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Adaptive modulation of brain hemodynamics across stereotyped running episodes.

ABSTRACT: During locomotion, theta and gamma rhythms are essential to ensure timely communication between brain structures. However, their metabolic cost and contribution to neuroimaging signals remain elusive. To finely characterize neurovascular interactions during locomotion, we simultaneously recorded mesoscale brain hemodynamics using functional ultrasound (fUS) and local field potentials (LFP) in numerous brain structures of freely-running overtrained rats. Locomotion events were reliably followed by a surge in blood flow in a sequence involving the retrosplenial cortex, dorsal thalamus, dentate gyrus and CA regions successively, with delays ranging from 0.8 to 1.6 seconds after peak speed. Conversely, primary motor cortex was suppressed and subsequently recruited during reward uptake. Surprisingly, brain hemodynamics were strongly modulated across trials within the same recording session; cortical blood flow sharply decreased after 10-20 runs, while hippocampal responses strongly and linearly increased, particularly in the CA regions. This effect occurred while running speed and theta activity remained constant and was accompanied by an increase in the power of hippocampal, but not cortical, high-frequency oscillations (100-150 Hz). Our findings reveal distinct vascular subnetworks modulated across fast and slow timescales and suggest strong hemodynamic adaptation, despite the repetition of a stereotyped behavior.

SUBMITTER: Bergel A

PROVIDER: S-EPMC7713412 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionHemodynamic parameters in zebrafish receive increasing attention because of their important role in cardiovascular processes such as atherosclerosis, hematopoiesis, sprouting and intussusceptive angiogenesis. To study underlying mechanisms, the precise modulation of parameters like blood flow velocity or shear stress is centrally important. Questions related to blood flow have been addressed in the past in either embryonic or ex vivo-zebrafish models but little information is available for adult animals. Here we describe a pharmacological approach to modulate cardiac and hemodynamic parameters in adult zebrafish in vivo.Materials and methodsAdult zebrafish were paralyzed and orally perfused with salt water. The drugs isoprenaline and sodium nitroprusside were directly applied with the perfusate, thus closely resembling the preferred method for drug delivery in zebrafish, namely within the water. Drug effects on the heart and on blood flow in the submental vein were studied using electrocardiograms, in vivo-microscopy and mathematical flow simulations.ResultsUnder control conditions, heart rate, blood flow velocity and shear stress varied less than ± 5%. Maximal chronotropic effects of isoprenaline were achieved at a concentration of 50 ?mol/L, where it increased the heart rate by 22.6 ± 1.3% (n = 4; p < 0.0001). Blood flow velocity and shear stress in the submental vein were not significantly increased. Sodium nitroprusside at 1 mmol/L did not alter the heart rate but increased blood flow velocity by 110.46 ± 19.64% (p = 0.01) and shear stress by 117.96 ± 23.65% (n = 9; p = 0.03).DiscussionIn this study, we demonstrate that cardiac and hemodynamic parameters in adult zebrafish can be efficiently modulated by isoprenaline and sodium nitroprusside. Together with the suitability of the zebrafish for in vivo-microscopy and genetic modifications, the methodology described permits studying biological processes that are dependent on hemodynamic alterations.

Project description:PurposeTo implement, validate, and apply a self-gated free-running whole-heart five-dimensional (5D) flow MRI framework to evaluate respiration-driven effects on three-dimensional (3D) hemodynamics in a clinical setting.Materials and methodsIn this prospective study, a free-running five-dimensional (5D) flow sequence was implemented with 3D radial sampling, self-gating, and a compressed-sensing reconstruction. The 5D flow was evaluated in a pulsatile phantom and adult participants with aortic and/or valvular disease who were enrolled between May and August 2019. Conventional twofold-accelerated four-dimensional (4D) flow of the thoracic aorta with navigator gating was performed as a reference comparison. Continuous parameters were evaluated for parameter normality and were compared between conventional 4D flow and 5D flow using a signed-rank or two-tailed paired t test. Differences between respiratory states were evaluated using a repeated-measure analysis of variance or a nonparametric Friedman test.ResultsA total of 20 adult participants (mean age, 49 years ± 17 [standard deviation]; 18 men and two women) were included. In vitro 5D flow results showed excellent agreement with conventional 4D flow-derived values (peak and net flow, <7% difference over all quantified planes). Whole-heart 5D flow data were collected in all participants in 7.65 minutes ± 0.35 (acceleration rate = 36.0-76.9) versus 9.88 minutes ± 3.17 for conventional aortic 4D flow. In vivo, 5D flow demonstrated moderate agreement with conventional 4D flow but demonstrated overestimation in net flow and peak velocity (up to 26% and 12%, respectively) in the ascending aorta and underestimation (<12%) in the arch and descending aorta. Respiratory-resolved analyses of caval veins showed significantly increased net and peak flow in the inferior vena cava in end inspiration compared with end expiration, and the opposite trend was shown in the superior vena cava.ConclusionA free-running 5D flow MRI framework consistently captured cardiac and respiratory motion-resolved 3D hemodynamics in less than 8 minutes. Supplemental material is available for this article. © RSNA, 2020.

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Adaptive modulation of brain hemodynamics across stereotyped running episodes.

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