Pericyte loss leads to circulatory failure and pleiotrophin depletion causing neuron loss

Nature Neuroscience, Год журнала: 2019, Номер 22(7), С. 1089 - 1098

Опубликована: Июнь 24, 2019

Язык: Английский

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Neuronal regulation of the blood–brain barrier and neurovascular coupling

Nature reviews. Neuroscience, Год журнала: 2020, Номер 21(8), С. 416 - 432

Опубликована: Июль 7, 2020

Язык: Английский

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Regulation of blood–brain barrier integrity by microglia in health and disease: A therapeutic opportunity

Journal of Cerebral Blood Flow & Metabolism, Год журнала: 2020, Номер 40(1_suppl), С. S6 - S24

Опубликована: Сен. 14, 2020

The blood–brain barrier (BBB) is a critical regulator of CNS homeostasis. It possesses physical and biochemical characteristics (i.e. tight junction protein complexes, transporters) that are necessary for the BBB to perform this physiological role. Microvascular endothelial cells require support from astrocytes, pericytes, microglia, neurons, constituents extracellular matrix. This intricate relationship implies existence neurovascular unit (NVU). NVU cellular components can be activated in disease contribute dynamic remodeling BBB. especially true resident immune brain, which polarize into distinct proinflammatory (M1) or anti-inflammatory (M2) phenotypes. Current data indicate M1 pro-inflammatory microglia dysfunction vascular “leak”, while M2 play protective role at Understanding biological mechanisms involved activation provides unique opportunity develop novel treatment approaches neurological diseases. In review, we highlight describe how these phenotypes modulate physiology. Additionally, outline other cell types regulating microglial targeted with focus on ischemic stroke Alzheimer’s disease.

Язык: Английский

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

Nature Neuroscience, Год журнала: 2021, Номер 24(5), С. 633 - 645

Опубликована: Фев. 18, 2021

Язык: Английский

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Targeting pericytes for therapeutic approaches to neurological disorders

Acta Neuropathologica, Год журнала: 2018, Номер 136(4), С. 507 - 523

Опубликована: Авг. 10, 2018

Many central nervous system diseases currently lack effective treatment and are often associated with defects in microvascular function, including a failure to match the energy supplied by blood used on neuronal computation, or breakdown of blood–brain barrier. Pericytes, an under-studied cell type located capillaries, crucial importance regulating diverse functions, such as angiogenesis, barrier, capillary flow movement immune cells into brain. They also form part "glial" scar isolating damaged parts CNS, may have stem cell-like properties. Recent studies suggested that pericytes play role neurological diseases, thus therapeutic target disorders stroke, traumatic brain injury, migraine, epilepsy, spinal cord diabetes, Huntington's disease, Alzheimer's multiple sclerosis, glioma, radiation necrosis amyotrophic lateral sclerosis. Here we report recent advances our understanding pericyte biology discuss how could be targeted develop novel approaches disorders, increasing flow, preserving barrier entry modulating formation vessels in, glial around, regions.

Язык: Английский

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Contractile pericytes determine the direction of blood flow at capillary junctions

Proceedings of the National Academy of Sciences, Год журнала: 2020, Номер 117(43), С. 27022 - 27033

Опубликована: Окт. 13, 2020

The essential function of the circulatory system is to continuously and efficiently supply O2 nutrients necessary meet metabolic demands every cell in body, a which vast capillary networks play key role. Capillary serve an additional important central nervous system: acting as sensory network, they detect neuronal activity form elevated extracellular K+ initiate retrograde, propagating, hyperpolarizing signal that dilates upstream arterioles rapidly increase local blood flow. Yet, little known about how entering this network distributed on branch-to-branch basis reach specific neurons need. Here, we demonstrate capillary-enwrapping projections junctional, contractile pericytes within postarteriole transitional region differentially constrict structurally dynamically determine morphology junctions thereby regulate branch-specific We further found these are capable receiving propagating K+-induced signals through channeling red cells toward initiating signal. By controlling flow at junctions, functionally distinct maintain efficiency effectiveness enabling optimal perfusion brain.

Язык: Английский

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Intracellular transport and regulation of transcytosis across the blood–brain barrier

Cellular and Molecular Life Sciences, Год журнала: 2018, Номер 76(6), С. 1081 - 1092

Опубликована: Дек. 6, 2018

The blood–brain barrier is a dynamic multicellular interface that regulates the transport of molecules between blood circulation and brain parenchyma. Proteins peptides required for homeostasis cross via transcellular transport, but mechanisms control this pathway are not well characterized. Here, we highlight recent studies on intracellular transcytosis across barrier. Endothelial cells at possess an intricate endosomal network allows sorting to diverse cellular destinations. Internalization from plasma membrane, sorting, exocytosis all contribute regulation transcytosis. Transmembrane receptors blood-borne proteins utilize different pathways endothelial cells. Alterations in during diseases central nervous system disruption disease progression. Harnessing can help improve delivery biotherapeutics brain.

Язык: Английский

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Cytokines in CAR T Cell–Associated Neurotoxicity

Frontiers in Immunology, Год журнала: 2020, Номер 11

Опубликована: Дек. 16, 2020

Chimeric antigen receptor (CAR) T cells provide new therapeutic options for patients with relapsed/refractory hematologic malignancies. However, neurotoxicity is a frequent, and potentially fatal, complication. The spectrum of manifestations ranges from delirium language dysfunction to seizures, coma, fatal cerebral edema. This novel syndrome has been designated immune effector cell-associated (ICANS). In this review, we draw an arc our current understanding how systemic local cytokine release act on the CNS, toward possible preventive approaches. We systematically review reported correlations secreted inflammatory mediators in serum/plasma cerebrospinal fluid risk ICANS receiving CAR cell therapy. Possible pathophysiologic impacts CNS are covered detail most promising candidate cytokines, including IL-1, IL-6, IL-15, GM-CSF. To insight into final common pathways inflammation, place context other conditions that associated neurologic dysfunction, sepsis-associated encephalopathy, malaria, thrombotic microangiopathy, infections, hepatic encephalopathy. then what known about interaction components neurovascular unit, endothelial cells, pericytes, astrocytes, microglia neurons respond challenges. Current approaches, corticosteroids blockade IL-1 IL-6 signaling, reviewed role cytokines ICANS. Throughout, point out gaps knowledge approaches investigation mechanism, prevention, treatment

Язык: Английский

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Interactions of SARS-CoV-2 with the Blood–Brain Barrier

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(5), С. 2681 - 2681

Опубликована: Март 6, 2021

Emerging data indicate that neurological complications occur as a consequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The blood–brain barrier (BBB) is critical interface regulates entry circulating molecules into the CNS, and regulated by signals arise from brain blood compartments. In this review, we discuss mechanisms which SARS-CoV-2 interactions with BBB may contribute to dysfunction associated disease 2019 (COVID-19), caused SARS-CoV-2. We consider aspects peripheral disease, such hypoxia systemic inflammatory response syndrome/cytokine storm, well CNS infection viral brain. also contribution risk factors for developing COVID-19 could increase or otherwise damage

Язык: Английский

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

Annual Review of Physiology, Год журнала: 2021, Номер 84(1), С. 331 - 354

Опубликована: Окт. 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.

Язык: Английский

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