Involvement of Astrocytes in the Formation, Maintenance, and Function of the Blood–Brain Barrier

Cells, Год журнала: 2024, Номер 13(2), С. 150 - 150

Опубликована: Янв. 12, 2024

The blood-brain barrier (BBB) is a fundamental structure that protects the composition of brain by determining which ions, metabolites, and nutrients are allowed to enter from blood or leave it towards circulation. BBB structurally composed layer capillary endothelial cells (BCECs) bound each other through tight junctions (TJs). However, its development as well maintenance properties controlled contact BCECs: pericytes, glial cells, even neurons themselves. Astrocytes seem, in particular, have very important role controlling most BBB. Here, we will focus on these latter since comprehension their roles physiology has been continuously expanding, including ability participate neurotransmission complex functions such learning memory. Accordingly, pathological conditions alter astrocytic can BBB's integrity, thus compromising many activities. In this review, also refer different kinds vitro models used study properties, evidencing modifications under conditions.

Язык: Английский

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Innate immune sensors and regulators at the blood brain barrier: focus on toll-like receptors and inflammasomes as mediators of neuro-immune crosstalk and inflammation

Journal of Neuroinflammation, Год журнала: 2025, Номер 22(1)

Опубликована: Фев. 15, 2025

Cerebral endothelial cells (CEC) that form the brain capillaries are principal constituents of blood barrier (BBB), main active interface between and which plays a protective role by restricting infiltration pathogens, harmful substances immune into while allowing entry essential nutrients. Aberrant CEC function often leads to increased permeability BBB altering bidirectional communication bloodstream facilitating extravasation brain. In addition their as gatekeepers BBB, exhibit cell properties they can receive transmit signals partly via release inflammatory effectors in pathological conditions. express innate receptors, including toll like receptors (TLRs) inflammasomes first sensors exogenous or endogenous dangers initiators responses drive neural dysfunction degeneration. Accumulating evidence indicates activation TLRs compromises integrity, promotes aberrant neuroimmune interactions modulates both systemic neuroinflammation, common features neurodegenerative psychiatric diseases central nervous system (CNS) infections injuries. The goal present review is provide an overview pivotal roles played discuss molecular cellular mechanisms contribute disruption neuroinflammation especially context traumatic ischemic injuries infections. We will focus on most recent advances literature reports field highlight knowledge gaps. future research directions advance our understanding contribution potential at promising therapeutic targets wide variety conditions

Язык: Английский

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Cerebromicrovascular mechanisms contributing to long COVID: implications for neurocognitive health

GeroScience, Год журнала: 2025, Номер unknown

Опубликована: Янв. 7, 2025

Abstract Long COVID (also known as post-acute sequelae of SARS-CoV-2 infection [PASC] or post-COVID syndrome) is characterized by persistent symptoms that extend beyond the acute phase infection, affecting approximately 10% to over 30% those infected. It presents a significant clinical challenge, notably due pronounced neurocognitive such brain fog. The mechanisms underlying these effects are multifactorial, with mounting evidence pointing central role cerebromicrovascular dysfunction. This review investigates key pathophysiological contributing cerebrovascular dysfunction in long and their impacts on health. We discuss how endothelial tropism direct vascular trigger dysfunction, impaired neurovascular coupling, blood–brain barrier disruption, resulting compromised cerebral perfusion. Furthermore, appears induce mitochondrial enhancing oxidative stress inflammation within cells. Autoantibody formation following also potentially exacerbates injury, chronic ongoing compromise. These factors collectively contribute emergence white matter hyperintensities, promote amyloid pathology, may accelerate neurodegenerative processes, including Alzheimer’s disease. emphasizes critical advanced imaging techniques assessing health need for targeted interventions address complications. A deeper understanding essential advance treatments mitigate its long-term consequences.

Язык: Английский

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Blood-brain barrier disruption: a culprit of cognitive decline?

Fluids and Barriers of the CNS, Год журнала: 2024, Номер 21(1)

Опубликована: Авг. 7, 2024

Cognitive decline covers a broad spectrum of disorders, not only resulting from brain diseases but also systemic diseases, which seriously influence the quality life and expectancy patients. As highly selective anatomical functional interface between circulation, blood-brain barrier (BBB) plays pivotal role in maintaining homeostasis normal function. The pathogenesis underlying cognitive may vary, nevertheless, accumulating evidences support BBB disruption as most prevalent contributing factor. This mainly be attributed to inflammation, metabolic dysfunction, cell senescence, oxidative/nitrosative stress excitotoxicity. However, direct evidence showing that causes is scarce, interestingly, manipulation opening alone exert beneficial or detrimental neurological effects. A overview present literature shows close relationship decline, risk factors disruption, well cellular molecular mechanisms disruption. Additionally, we discussed possible leading by potential therapeutic strategies prevent enhance repair. review aims foster more investigations on early diagnosis, effective therapeutics, rapid restoration against would yield better outcomes patients with dysregulated function, although their causative has yet been completely established.

Язык: Английский

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Nanoparticles for efficient drug delivery and drug resistance in glioma: New perspectives

CNS Neuroscience & Therapeutics, Год журнала: 2024, Номер 30(5)

Опубликована: Май 1, 2024

Abstract Gliomas are the most common primary tumors of central nervous system, with glioblastoma multiforme (GBM) having highest incidence, and their therapeutic efficacy depends primarily on extent surgical resection postoperative chemotherapy. The role intracranial blood–brain barrier occurrence drug‐resistant gene O6‐methylguanine‐DNA methyltransferase have greatly limited chemotherapeutic agents in patients GBM made it difficult to achieve expected clinical response. In recent years, rapid development nanotechnology has brought new hope for treatment tumors. Nanoparticles (NPs) shown great potential tumor therapy due unique properties such as light, heat, electromagnetic effects, passive targeting. Furthermore, NPs can effectively load drugs, significantly reduce side effects improve efficacy, showing chemotherapy glioma. this article, we reviewed mechanisms glioma drug resistance, physicochemical NPs, advances resistance. We aimed provide perspectives

Язык: Английский

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Post-acute sequelae of SARS-CoV-2 infection (Long COVID) in older adults

GeroScience, Год журнала: 2024, Номер unknown

Опубликована: Июнь 14, 2024

Язык: Английский

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Nobiletin and Eriodictyol Suppress Release of IL-1β, CXCL8, IL-6, and MMP-9 from LPS, SARS-CoV-2 Spike Protein, and Ochratoxin A-Stimulated Human Microglia

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(2), С. 636 - 636

Опубликована: Янв. 14, 2025

Neuroinflammation is involved in various neurological and neurodegenerative disorders which the activation of microglia one key factors. In this study, we examined anti-inflammatory effects flavonoids nobiletin (5,6,7,8,3′,4′-hexamethoxyflavone) eriodictyol (3′,4′,5,7-tetraxydroxyflavanone) on human cell line stimulated by either lipopolysaccharide (LPS), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) full-length Spike protein (FL-Spike), or mycotoxin ochratoxin A (OTA). Human were preincubated with (10, 50, 100 µM) for h, following which, they 24 h. The inflammatory mediators interleukin-1 beta (IL-1β), chemokine (C-X-C motif) ligand 8 (CXCL8), IL-6, matrix metalloproteinase-9 (MMP-9) quantified culture supernatant enzyme-linked immunosorbent assay (ELISA). Both significantly inhibited LPS, FL-Spike, OTA-stimulated release IL-1β, CXCL8, MMP-9 at 50 µM, while, most cases, was also effective 10 pronounced reductions µM. These findings suggest that both are potent inhibitors pathogen-stimulated microglial mediators, highlighting their potential therapeutic application neuroinflammatory diseases, such as long COVID.

Язык: Английский

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Exploring the Pathophysiology of Long COVID: The Central Role of Low-Grade Inflammation and Multisystem Involvement

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(12), С. 6389 - 6389

Опубликована: Июнь 9, 2024

Long COVID (LC), also referred to as Post COVID-19 Condition, Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), and other terms, represents a complex multisystem disease persisting after the acute phase COVID-19. Characterized by myriad symptoms across different organ systems, LC presents significant diagnostic management challenges. Central disorder is role low-grade inflammation, non-classical inflammatory response that contributes chronicity diversity observed. This review explores pathophysiological underpinnings LC, emphasizing importance inflammation core component. By delineating pathogenetic relationships clinical manifestations this article highlights necessity for an integrated approach employs both personalized medicine standardized protocols aimed at mitigating long-term consequences. The insights gained not only enhance our understanding but inform development therapeutic strategies could be applicable chronic conditions with similar features.

Язык: Английский

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Long COVID: Molecular Mechanisms and Detection Techniques

International Journal of Molecular Sciences, Год журнала: 2023, Номер 25(1), С. 408 - 408

Опубликована: Дек. 28, 2023

Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), has emerged a significant health concern following the COVID-19 pandemic. Molecular mechanisms underlying occurrence and progression long COVID include viral persistence, immune dysregulation, endothelial dysfunction, neurological involvement, highlight need for further research to develop targeted therapies this condition. While clearer picture clinical symptomatology is shaping, many molecular are yet be unraveled, given their complexity high level interaction with other metabolic pathways. This review summarizes some most important symptoms associated that occur in well relevant techniques can used understanding pathogen, its affinity towards host, possible outcomes host-pathogen interaction.

Язык: Английский

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Neurovascular unit, neuroinflammation and neurodegeneration markers in brain disorders

Frontiers in Cellular Neuroscience, Год журнала: 2024, Номер 18

Опубликована: Окт. 25, 2024

Neurovascular unit (NVU) inflammation via activation of glial cells and neuronal damage plays a critical role in neurodegenerative diseases. Though the exact mechanism disease pathogenesis is not understood, certain biomarkers provide valuable insight into pathogenesis, severity, progression therapeutic efficacy. These markers can be used to assess pathophysiological status brain including neurons, astrocytes, microglia, oligodendrocytes, specialized microvascular endothelial cells, pericytes, NVU, blood-brain barrier (BBB) disruption. Damage or derangements tight junction (TJ), adherens (AdJ), gap (GJ) components BBB lead increased permeability neuroinflammation various disorders disorders. Thus, neuroinflammatory evaluated blood, cerebrospinal fluid (CSF), tissues determine neurological progression, responsiveness. Chronic common age-related Alzheimer's (AD), Parkinson's (PD), dementia. Neurotrauma/traumatic injury (TBI) also leads acute chronic responses. The expression some may altered many years even decades before onset In this review, we discuss neuroinflammation, neurodegeneration associated with disorders, especially those neurovascular pathologies. CSF, tissues. Neurofilament light (NfL), ubiquitin C-terminal hydrolase-L1 (UCHL1), fibrillary acidic protein (GFAP), Ionized calcium-binding adaptor molecule 1 (Iba-1), transmembrane 119 (TMEM119), aquaporin, endothelin-1, platelet-derived growth factor receptor beta (PDGFRβ) are important markers. Recent BBB-on-a-chip modeling offers promising potential for providing an in-depth understanding neurotherapeutics. Integration these clinical practice could potentially enhance early diagnosis, monitor improve outcomes.

Язык: Английский

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