The pathobiology of neurovascular aging

Neuron, Journal Year: 2025, Volume and Issue: 113(1), P. 49 - 70

Published: Jan. 1, 2025

Language: Английский

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Elucidating hemodynamics and neuro-glio-vascular signaling using rodent fMRI

Trends in Neurosciences, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Despite extensive functional mapping studies using rodent magnetic resonance imaging (fMRI), interpreting the fMRI signals in relation to their neuronal origins remains challenging due hemodynamic nature of response. Ultra high-resolution fMRI, beyond merely enhancing spatial specificity, has revealed vessel-specific responses, highlighting distinct contributions intracortical arterioles and venules signals. This 'single-vessel' approach shifts paradigm enabling its integration with other neuroimaging modalities investigate neuro-glio-vascular (NGV) signaling underlying a variety brain dynamics. Here, we review emerging trend combining multimodal opto/chemogenetic neuromodulation genetically encoded biosensors for cellular circuit-specific recording, offering unprecedented opportunities cross-scale dynamic models.

Language: Английский

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Estimation of fluid flow velocities in cortical brain tissue driven by the microvasculature

Interface Focus, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 4, 2025

We present a modelling framework for describing bulk fluid flow in brain tissue. Within this framework, using computational simulation, we estimate velocities the grey matter parenchyma due to static or slowly varying water potential gradients—hydrostatic pressure gradients and osmotic gradients. Working with situation that experimental evidence some model parameter estimates, as point out, are presently insufficient precisely, explore feasible ranges resulting range of estimates. consider effect realistic microvascular architecture (extracted from mouse cortical matter). Although estimated small magnitude (e.g. comparison blood velocities), passive transport solutes can be relevant process when considering larger molecules transported over distances. compare velocity magnitudes filtration pulsations. Filtration lead continuous directed parenchyma, while pulsation-driven is (at least partly) reversible. For first time, vascular on distribution tissue sample ca 1 mm 3 conclude both pulsations potentially potent drivers flow.

Language: Английский

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Fast and accessible morphology-free functional fluorescence imaging analysis

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 20, 2025

Abstract Optical calcium imaging is a powerful tool for recording neural activity across wide range of spatial scales, from dendrites and spines to whole-brain through two-photon widefield microscopy. Traditional methods analyzing functional data rely heavily on features, such as the compact shapes somas, extract regions interest their associated temporal traces. This dependency can introduce biases in time trace estimation limit applicability these different neuronal morphologies scales. To address limitations, Graph Filtered Temporal Dictionary Learning (GraFT) uses graph-based approach identify components based shared rather than proximity, enhancing generalizability diverse datasets. Here we present significant advancements GraFT algorithm, including integration more efficient solver L1 least absolute shrinkage selection operator (LASSO) problem application compressive sensing techniques reduce computational complexity. By employing random projections dimensionality, achieve substantial speedups while maintaining analytical accuracy. These significantly accelerate making it scalable larger complex Moreover, increase accessibility, developed graphical user interface facilitate running outputs GraFT. Finally, demonstrate utility beyond meso-scale imaging, vascular axonal imaging.

Language: Английский

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Interleukin-34-dependent perivascular macrophages promote vascular function in the brain

Immunity, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

The development of most macrophages depends on the colony-stimulating factor 1 (CSF-1) receptor, which has two ligands: CSF-1 and interleukin-34 (IL-34). While IL-34 is required for homeostasis microglia, parenchymal in central nervous system (CNS), it unclear whether brain border-associated (BAMs) also depend this cytokine. Here, we demonstrated that embryonic murine BAMs choroid plexus, leptomeninges, perivascular spaces CSF-1, while was critical their maintenance adulthood. In brain, Il34 expressed by mural cells fibroblasts, its transgenic deletion these interrupted BAM maintenance. deficiency coincided with transcriptional changes vascular cells, leading to increased flow velocity vasomotion pial penetrating arterioles. Similarly, Mrc1CreCsf1rfl/fl mice lacking CD206+ exhibited hemodynamics arterial networks. These findings reveal a crosstalk between CNS regulating cerebrovascular function.

Language: Английский

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Modal Analysis of Cerebrovascular Effects for Digital Health Integration of Neurostimulation Therapies—A Review of Technology Concepts

Brain Sciences, Journal Year: 2024, Volume and Issue: 14(6), P. 591 - 591

Published: June 10, 2024

Transcranial electrical stimulation (tES) is increasingly recognized for its potential to modulate cerebral blood flow (CBF) and evoke cerebrovascular reactivity (CVR), which are crucial in conditions like mild cognitive impairment (MCI) dementia. This study explores the impact of tES on neurovascular unit (NVU), employing a physiological modeling approach simulate vascular response electric fields generated by tES. Utilizing FitzHugh–Nagumo model neuroelectrical activity, we demonstrate how can initiate responses such as vasoconstriction followed delayed vasodilation arterioles, potentially modulated combination local metabolic demands autonomic regulation (pivotal locus coeruleus). Here, four distinct pathways within NVU were modeled reflect complex interplay between synaptic astrocytic influences, perivascular potassium dynamics, smooth muscle cell responses. Modal analysis revealed characteristic dynamics these pathways, suggesting that oscillatory may finely tune tone modulating stiffness elasticity vessel walls, possibly also impacting endothelial glycocalyx function. The findings underscore therapeutic vis-à-vis blood-brain barrier safety coupling function needing precise modulation dynamics. technology review supports human-in-the-loop integration leveraging digital health technologies personalized management flow, offering new avenues treating disorders. Future studies should aim optimize parameters using computational validate models clinical settings, enhancing understanding health.

Language: Английский

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Modeling of blood flow dynamics in the rat somatosensory cortex

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 14, 2024

Abstract The cerebral microvasculature forms a dense network of interconnected blood vessels where flow is modulated partly by astrocytes. Increased neuronal activity stimulates astrocytes to release vasoactive substances at the endfeet, altering diameters connected vessels. Our study simulated coupling between variations and vessel diameter changes driven astrocytic in rat somatosensory cortex. We developed framework with three key components: vasculature synthesized morphologies, fluid dynamics model compute each vascular segment, stochastic process replicating effect endfeet on radii. was validated against experimental values from literature across cortical depths. found that local vasodilation astrocyte increased flow, especially capillaries, exhibiting layer-specific response deeper layers. Additionally, highest variability occurred emphasizing their role perfusion regulation. discovered impacts localized, clustered manner, most segments influenced two neighboring endfeet. These insights enhance our understanding neurovascular guide future research flow-related diseases.

Language: Английский

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Microfluctuations in Capillary Lumens Independent of Pericyte Lining Density in the Anesthetized Mouse Cortex

Microcirculation, Journal Year: 2024, Volume and Issue: 31(8)

Published: Sept. 16, 2024

ABSTRACT Objective This study aimed to examine the spatiotemporal coherence of capillary lumen fluctuations in relation spatial variations pericyte lining cortex anesthetized mice. Methods Two‐photon microscopic angiography data (previously published) were reanalyzed, and diameter at rest with vascular mural cells measured along centerlines. Results Relatively large diameters capillaries (5.5 μm) coincided a dense lining, while small (4.3 had sparse lining. Temporal frequency about 0.1 Hz an amplitude 0.5 μm, which negatively correlated density. Spatial analysis further revealed common pattern but temporal differed. The lumens locally distinct from those neighboring locations, suggesting intrinsic independent Conclusions Capillary brain exhibit slow microfluctuations that are These could affect distribution flowing blood may be important for homogenizing their networks.

Language: Английский

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Why do central nervous system barriers host a diverse immune landscape?

Trends in Immunology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

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