scholarly journals Imaging the construction of capillary networks in the neonatal mouse brain

2021 ◽  
Vol 118 (26) ◽  
pp. e2100866118
Author(s):  
Vanessa Coelho-Santos ◽  
Andrée-Anne Berthiaume ◽  
Sharon Ornelas ◽  
Heidi Stuhlmann ◽  
Andy Y. Shih
Keyword(s):  
Blood Flow ◽  
Brain Diseases ◽  
Brain Capillary ◽  
Capillary Networks ◽  
Two Photon ◽  
Capillary Bed ◽  
Flow Through ◽  
And Function ◽  
Blood Brain Barrier Integrity

Capillary networks are essential for distribution of blood flow through the brain, and numerous other homeostatic functions, including neurovascular signal conduction and blood–brain barrier integrity. Accordingly, the impairment of capillary architecture and function lies at the root of many brain diseases. Visualizing how brain capillary networks develop in vivo can reveal innate programs for cerebrovascular growth and repair. Here, we use longitudinal two-photon imaging through noninvasive thinned skull windows to study a burst of angiogenic activity during cerebrovascular development in mouse neonates. We find that angiogenesis leading to the formation of capillary networks originated exclusively from cortical ascending venules. Two angiogenic sprouting activities were observed: 1) early, long-range sprouts that directly connected venules to upstream arteriolar input, establishing the backbone of the capillary bed, and 2) short-range sprouts that contributed to expansion of anastomotic connectivity within the capillary bed. All nascent sprouts were prefabricated with an intact endothelial lumen and pericyte coverage, ensuring their immediate perfusion and stability upon connection to their target vessels. The bulk of this capillary expansion spanned only 2 to 3 d and contributed to an increase of blood flow during a critical period in cortical development.

scholarly journals Brain capillary pericytes exert a substantial but slow influence on blood flow

2020 ◽  
Author(s):  
David A. Hartmann ◽  
Andrée-Anne Berthiaume ◽  
Roger I. Grant ◽  
Sarah A. Harrill ◽  
Tegan Noonan ◽  
...  
Keyword(s):  
Blood Flow ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Two Photon Microscopy ◽  
Capillary Networks ◽  
Mural Cells ◽  
Complementary Approach ◽  
Blood Flow Control ◽  
Capillary Bed

The majority of the brain’s vasculature is comprised of intricate capillary networks lined by capillary pericytes. However, it remains unclear whether capillary pericytes contribute to blood flow control. Using two-photon microscopy to observe and manipulate single capillary pericytes in vivo, we find their optogenetic stimulation decreases lumen diameter and blood flow, but with slower kinetics than mural cells of upstream pial and pre-capillary arterioles. This slow, optogenetically-induced vasoconstriction was inhibited by the clinically-used vasodilator fasudil, a Rho kinase inhibitor that blocks contractile machinery. Capillary pericytes were also slower to constrict back to baseline following hypercapnia-induced dilation, and relax towards baseline following optogenetically-induced vasoconstriction. In a complementary approach, optical ablation of single capillary pericytes led to sustained local dilation and a doubling of blood cell flux in capillaries lacking pericyte contact. Altogether these data indicate that capillary pericytes contribute to basal blood flow resistance and slow modulation of blood flow throughout the capillary bed.

scholarly journals Local IP3 receptor–mediated Ca2+ signals compound to direct blood flow in brain capillaries

2021 ◽  
Vol 7 (30) ◽  
pp. eabh0101
Author(s):  
Thomas A. Longden ◽  
Amreen Mughal ◽  
Grant W. Hennig ◽  
Osama F. Harraz ◽  
Bo Shui ◽  
...  
Keyword(s):  
Blood Flow ◽  
High Amplitude ◽  
Ip3 Receptor ◽  
Brain Capillary ◽  
Capillary Endothelial Cells ◽  
Compound Events ◽  
Flow Through ◽  
Large Clusters ◽  
Small Clusters

Healthy brain function depends on the finely tuned spatial and temporal delivery of blood-borne nutrients to active neurons via the vast, dense capillary network. Here, using in vivo imaging in anesthetized mice, we reveal that brain capillary endothelial cells control blood flow through a hierarchy of IP3 receptor–mediated Ca2+ events, ranging from small, subsecond protoevents, reflecting Ca2+ release through a small number of channels, to high-amplitude, sustained (up to ~1 min) compound events mediated by large clusters of channels. These frequent (~5000 events/s per microliter of cortex) Ca2+ signals are driven by neuronal activity, which engages Gq protein–coupled receptor signaling, and are enhanced by Ca2+ entry through TRPV4 channels. The resulting Ca2+-dependent synthesis of nitric oxide increases local blood flow selectively through affected capillary branches, providing a mechanism for high-resolution control of blood flow to small clusters of neurons.

scholarly journals High-speed volumetric two-photon fluorescence imaging of neurovascular dynamics

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jiang Lan Fan ◽  
Jose A. Rivera ◽  
Wei Sun ◽  
John Peterson ◽  
Henry Haeberle ◽  
...  
Keyword(s):  
Blood Flow ◽  
High Speed ◽  
Laser Scanning ◽  
Three Dimensional ◽  
Laser Scanning Microscopy ◽  
Fluorescence Signal ◽  
Imaging Method ◽  
Spatiotemporal Resolution ◽  
Two Photon

AbstractUnderstanding the structure and function of vasculature in the brain requires us to monitor distributed hemodynamics at high spatial and temporal resolution in three-dimensional (3D) volumes in vivo. Currently, a volumetric vasculature imaging method with sub-capillary spatial resolution and blood flow-resolving speed is lacking. Here, using two-photon laser scanning microscopy (TPLSM) with an axially extended Bessel focus, we capture volumetric hemodynamics in the awake mouse brain at a spatiotemporal resolution sufficient for measuring capillary size and blood flow. With Bessel TPLSM, the fluorescence signal of a vessel becomes proportional to its size, which enables convenient intensity-based analysis of vessel dilation and constriction dynamics in large volumes. We observe entrainment of vasodilation and vasoconstriction with pupil diameter and measure 3D blood flow at 99 volumes/second. Demonstrating high-throughput monitoring of hemodynamics in the awake brain, we expect Bessel TPLSM to make broad impacts on neurovasculature research.

scholarly journals Label-free concurrent 5-modal microscopy (Co5M) resolves unknown spatio-temporal processes in wound healing

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Markus Seeger ◽  
Christoph Dehner ◽  
Dominik Jüstel ◽  
Vasilis Ntziachristos
Keyword(s):  
Wound Healing ◽  
Label Free ◽  
Third Harmonic ◽  
Two Photon ◽  
Non Invasive ◽  
Photon Excitation ◽  
Free Mode ◽  
Spatio Temporal ◽  
And Function

AbstractThe non-invasive investigation of multiple biological processes remains a methodological challenge as it requires capturing different contrast mechanisms, usually not available with any single modality. Intravital microscopy has played a key role in dynamically studying biological morphology and function, but it is generally limited to resolving a small number of contrasts, typically generated by the use of transgenic labels, disturbing the biological system. We introduce concurrent 5-modal microscopy (Co5M), illustrating a new concept for label-free in vivo observations by simultaneously capturing optoacoustic, two-photon excitation fluorescence, second and third harmonic generation, and brightfield contrast. We apply Co5M to non-invasively visualize multiple wound healing biomarkers and quantitatively monitor a number of processes and features, including longitudinal changes in wound shape, microvascular and collagen density, vessel size and fractality, and the plasticity of sebaceous glands. Analysis of these parameters offers unique insights into the interplay of wound closure, vasodilation, angiogenesis, skin contracture, and epithelial reformation in space and time, inaccessible by other methods. Co5M challenges the conventional concept of biological observation by yielding multiple simultaneous parameters of pathophysiological processes in a label-free mode.

scholarly journals Studies of the Hemopoietic Microenvironment. II. Effect of Erythropoietin on the Splenic Microvasculature of Polycythemic CF1 Mice

Blood ◽  
1972 ◽  
Vol 39 (6) ◽  
pp. 809-813 ◽  
Author(s):  
Robert S. McCuskey ◽  
Howard A. Meineke ◽  
Stephen M. Kaplan
Keyword(s):  
Stem Cells ◽  
Blood Flow ◽  
Single Dose ◽  
Pancreatic Tissue ◽  
Linear Velocity ◽  
Hemopoietic Microenvironment ◽  
Microvascular Response ◽  
Flow Through

Abstract The effect of erythropoietin on the splenic microvascular system of polycythemic CF1 mice was studied using in vivo microscopic methods. Administration of a single dose (3 U) of erythropoietin resulted in an increase in the linear velocity of blood flow through the splenic sinusoids and a reduction in the number of sinusoids storing blood. This response was first seen 4-6 hr after injection; it persisted for 48 hr and was reduced markedly by 72 hr. By 120 hr the spleens were indistinguishable from controls. The response was specific for erythrogenic tissue, since no response was seen in the adjacent nonerythropoietic pancreatic tissue. The results suggest that the splenic microvascular response to erythropoietin may be indirect and may be mediated by the release of a vasoactive metabolite from the erythrogenic tissues surrounding the sinusoids. Erythropoietin-sensitive stem cells are suggested to be the source of such a metabolite.

General principles of echocardiography

2016 ◽  
Author(s):  
Madalina Garbi ◽  
Jan D’hooge ◽  
Evgeny Shkolnik
Keyword(s):  
Blood Flow ◽  
Image Interpretation ◽  
Three Dimensional ◽  
Two Dimensional ◽  
Post Processing ◽  
Ultrasound Waves ◽  
Advantages And Disadvantages ◽  
Biologic Effects ◽  
Flow Through ◽  
And Function

Echocardiography uses ultrasound waves to generate images of cardiovascular structures and to display information regarding the blood flow through these structures. Knowledge of basic ultrasound principles and current technology is essential for image interpretation and for optimal use of equipment during image acquisition and post-processing. This chapter starts by presenting the physics of ultrasound and the construction and function of instruments. Image formation, optimization, display, presentation, storage, and communication are explained. Advantages and disadvantages of available imaging modes (M-mode, two-dimensional, and three-dimensional) are detailed and imaging artefacts are illustrated. The potential biologic effects of ultrasound and the need for quality assurance are discussed.

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