scholarly journals Spatiotemporal components of sustained functional hyperemia are differentially modulated by locomotion and silenced with vascular chemogenetics

2021 ◽  
Author(s):  
Govind Peringod ◽  
Linhui Yu ◽  
Kartikeya Murari ◽  
Grant R Gordon
Keyword(s):  
Blood Flow ◽  
Cell Activation ◽  
Regional Blood Flow ◽  
Optical Signal ◽  
Functional Hyperemia ◽  
Imaging Data ◽  
Initial State ◽  
Mural Cell ◽  
Response Characteristics ◽  
Sensory Evoked

Neural activity underlying sensation, movement or cognition drives regional blood flow enhancement (termed functional hyperemia) to increase the oxygen supply to respiring cells for as long as needed to meet energy demands. However, functional hyperemia is often studied under anesthesia which typically yields response profiles that appear temporally and spatially homogenous. We have insufficient understanding of the underlying kinetics of oxygen delivery in awake animals, especially during specific behaviours that may influence neurally-driven enhancements in cerebral blood flow. Using widefield intrinsic optical signal imaging in awake, head-fixed but active mice, we demonstrated distinct early and late components to changes in intravascular oxygenation in response to sustained (30s) whisker stimulation. We found that the late component (20-30s), but not the early component (1-5s), was strongly influenced by level of whisking/locomotion in the region of highest response and in surrounding regions. Optical flow analyses revealed complex yet stereotyped spatial properties of the early and late components that were related to location within the optical window and the initial state of the cerebral vasculature. In attempt to control these complex response characteristics, we drove a canonical microvasculature constriction pathway using mural cell Gq-chemogenetic mice. A low-dose of systemic C21 strongly limited both the magnitude and spatial extent of the sensory-evoked hemodynamic response, showing that functional hyperemia can be severely limited by direct mural cell activation. These data provide new insights into the cerebral microcirculation in the awake state and may have implications for interpreting functional imaging data.

scholarly journals Optogenetic Stimulation of GABA Neurons can Decrease Local Neuronal Activity While Increasing Cortical Blood Flow

2015 ◽  
Vol 35 (10) ◽  
pp. 1579-1586 ◽  
Author(s):  
Eitan Anenberg ◽  
Allen W Chan ◽  
Yicheng Xie ◽  
Jeffrey M LeDue ◽  
Timothy H Murphy
Keyword(s):  
Blood Flow ◽  
Neuronal Activity ◽  
Optical Signal ◽  
Laser Speckle ◽  
Inhibitory Neurons ◽  
Gamma Aminobutyric Acid ◽  
Contrast Imaging ◽  
Hemodynamic Responses ◽  
Optogenetic Stimulation ◽  
Sensory Evoked

We investigated the link between direct activation of inhibitory neurons, local neuronal activity, and hemodynamics. Direct optogenetic cortical stimulation in the sensorimotor cortex of transgenic mice expressing Channelrhodopsin-2 in GABAergic neurons (VGAT-ChR2) greatly attenuated spontaneous cortical spikes, but was sufficient to increase blood flow as measured with laser speckle contrast imaging. To determine whether the observed optogenetically evoked gamma aminobutyric acid (GABA)-neuron hemodynamic responses were dependent on ionotropic glutamatergic or GABAergic synaptic mechanisms, we paired optogenetic stimulation with application of antagonists to the cortex. Incubation of glutamatergic antagonists directly on the cortex (NBQX and MK-801) blocked cortical sensory evoked responses (as measured with electroencephalography and intrinsic optical signal imaging), but did not significantly attenuate optogenetically evoked hemodynamic responses. Significant light-evoked hemodynamic responses were still present after the addition of picrotoxin (GABA-A receptor antagonist) in the presence of the glutamatergic synaptic blockade. This activation of cortical inhibitory interneurons can mediate large changes in blood flow in a manner that is by and large not dependent on ionotropic glutamatergic or GABAergic synaptic transmission. This supports the hypothesis that activation of inhibitory neurons can increase local cerebral blood flow in a manner that is not entirely dependent on levels of net ongoing neuronal activity.

Assessment of the incorporation of revascularized fibula grafts used for mandibular reconstruction with F-18-PET

2001 ◽  
Vol 40 (02) ◽  
pp. 51-58 ◽  
Author(s):  
H. Schliephake ◽  
van den Hoff ◽  
W. H. Knapp ◽  
G. Berding
Keyword(s):  
Blood Flow ◽  
Regional Blood Flow ◽  
Venous Blood ◽  
Mandibular Reconstruction ◽  
Reference Region ◽  
Osteoblastic Activity ◽  
Non Union ◽  
Range Of Values ◽  
Measured Input

Summary Aim: Determination of the range of regional blood flow and fluoride influx during normal incorporation of revascularized fibula grafts used for mandibular reconstruction. Evaluation, if healing complications are preceded by typical deviations of these parameters from the normal range. Assessment of the potential influence of using “scaled population-derived” instead of “individually measured” input functions in quantitative analysis. Methods: Dynamic F-l 8-PET images and arterialized venous blood samples were obtained in 11 patients early and late after surgery. Based on kinetic modeling regional blood flow (K1) and fluoride influx (Kmlf) were determined. Results: In uncomplicated cases, early postoperative graft K1 - but not Kmlf -exceeded that of vertebrae as reference region. Kmn values obtained in graft necrosis (n = 2) were below the ranges of values observed in uncomplicated healing (0.01 13-0.0745 ml/min/ml) as well as that of the reference region (0.0154-0.0748). Knf values in mobile non-union were in the lower range - and those in rigid non-union in the upper range of values obtained in stable union (0.021 1-0.0694). If scaled population-derived instead of measured input functions were used for quantification, mean deviations of 23 ± 17% in K1 and 12 ± 16% in Kmlf were observed. Conclusions: Normal healing of predominantly cortical bone transplants is characterized by relatively low osteoblastic activity together with increased perfusion. It may be anticipated that transplant necrosis can be identified by showing markedly reduced F− influx. In case that measured input functions are not available, quantification with scaled population-derived input functions is appropriate if expected differences in quantitative parameters exceed 70%.

Basic Ideas and Principles for Quantifying Regional Blood Flow with Nuclear Medical Techniques

1996 ◽  
Vol 35 (05) ◽  
pp. 181-185 ◽  
Author(s):  
H. Herzog
Keyword(s):  
Blood Flow ◽  
Nuclear Medicine ◽  
Regional Blood Flow ◽  
Visual Presentation ◽  
Regional Cerebral Blood ◽  
Basic Principles ◽  
Parametric Images ◽  
Major Application ◽  
Basic Ideas ◽  
The Brain

SummaryThe measurement of blood flow in various organs and its visual presentation in parametric images is a major application in nuclear medicine. The purpose of this paper is to summarize the most important nuclear medicine procedures used to quantify regional blood flow. Starting with the first concepts introduced by Fick and later by Kety-Schmidt the basic principles of measuring global and regional cerebral blood are discussed and their relationships are explained. Different applications and modifications realized first in PET- and later in SPECT-studies of the brain and other organs are described. The permeability and the extraction of the different radiopharmaceuticals are considered. Finally some important instrumental implications are compared.

Regional Blood Flow Patterns along the Length of the Rodent Cochlea

1987 ◽  
Vol 103 (5) ◽  
pp. 176-181 ◽  
Author(s):  
Norma Slepecky ◽  
Clarence Angelborg ◽  
Hans-Christian Larsen
Keyword(s):  
Blood Flow ◽  
Regional Blood Flow ◽  
Flow Patterns ◽  
Blood Flow Patterns

Neural control of glucose uptake by skeletal muscle after central administration of NMDA

1995 ◽  
Vol 268 (2) ◽  
pp. R492-R497 ◽  
Author(s):  
C. H. Lang ◽  
M. Ajmal ◽  
A. G. Baillie
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Glucose Uptake ◽  
Neural Control ◽  
Plasma Insulin ◽  
Regional Blood Flow ◽  
Muscle Blood Flow ◽  
Whole Body ◽  
Glucose Disposal ◽  
Central Administration

Intracerebroventricular injection of N-methyl-D-aspartate (NMDA) produces hyperglycemia and increases whole body glucose uptake. The purpose of the present study was to determine in rats which tissues are responsible for the elevated rate of glucose disposal. NMDA was injected intracerebroventricularly, and the glucose metabolic rate (Rg) was determined for individual tissues 20-60 min later using 2-deoxy-D-[U-14C]glucose. NMDA decreased Rg in skin, ileum, lung, and liver (30-35%) compared with time-matched control animals. In contrast, Rg in skeletal muscle and heart was increased 150-160%. This increased Rg was not due to an elevation in plasma insulin concentrations. In subsequent studies, the sciatic nerve in one leg was cut 4 h before injection of NMDA. NMDA increased Rg in the gastrocnemius (149%) and soleus (220%) in the innervated leg. However, Rg was not increased after NMDA in contralateral muscles from the denervated limb. Data from a third series of experiments indicated that the NMDA-induced increase in Rg by innervated muscle and its abolition in the denervated muscle were not due to changes in muscle blood flow. The results of the present study indicate that 1) central administration of NMDA increases whole body glucose uptake by preferentially stimulating glucose uptake by skeletal muscle, and 2) the enhanced glucose uptake by muscle is neurally mediated and independent of changes in either the plasma insulin concentration or regional blood flow.

Brain adaptation to chronic hypobaric hypoxia in rats

1992 ◽  
Vol 72 (6) ◽  
pp. 2238-2243 ◽  
Author(s):  
J. C. LaManna ◽  
L. M. Vendel ◽  
R. M. Farrell
Keyword(s):  
Blood Flow ◽  
Motor Cortex ◽  
Microvessel Density ◽  
Hypobaric Hypoxia ◽  
Regional Blood Flow ◽  
Oxygen Availability ◽  
Sensory Cortex ◽  
Hypoxic Exposure ◽  
Normal Brain ◽  
Tissue Po2

Rats were exposed to hypobaric hypoxia (0.5 atm) for up to 3 wk. Hypoxic rats failed to gain weight but maintained normal brain water and ion content. Blood hematocrit was increased by 48% to a level of 71% after 3 wk of hypoxia compared with littermate controls. Brain blood flow was increased by an average of 38% in rats exposed to 15 min of 10% normobaric oxygen and by 23% after 3 h but was not different from normobaric normoxic rats after 3 wk of hypoxia. Sucrose space, as a measure of brain plasma volume, was not changed under any hypoxic conditions. The mean brain microvessel density was increased by 76% in the frontopolar cerebral cortex, 46% in the frontal motor cortex, 54% in the frontal sensory cortex, 65% in the parietal motor cortex, 68% in the parietal sensory cortex, 68% in the hippocampal CA1 region, 57% in the hippocampal CA3 region, 26% in the striatum, and 56% in the cerebellum. The results indicate that hypoxia elicits three main responses that affect brain oxygen availability. The acute effect of hypoxia is an increase in regional blood flow, which returns to control levels on continued hypoxic exposure. Longer-term effects of continued moderate hypoxic exposure are erythropoiesis and a decrease in intercapillary distance as a result of angiogenesis. The rise in hematocrit and the increase in microvessel density together increase oxygen availability to the brain to within normal limits, although this does not imply that tissue PO2 is restored to normal.

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