SARS-CoV-2 deregulates the vascular and immune functions of brain pericytes via Spike protein

Neurobiology of Disease, Journal Year: 2021, Volume and Issue: 161, P. 105561 - 105561

Published: Nov. 13, 2021

Coronavirus disease 19 (COVID-19) is a respiratory illness caused by severe acute syndrome coronavirus-2 (SARS-CoV-2). COVID-19 pathogenesis causes vascular-mediated neurological disorders via elusive mechanisms. SARS-CoV-2 infects host cells the binding of viral Spike (S) protein to transmembrane receptor, angiotensin-converting enzyme 2 (ACE2). Although brain pericytes were recently shown abundantly express ACE2 at neurovascular interface, their response S still be elucidated. Using cell-based assays, we found that expression in human vascular was increased upon exposure. Pericytes exposed underwent profound phenotypic changes associated with an elongated and contracted morphology accompanied enhanced contractile myofibrogenic proteins, such as α-smooth muscle actin (α-SMA), fibronectin, collagen I, neurogenic locus notch homolog protein-3 (NOTCH3). On functional level, exposure promoted acquisition calcium (Ca

Language: Английский

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Neurovascular dysfunction in glaucoma

Progress in Retinal and Eye Research, Journal Year: 2023, Volume and Issue: 97, P. 101217 - 101217

Published: Sept. 30, 2023

Retinal ganglion cells, the neurons that die in glaucoma, are endowed with a high metabolism requiring optimal provision of oxygen and nutrients to sustain their activity. The timely regulation blood flow is, therefore, essential supply firing active areas glucose they need for energy. Many glaucoma patients suffer from vascular deficits including reduced flow, impaired autoregulation, neurovascular coupling dysfunction, blood-retina/brain-barrier breakdown. These processes tightly regulated by community cells known as unit comprising neurons, endothelial pericytes, Müller astrocytes, microglia. In this review, takes center stage we examine ability its members regulate interactions how function might be altered during glaucomatous stress. Pericytes receive special attention based on recent data demonstrating key role physiological pathological conditions. Of particular interest is discovery characterization tunneling nanotubes, thin actin-based conduits connect distal which play roles complex spatial temporal distribution within retinal capillary network. We discuss cellular molecular mechanisms pathophysiological implications, while highlighting opportunities develop strategies protection regeneration improve functional outcomes glaucoma.

Language: Английский

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Neurovascular coupling impairment as a mechanism for cognitive deficits in COVID-19

Brain Communications, Journal Year: 2024, Volume and Issue: 6(2)

Published: Jan. 1, 2024

Abstract Components that comprise our brain parenchymal and cerebrovascular structures provide a homeostatic environment for proper neuronal function to ensure normal cognition. Cerebral insults (e.g. ischaemia, microbleeds infection) alter cellular physiologic processes within the neurovascular unit contribute cognitive dysfunction. COVID-19 has posed significant complications during acute convalescent stages in multiple organ systems, including brain. Cognitive impairment is prevalent complication patients, irrespective of severity SARS-CoV-2 infection. Moreover, overwhelming evidence from vitro, preclinical clinical studies reported SARS-CoV-2-induced pathologies components are associated with impairment. Neurovascular disruption alters coupling response, critical mechanism regulates cerebromicrovascular blood flow meet energetic demands locally active neurons. Normal processing achieved through response involves coordinated action cells (i.e. neurons glia) cell types endothelia, smooth muscle pericytes). However, current work on COVID-19-induced yet investigate as causal factor. Hence, this review, we aim describe SARS-CoV-2's effects how they can impact decline disease. Additionally, explore potential therapeutic interventions mitigate Given great both individuals public health, necessity effort fundamental scientific research application becomes imperative. This integrated endeavour crucial mitigating deficits induced by its subsequent burden especially vulnerable population.

Language: Английский

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Hippocampal subfield abnormalities and biomarkers of pathologic brain changes: from SARS-CoV-2 acute infection to post-COVID syndrome

EBioMedicine, Journal Year: 2023, Volume and Issue: 94, P. 104711 - 104711

Published: July 13, 2023

Cognitive deficits are among the main disabling symptoms in COVID-19 patients and post-COVID syndrome (PCS). Within brain regions, hippocampus, a key region for cognition, has shown vulnerability to SARS-CoV-2 infection. Therefore, vivo detailed evaluation of hippocampal changes PCS patients, validated on post-mortem samples at acute phase, would shed light into relationship between cognition.Hippocampal subfields volume, microstructure, perfusion were evaluated 84 compared 33 controls. Associations with blood biomarkers, including glial fibrillary acidic protein (GFAP), myelin oligodendrocyte glycoprotein (MOG), eotaxin-1 (CCL11) neurofilament chain (NfL) evaluated. Besides, biomarker immunodetection seven necropsies phase contrasted against eight controls.In analyses revealed that grey matter atrophy is accompanied by altered microstructural integrity, hypoperfusion, functional connectivity patients. Hippocampal structural alterations related cognitive dysfunction, particularly attention memory. GFAP, MOG, CCL11 NfL biomarkers PCS, showed associations volume changes, selective subfields. Moreover, post mortem histology presence increased GFAP reduced MOG concentrations hippocampus phase.The current results evidenced sequalae present cascade pathological indicating axonal damage, astrocyte alterations, neuronal injury, already from phase.Nominative Grant FIBHCSC 2020 COVID-19. Department Health, Community Madrid. Instituto de Salud Carlos III through project INT20/00079, co-funded European Regional Development Fund "A way make Europe" (JAMG). (ISCIII) Sara Borrell postdoctoral fellowship No. CD22/00043) Union (MDC). predoctoral contract (FI20/000145) (co-funded Europe") (MVS). Fundación para el Conocimiento Madri+d G63-HEALTHSTARPLUS-HSP4 (JAMG, SOM).

Language: Английский

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A tight squeeze: How do we make sense of small changes in microvascular diameter?

The Journal of Physiology, Journal Year: 2023, Volume and Issue: 601(12), P. 2263 - 2272

Published: April 10, 2023

The brain is an energetically demanding tissue which, to function adequately, requires constant fine tuning of its supporting blood flow, and hence energy supply. Whilst flow was traditionally believed be regulated only by vascular smooth muscle cells on arteries arterioles supplying the brain, recent work has suggested a critical role for capillary pericytes, which are also contractile. This concept evoked some controversy, especially over relative contributions capillaries control cerebral flow. Here we outline why pericytes in privileged position First discuss evidence, fundamental equations, describe how small starting diameter capillaries, compared upstream arterioles, confers potentially greater than total resistance. Then suggest that faster time frame low branch order dilate response local demands provides niche regulate slower responding arterioles. Finally, stalling, whereby pericyte contraction appears facilitate transient stall circulating cells, exacerbating effect upon

Language: Английский

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Pericytes in the brain and heart: functional roles and response to ischaemia and reperfusion

Cardiovascular Research, Journal Year: 2024, Volume and Issue: unknown

Published: July 26, 2024

In the last 20 years there has been a revolution in our understanding of how blood flow is regulated many tissues. Whereas it used to be thought that essentially all control occurred at arteriole level, now recognised capillary by contractile pericytes plays key role both regulating physiologically and reducing clinically-relevant pathological conditions. this article we compare contrast brain cardiac regulate cerebral coronary flow, focusing mainly on events ischemia. The beds differ dramatically morphology, yet cases pericyte-mediated constriction restricting after ischemia possibly other We conclude with suggestions for therapeutic approaches relaxing pericytes, which may prove useful long term pericyte-induced

Language: Английский

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Neurological complications caused by SARS-CoV-2

Clinical Microbiology Reviews, Journal Year: 2024, Volume and Issue: 37(4)

Published: Sept. 18, 2024

SUMMARYSARS-CoV-2 can not only cause respiratory symptoms but also lead to neurological complications. Research has shown that more than 30% of SARS-CoV-2 patients present neurologic during COVID-19 (A. Pezzini and A. Padovani, Nat Rev Neurol 16:636-644, 2020, https://doi.org/10.1038/s41582-020-0398-3). Increasing evidence suggests invade both the central nervous system (CNS) (M.S. Xydakis, M.W. Albers, E.H. Holbrook, et al. Lancet 20: 753-761, 2021 https://doi.org/10.1016/S1474-4422(21)00182-4 ) peripheral (PNS) (M.N. Soares, M. Eggelbusch, E. Naddaf, J Cachexia Sarcopenia Muscle 13:11-22, 2022, https://doi.org/10.1002/jcsm.12896), resulting in a variety disorders. This review summarized CNS complications caused by infection, including encephalopathy, neurodegenerative diseases, delirium. Additionally, some PNS disorders such as skeletal muscle damage inflammation, anosmia, smell or taste impairment, myasthenia gravis, Guillain-Barré syndrome, ICU-acquired weakness, post-acute sequelae were described. Furthermore, mechanisms underlying SARS-CoV-2-induced discussed, entering brain through retrograde neuronal hematogenous routes, disrupting normal function cytokine storms, inducing cerebral ischemia hypoxia, thus leading Moreover, an overview long-COVID-19 is provided, along with recommendations for care therapeutic approaches experiencing

Language: Английский

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SARS-CoV-2 infects epithelial cells of the blood-cerebrospinal fluid barrier rather than endothelial cells or pericytes of the blood-brain barrier

Fluids and Barriers of the CNS, Journal Year: 2023, Volume and Issue: 20(1)

Published: Oct. 24, 2023

As a consequence of SARS-CoV-2 infection various neurocognitive and neuropsychiatric symptoms can appear, which may persist for several months post infection. However, cell type-specific routes brain underlying mechanisms resulting in neuroglial dysfunction are not well understood.

Language: Английский

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Diabetes as a Pancreatic Microvascular Disease—A Pericytic Perspective

Journal of Histochemistry & Cytochemistry, Journal Year: 2024, Volume and Issue: 72(3), P. 131 - 148

Published: March 1, 2024

Diabetes is not only an endocrine but also a vascular disease. Vascular defects are usually seen as consequence of diabetes. However, at the level pancreatic islet, alterations have been described before symptom onset. Importantly, cellular and molecular mechanisms underlying these early identified, neither how could impact function islet cells. In this review, we will discuss possibility that dysfunction mural cells microvasculature-known pericytes-underlies observed in islets pre-symptomatic stages. Pericytes crucial for homeostasis throughout body, their physiological pathophysiological functions recently started to be explored. A previous study had already raised interest "microvascular" approach With our increased understanding role microvasculature glucose homeostasis, here revisit aspects deregulation contribute diabetes pathogenesis, focusing particular on type 1 (T1D).

Language: Английский

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A Brief Overview of Neutrophils in Neurological Diseases

Biomolecules, Journal Year: 2023, Volume and Issue: 13(5), P. 743 - 743

Published: April 25, 2023

Neutrophils are the most abundant leukocyte in circulation and first line of defense after an infection or injury. have a broad spectrum functions, including phagocytosis microorganisms, release pro-inflammatory cytokines chemokines, oxidative burst, formation neutrophil extracellular traps. Traditionally, neutrophils were thought to be important for acute inflammatory responses, with short half-life more static response infections However, this view has changed recent years showing heterogeneity dynamics, indicating much regulated flexible response. Here we will discuss role aging neurological disorders; specifically, focus on data impact chronic processes their contribution diseases. Lastly, aim conclude that reactive directly contribute increased vascular inflammation age-related

Language: Английский

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