On the appearance of non-local MRI in Keplerian accretion discs

We revisit the modal analysis of small perturbations in Keplerian ideal gas flows with constant vertical magnetic field leading to magneto-rotational instability (MRI) using the non-local approach. In the general case, MRI modes are described by a Schr\"odinger-like differential equation with some effective potential including 'repulsive' ($1/r^2$) and 'attractive' ($-1/r^3$) terms and are quantized. In shallow potentials, there are no stationary 'energy levels'. In thin Keplerian accretion discs, the perturbation wavelengths $\lambda=2\pi/k_z$ are smaller than the disc semi-thickness $h$ only in 'deep' potential wells. We find that there is a critical magnetic field for the MRI to develop. The instability arises for magnetic field below this critical value. In thin accretion discs, at low background Alfv\'en velocity $c_A\ll (c_A)_\mathrm{cr}$ the MRI instability increment $\omega$ is suppressed compared to the value obtained in the local perturbation analysis, $\omega\approx -\sqrt{3}\mathrm{i}c_Ak_z$. We also investigate for the first time the case of radially variable background magnetic field.Comment: 13 pages, 13 figures, to be submitted. Comments welcome

Modeling of Kidney Hemodynamics: Probability-Based Topology of an Arterial Network

Through regulation of the extracellular fluid volume, the kidneys provide important long-term regulation of blood pressure. At the level of the individual functional unit (the nephron), pressure and flow control involves two different mechanisms that both produce oscillations. The nephrons are arranged in a complex branching structure that delivers blood to each nephron and, at the same time, provides a basis for an interaction between adjacent nephrons. The functional consequences of this interaction are not understood, and at present it is not possible to address this question experimentally. We provide experimental data and a new modeling approach to clarify this problem. To resolve details of microvascular structure, we collected 3D data from more than 150 afferent arterioles in an optically cleared rat kidney. Using these results together with published micro-computed tomography (μCT) data we develop an algorithm for generating the renal arterial network. We then introduce a mathematical model describing blood flow dynamics and nephron to nephron interaction in the network. The model includes an implementation of electrical signal propagation along a vascular wall. Simulation results show that the renal arterial architecture plays an important role in maintaining adequate pressure levels and the self-sustained dynamics of nephrons

Sleep as a Novel Biomarker and a Promising Therapeutic Target for Cerebral Small Vessel Disease: A Review Focusing on Alzheimer’s Disease and the Blood-Brain Barrier

Cerebral small vessel disease (CSVD) is a leading cause of cognitive decline in elderly people and development of Alzheimer’s disease (AD). Blood–brain barrier (BBB) leakage is a key pathophysiological mechanism of amyloidal CSVD. Sleep plays a crucial role in keeping health of the central nervous system and in resistance to CSVD. The deficit of sleep contributes to accumulation of metabolites and toxins such as beta-amyloid in the brain and can lead to BBB disruption. Currently, sleep is considered as an important informative platform for diagnosis and therapy of AD. However, there are no effective methods for extracting of diagnostic information from sleep characteristics. In this review, we show strong evidence that slow wave activity (SWA) (0–0.5 Hz) during deep sleep reflects glymphatic pathology, the BBB leakage and memory deficit in AD. We also discuss that diagnostic and therapeutic targeting of SWA in AD might lead to be a novel era in effective therapy of AD. Moreover, we demonstrate that SWA can be pioneering non-invasive and bed–side technology for express diagnosis of the BBB permeability. Finally, we review the novel data about the methods of detection and enhancement of SWA that can be biomarker and a promising therapy of amyloidal CSVD and CSVD associated with the BBB disorders. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

Sleep as a Novel Biomarker and a Promising Therapeutic Target for Cerebral Small Vessel Disease: A Review Focusing on Alzheimer’s Disease and the Blood-Brain Barrier

Cerebral small vessel disease (CSVD) is a leading cause of cognitive decline in elderly people and development of Alzheimer’s disease (AD). Blood–brain barrier (BBB) leakage is a key pathophysiological mechanism of amyloidal CSVD. Sleep plays a crucial role in keeping health of the central nervous system and in resistance to CSVD. The deficit of sleep contributes to accumulation of metabolites and toxins such as beta-amyloid in the brain and can lead to BBB disruption. Currently, sleep is considered as an important informative platform for diagnosis and therapy of AD. However, there are no effective methods for extracting of diagnostic information from sleep characteristics. In this review, we show strong evidence that slow wave activity (SWA) (0–0.5 Hz) during deep sleep reflects glymphatic pathology, the BBB leakage and memory deficit in AD. We also discuss that diagnostic and therapeutic targeting of SWA in AD might lead to be a novel era in effective therapy of AD. Moreover, we demonstrate that SWA can be pioneering non-invasive and bed–side technology for express diagnosis of the BBB permeability. Finally, we review the novel data about the methods of detection and enhancement of SWA that can be biomarker and a promising therapy of amyloidal CSVD and CSVD associated with the BBB disorders.Russian Science FoundationRussian Foundation for Basic ResearchMinistry of Science and Higher Education of the Russian FederationPeer Reviewe

Mechanisms of Activation of Brain’s Drainage during Sleep: The Nightlife of Astrocytes

The study of functions, mechanisms of generation, and pathways of movement of cerebral fluids has a long history, but the last decade has been especially productive. The proposed glymphatic hypothesis, which suggests a mechanism of the brain waste removal system (BWRS), caused an active discussion on both the criticism of some of the perspectives and our intensive study of new experimental facts. It was especially found that the intensity of the metabolite clearance changes significantly during the transition between sleep and wakefulness. Interestingly, at the cellular level, a number of aspects of this problem have been focused on, such as astrocytes–glial cells, which, over the past two decades, have been recognized as equal partners of neurons and perform many important functions. In particular, an important role was assigned to astrocytes within the framework of the glymphatic hypothesis. In this review, we return to the “astrocytocentric” view of the BWRS function and the explanation of its activation during sleep from the viewpoint of new findings over the last decade. Our main conclusion is that the BWRS’s action may be analyzed both at the systemic (whole-brain) and at the local (cellular) level. The local level means here that the neuro-glial-vascular unit can also be regarded as the smallest functional unit of sleep, and therefore, the smallest functional unit of the BWRS.Russian Science FoundationPeer Reviewe

Awake chronic mouse model of targeted pial vessel occlusion via photothrombosis

Animal models of stroke are used extensively to study the mechanisms involved in the acute and chronic phases of recovery following stroke. A translatable animal model that closely mimics the mechanisms of a human stroke is essential in understanding recovery processes as well as developing therapies that improve functional outcomes. We describe a photothrombosis stroke model that is capable of targeting a single distal pial branch of the middle cerebral artery with minimal damage to the surrounding parenchyma in awake head-fixed mice. Mice are implanted with chronic cranial windows above one hemisphere of the brain that allow optical access to study recovery mechanisms for over a month following occlusion. Additionally, we study the effect of laser spot size used for occlusion and demonstrate that a spot size with small axial and lateral resolution has the advantage of minimizing unwanted photodamage while still monitoring macroscopic changes to cerebral blood flow during photothrombosis. We show that temporally guiding illumination using real-time feedback of blood flow dynamics also minimized unwanted photodamage to the vascular network. Finally, through quantifiable behavior deficits and chronic imaging we show that this model can be used to study recovery mechanisms or the effects of therapeutics longitudinally.R01 EB021018 - NIBIB NIH HHS; R01 MH111359 - NIMH NIH HHS; R01 NS108472 - NINDS NIH HHSPublished versio

Fluorescent angiography of chicken embryo and photobleaching velocimetry

Fluorescent angiography approach in application to a living chicken embryo is discussed. It provides precise vessel wall detection and demonstrates usefulness for real time monitoring of vasoconstriction and vasodilatation related to self regulation of vascular network as well as to response to external factors. On the other hand, high stability of fluorescence and long period of dye elimination makes variations of fluorescent intensity practically independent from fast variations of blood flow rate. Therefore, we proposed the improvement of fluorescent angiography technique by introduction of photobleaching fluorescent velocimetry approach. We have developed the imaging system for intravital microscopic photobleaching velocimetry and tested it by using a glass capillary tube as a model of blood vessel. We demonstrated high potential of the technique for instant flow velocity distribution profile measurement with high spatial and temporal resolution up to 2 μm and 60 ms, respectively

Impact of the light profile on circadian and homeostatic markers in the sleep-wake switching model

Background and Objectives: The goal of this work is to study the impact of the shape of the 24-hour light profile on the behavior of the «sleep-wake» switching model using physiological markers: the time of minimum core body temperature, the time of melatonin peak of plasma, and sleep and wake times. Based on them, you can conclude about the synchronism between circadian, homeostatic and daily rhythms, which is an important criterion for normal human life. Mathematical model: We used the trigger population model of arousal state dynamics, which demonstrates the most realistic process of “sleep-wake” and is based on numeric experimental data. By the means of a mathematical model, we calculated the values of physiological markers and studied the influence of the daily intensity profile on them. Results: As a result of our study, we have found that the light profile, represented by a harmonic function, differs in its impact from non-differentiated forms of profiles and has a stronger influence on the moments of switching between sleep-wake states than on the duration of these states. Also, in the process of our work, we have shown that the shape of the cycle a light-dark is important in the synchronous regime, while at low values of light intensity (synchronism is absent), it has a negligible effect on the behavior of the system and it is required to proceed to the assessment of their dynamics over time. Conclusion: Features of the shape of the light profile must be taken into account when developing experimental protocols