Pericyte Control of Blood Flow Across Microvascular Zones in the Central Nervous System

Annual Review of Physiology, Journal Year: 2021, Volume and Issue: 84(1), P. 331 - 354

Published: Oct. 21, 2021

The vast majority of the brain's vascular length is composed capillaries, where our understanding blood flow control remains incomplete. This review synthesizes current knowledge on across microvascular zones by addressing issues with nomenclature and drawing new developments from in vivo optical imaging single-cell transcriptomics. Recent studies have highlighted important distinctions mural cell morphology, gene expression, contractile dynamics, which can explain observed differences response to vasoactive mediators between arteriole, transitional, capillary zones. Smooth muscle cells arterioles ensheathing pericytes arteriole-capillary transitional zone large-scale, rapid changes flow. In contrast, downstream act slower smaller scales are involved establishing resting tone heterogeneity. Many unresolved remain, including that activate different pericyte types vivo, role pericyte-endothelial communication conducting signals capillaries arterioles, how neurological disease affects these mechanisms.

Language: Английский

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Neurovascular coupling and oxygenation are decreased in hippocampus compared to neocortex because of microvascular differences

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: May 27, 2021

Abstract The hippocampus is essential for spatial and episodic memory but damaged early in Alzheimer’s disease very sensitive to hypoxia. Understanding how it regulates its oxygen supply therefore key designing interventions preserve function. However, studies of neurovascular function the vivo have been limited by relative inaccessibility. Here we compared hippocampal visual cortical awake mice, using two photon imaging individual neurons vessels measures regional blood flow haemoglobin oxygenation. We show that flow, oxygenation coupling were decreased neocortex, because differences both vascular network pericyte endothelial cell Modelling diffusion indicates these features vasculature may restrict availability could explain sensitivity damage during neurological conditions, including disease, where brain’s energy decreased.

Language: Английский

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Stimuli-responsive ferroptosis for cancer therapy

Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 52(12), P. 3955 - 3972

Published: Jan. 1, 2023

This review highlights recent advances in the utilization of various endogenous and exogenous stimuli to activate nanocarrier-based ferroptosis cancer therapy that can be effective treating conventional drug-resistant tumors.

Language: Английский

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Functional ultrasound localization microscopy reveals brain-wide neurovascular activity on a microscopic scale

Nature Methods, Journal Year: 2022, Volume and Issue: 19(8), P. 1004 - 1012

Published: Aug. 1, 2022

The advent of neuroimaging has increased our understanding brain function. While most brain-wide functional imaging modalities exploit neurovascular coupling to map activity at millimeter resolutions, the recording responses microscopic scale in mammals remains privilege invasive electrophysiological or optical approaches, but is mostly restricted either cortical surface vicinity implanted sensors. Ultrasound localization microscopy (ULM) achieved transcranial cerebrovascular flow, up micrometre scales, by localizing intravenously injected microbubbles; however, long acquisition time required detect microbubbles within vessels so far ULM application mainly microvasculature structural imaging. Here we show how can be modified quantify hyperemia dynamically during activation reaching a 6.5-µm spatial and 1-s temporal resolution deep regions rat brain.

Language: Английский

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Non-invasive temporal interference electrical stimulation of the human hippocampus

Nature Neuroscience, Journal Year: 2023, Volume and Issue: 26(11), P. 1994 - 2004

Published: Oct. 19, 2023

Deep brain stimulation (DBS) via implanted electrodes is used worldwide to treat patients with severe neurological and psychiatric disorders. However, its invasiveness precludes widespread clinical use deployment in research. Temporal interference (TI) a strategy for non-invasive steerable DBS using multiple kHz-range electric fields difference frequency within the range of neural activity. Here we report validation concept humans. We field modeling measurements human cadaver verify that locus transcranial TI can be steerably focused hippocampus minimal exposure overlying cortex. then functional magnetic resonance imaging behavioral experiments show focally modulate hippocampal activity enhance accuracy episodic memories healthy Our results demonstrate targeted, electrical deep structures brain.

Language: Английский

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Neurovascular coupling: motive unknown

Trends in Neurosciences, Journal Year: 2022, Volume and Issue: 45(11), P. 809 - 819

Published: Aug. 19, 2022

Language: Английский

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The Neurovasculome: Key Roles in Brain Health and Cognitive Impairment: A Scientific Statement From the American Heart Association/American Stroke Association

Stroke, Journal Year: 2023, Volume and Issue: 54(6)

Published: April 3, 2023

Preservation of brain health has emerged as a leading public priority for the aging world population. Advances in neurovascular biology have revealed an intricate relationship among cells, meninges, and hematic lymphatic vasculature (the neurovasculome) that is highly relevant to maintenance cognitive function. In this scientific statement, multidisciplinary team experts examines these advances, assesses their relevance disease, identifies knowledge gaps, provides future directions.

Language: Английский

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Pericyte remodeling is deficient in the aged brain and contributes to impaired capillary flow and structure

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Oct. 7, 2022

Abstract Deterioration of brain capillary flow and architecture is a hallmark aging dementia. It remains unclear how loss pericytes in these conditions contributes to dysfunction. Here, we conduct cause-and-effect studies by optically ablating adult aged mice vivo. Focal pericyte induces dilation without blood-brain barrier disruption. These abnormal dilations are exacerbated the brain, result increased heterogeneity networks. A subset affected capillaries experience reduced perfusion due steal. Some stall regress, leading connectivity. Remodeling neighboring restores endothelial coverage vascular tone within days. Pericyte remodeling slower resulting regions persistent dilation. findings link disruption structure. They also identify as therapeutic target preserve dynamics.

Language: Английский

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Direct vascular contact is a hallmark of cerebral astrocytes

Cell Reports, Journal Year: 2022, Volume and Issue: 39(1), P. 110599 - 110599

Published: April 1, 2022

Astrocytes establish extensive networks via gap junctions that allow each astrocyte to connect indirectly the vasculature. However, proportion of astrocytes directly associated with blood vessels is unknown. Here, we quantify structural contacts cortical vasculature in vivo. We show all are connected at least one vessel. Moreover, contact more deeper layers where vessel density known be higher. Further examination different brain regions reveals only hippocampus, which has lowest investigated regions, harbors single no apparent vascular connection. In summary, almost gray matter have direct addition glial network, a access may represent complementary pathway for metabolite uptake and distribution.

Language: Английский

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Neurovascular coupling mechanisms in health and neurovascular uncoupling in Alzheimer’s disease

Brain, Journal Year: 2022, Volume and Issue: 145(7), P. 2276 - 2292

Published: May 13, 2022

Abstract To match the metabolic demands of brain, mechanisms have evolved to couple neuronal activity vasodilation, thus increasing local cerebral blood flow and delivery oxygen glucose active neurons. Rather than relying on feedback signals such as consumption or glucose, main signalling pathways rely release vasoactive molecules by neurons astrocytes, which act contractile cells. Vascular smooth muscle cells pericytes are associated with arterioles capillaries, respectively, relax induce vasodilation. Much progress has been made in understanding complex neurovascular coupling, but issues contributions capillary astrocyte calcium signal remain contentious. Study coupling is especially important dysregulation a prominent feature Alzheimer’s disease. In this article we will discuss developments controversies finish discussing current knowledge concerning uncoupling

Language: Английский

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