journals Cerebral Oxygenation during Postasphyxial Seizures in Near-Term Fetal Sheep

2005 ◽  
Vol 25 (7) ◽  
pp. 911-918 ◽  
Author(s):  
Hernan Gonzalez ◽  
Christian J Hunter ◽  
Laura Bennet ◽  
Gordon G Power ◽  
Alistair J Gunn
Keyword(s):  
Blood Flow ◽  
Tissue Oxygenation ◽  
Cerebral Oxygenation ◽  
Immature Brain ◽  
Fetal Sheep ◽  
Blood Temperature ◽  
Cerebral Tissue Oxygenation ◽  
A1 Receptor ◽  
Near Term ◽  
The Brain

After exposure to asphyxia, infants may develop both prolonged, clinically evident seizures and shorter, clinically silent seizures; however, their effect on cerebral tissue oxygenation is unclear. We therefore examined the hypothesis that the increase in oxygen delivery during postasphyxial seizures might be insufficient to meet the needs of increased metabolism, thus causing a fall in tissue oxygenation, in unanesthetized near-term fetal sheep in utero (gestational age 125 ± 1 days). Fetuses were administered an infusion of the specific adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine, followed by 10 mins of asphyxia induced by complete umbilical cord occlusion. The fetuses then recovered for 3 days. Sixty-one episodes of electrophysiologically defined seizures were identified in five fetuses. Tissue PO2 (tPO2) did not change significantly during short seizures (<3.5 mins), 5.2 ± 0.2 versus baseline 5.6 ± 0.1 mm Hg (NS), but fell to 2.2 ± 0.2 mm Hg during seizures lasting more than 3.5 mins ( P<0.001). During prolonged seizures, cortical blood flow did not begin to increase until tPO2 had begun to fall, and then rose more slowly than the increase in metabolism, with a widening of the brain to blood temperature gradient. In conclusion, in the immature brain, during prolonged, but not short seizures, there is a transient mismatch between cerebral blood flow and metabolism leading to significant cerebral deoxygenation.

Quantitative determination of localized tissue oxygen concentration in vivo by two-photon excitation phosphorescence lifetime measurements

2004 ◽  
Vol 97 (5) ◽  
pp. 1962-1969 ◽  
Author(s):  
Egbert G. Mik ◽  
Ton G. van Leeuwen ◽  
Nicolaas J. Raat ◽  
Can Ince
Keyword(s):  
Rat Kidney ◽  
Excitation Wavelength ◽  
Lifetime Measurements ◽  
Phosphorescence Lifetime ◽  
Oxygen Determination ◽  
Two Photon ◽  
Photon Excitation ◽  
Two Photon Excitation

This study describes the use of two-photon excitation phosphorescence lifetime measurements for quantitative oxygen determination in vivo. Doubling the excitation wavelength of Pd-porphyrin from visible light to the infrared allows for deeper tissue penetration and a more precise and confined selection of the excitation volume due to the nonlinear two-photon effect. By using a focused laser beam from a 1,064-nm Q-switched laser, providing 10-ns pulses of 10 mJ, albumin-bound Pd-porphyrin was effectively excited and oxygen-dependent decay of phosphorescence was observed. In vitro calibration of phosphorescence lifetime vs. oxygen tension was performed. The obtained calibration constants were kq = 356 Torr−1·s−1 (quenching constant) and τ0 = 550 μs (lifetime at zero-oxygen conditions) at 37°C. The phosphorescence intensity showed a squared dependency to the excitation intensity, typical for two-photon excitation. In vivo demonstration of two-photon excitation phosphorescence lifetime measurements is shown by step-wise Po2 measurements through the cortex of rat kidney. It is concluded that quantitative oxygen measurements can be made, both in vitro and in vivo , using two-photon excitation oxygen-dependent quenching of phosphorescence. The use of two-photon excitation has the potential to lead to new applications of the phosphorescence lifetime technique, e.g., noninvasive oxygen scanning in tissue at high spatial resolution. To our knowledge, this is the first report in which two-photon excitation is used in the setting of oxygen-dependent quenching of phosphorescence lifetime measurements.

scholarly journals Biocompatible Ir(III) Complexes as Oxygen Sensors for Phosphorescence Lifetime Imaging

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 2898
Author(s):  
Ilya S. Kritchenkov ◽  
Anastasia I. Solomatina ◽  
Daria O. Kozina ◽  
Vitaly V. Porsev ◽  
Victor V. Sokolov ◽  
...  
Keyword(s):  
Near Infrared ◽  
Biological Systems ◽  
Aqueous Media ◽  
Oxygen Sensors ◽  
Quantum Yields ◽  
Complete Agreement ◽  
Phosphorescence Lifetime ◽  
Lifetime Imaging ◽  
Nir Emission ◽  
Phosphorescence Lifetime Imaging

Synthesis of biocompatible near infrared phosphorescent complexes and their application in bioimaging as triplet oxygen sensors in live systems are still challenging areas of organometallic chemistry. We have designed and synthetized four novel iridium [Ir(N^C)2(N^N)]+ complexes (N^C–benzothienyl-phenanthridine based cyclometalated ligand; N^N–pyridin-phenanthroimidazol diimine chelate), decorated with oligo(ethylene glycol) groups to impart these emitters’ solubility in aqueous media, biocompatibility, and to shield them from interaction with bio-environment. These substances were fully characterized using NMR spectroscopy and ESI mass-spectrometry. The complexes exhibited excitation close to the biological “window of transparency”, NIR emission at 730 nm, and quantum yields up to 12% in water. The compounds with higher degree of the chromophore shielding possess low toxicity, bleaching stability, absence of sensitivity to variations of pH, serum, and complex concentrations. The properties of these probes as oxygen sensors for biological systems have been studied by using phosphorescence lifetime imaging experiments in different cell cultures. The results showed essential lifetime response onto variations in oxygen concentration (2.0–2.3 μs under normoxia and 2.8–3.0 μs under hypoxia conditions) in complete agreement with the calibration curves obtained “in cuvette”. The data obtained indicate that these emitters can be used as semi-quantitative oxygen sensors in biological systems.

scholarly journals Has molecular imaging delivered to drug development?

2017 ◽  
Vol 375 (2107) ◽  
pp. 20170112 ◽  
Author(s):  
Philip S. Murphy ◽  
Neel Patel ◽  
Timothy J. McCarthy
Keyword(s):  
Molecular Imaging ◽  
Drug Development ◽  
Clinical Studies ◽  
Pharmaceutical Research ◽  
Whole Body ◽  
Drug Candidate ◽  
Clinical Drug Development ◽  
Target Binding ◽  
The Brain ◽  
Clinical Drug

Pharmaceutical research and development requires a systematic interrogation of a candidate molecule through clinical studies. To ensure resources are spent on only the most promising molecules, early clinical studies must understand fundamental attributes of the drug candidate, including exposure at the target site, target binding and pharmacological response in disease. Molecular imaging has the potential to quantitatively characterize these properties in small, efficient clinical studies. Specific benefits of molecular imaging in this setting (compared to blood and tissue sampling) include non-invasiveness and the ability to survey the whole body temporally. These methods have been adopted primarily for neuroscience drug development, catalysed by the inability to access the brain compartment by other means. If we believe molecular imaging is a technology platform able to underpin clinical drug development, why is it not adopted further to enable earlier decisions? This article considers current drug development needs, progress towards integration of molecular imaging into studies, current impediments and proposed models to broaden use and increase impact. This article is part of the themed issue ‘Challenges for chemistry in molecular imaging’.

Bone-brain crosstalk and potential associated diseases

2016 ◽  
Vol 28 (2) ◽  
Author(s):  
Audrey Rousseaud ◽  
Stephanie Moriceau ◽  
Mariana Ramos-Brossier ◽  
Franck Oury
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Development ◽  
Cognitive Functions ◽  
Intimate Relationship ◽  
Whole Body ◽  
Reciprocal Relationships ◽  
Skeletal Homeostasis ◽  
The Central Nervous System ◽  
The Brain

AbstractReciprocal relationships between organs are essential to maintain whole body homeostasis. An exciting interplay between two apparently unrelated organs, the bone and the brain, has emerged recently. Indeed, it is now well established that the brain is a powerful regulator of skeletal homeostasis via a complex network of numerous players and pathways. In turn, bone via a bone-derived molecule, osteocalcin, appears as an important factor influencing the central nervous system by regulating brain development and several cognitive functions. In this paper we will discuss this complex and intimate relationship, as well as several pathologic conditions that may reinforce their potential interdependence.

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