A blood–brain barrier overview on structure, function, impairment, and biomarkers of integrity

Fluids and Barriers of the CNS, Год журнала: 2020, Номер 17(1)

Опубликована: Ноя. 18, 2020

Abstract The blood–brain barrier is playing a critical role in controlling the influx and efflux of biological substances essential for brain’s metabolic activity as well neuronal function. Thus, functional structural integrity BBB pivotal to maintain homeostasis brain microenvironment. different cells structures contributing developing this are summarized along with functions that plays at brain–blood interface. We also explained shear stress maintaining integrity. Furthermore, we elaborated on clinical aspects correlate between disruption neurological pathological conditions. Finally, discussed several biomarkers can help assess permeability in-vitro or in-vivo briefly explain their advantages disadvantages.

Язык: Английский

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Dual microglia effects on blood brain barrier permeability induced by systemic inflammation

Nature Communications, Год журнала: 2019, Номер 10(1)

Опубликована: Дек. 20, 2019

Abstract Microglia survey brain parenchyma, responding to injury and infections. also respond systemic disease, but the role of blood–brain barrier (BBB) integrity in this process remains unclear. Using simultaneous vivo imaging, we demonstrated that inflammation induces CCR5-dependent migration resident microglia cerebral vasculature. Vessel-associated initially maintain BBB via expression tight-junction protein Claudin-5 make physical contact with endothelial cells. During sustained inflammation, phagocytose astrocytic end-feet impair function. Our results show play a dual maintaining implications for elucidating how immune-activation impacts neural functions.

Язык: Английский

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The blood–brain barrier: Structure, regulation and drug delivery

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Май 25, 2023

Abstract Blood–brain barrier (BBB) is a natural protective membrane that prevents central nervous system (CNS) from toxins and pathogens in blood. However, the presence of BBB complicates pharmacotherapy for CNS disorders as most chemical drugs biopharmaceuticals have been impeded to enter brain. Insufficient drug delivery into brain leads low therapeutic efficacy well aggravated side effects due accumulation other organs tissues. Recent breakthrough materials science nanotechnology provides library advanced with customized structure property serving powerful toolkit targeted delivery. In-depth research field anatomical pathological study on further facilitates development brain-targeted strategies enhanced crossing. In this review, physiological different cells contributing are summarized. Various emerging permeability regulation crossing including passive transcytosis, intranasal administration, ligands conjugation, coating, stimuli-triggered disruption, overcome obstacle highlighted. Versatile systems ranging organic, inorganic, biologics-derived their synthesis procedures unique physio-chemical properties summarized analyzed. This review aims provide an up-to-date comprehensive guideline researchers diverse fields, offering perspectives system.

Язык: Английский

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Gut microbes and metabolites as modulators of blood-brain barrier integrity and brain health

Gut Microbes, Год журнала: 2019, Номер 11(2), С. 135 - 157

Опубликована: Авг. 1, 2019

The human gastrointestinal (gut) microbiota comprises diverse and dynamic populations of bacteria, archaea, viruses, fungi, protozoa, coexisting in a mutualistic relationship with the host. When intestinal homeostasis is perturbed, function tract other organ systems, including brain, can be compromised. gut proposed to contribute blood-brain barrier disruption pathogenesis neurodegenerative diseases. While progress being made, better understanding interactions between microbes host cells, impact these have on signaling from brain now required. In this review, we summarise current evidence their metabolites integrity function, communication networks which they may modulate. We also discuss potential modulation strategies as therapeutic tools for promoting restoring health.

Язык: Английский

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Blood-brain barrier dysfunction in ischemic stroke: targeting tight junctions and transporters for vascular protection

AJP Cell Physiology, Год журнала: 2018, Номер 315(3), С. C343 - C356

Опубликована: Июнь 27, 2018

The blood-brain barrier (BBB) is a physical and biochemical that precisely controls cerebral homeostasis. It also plays central role in the regulation of blood-to-brain flux endogenous exogenous xenobiotics associated metabolites. This accomplished by molecular characteristics brain microvessel endothelial cells such as tight junction protein complexes functional expression influx efflux transporters. One pathophysiological features ischemic stroke disruption BBB, which significantly contributes to development injury subsequent neurological impairment. Biochemical BBB damage include decreased altered organization constituent proteins well modulation Therefore, there critical need for novel therapeutic strategies can protect against dysfunction (i.e., vascular protection) setting stroke. Such targeting junctions ensure they maintain their correct structure or transporters control physiological substrates protection In this review, we will describe mechanisms microvascular lead following onset Additionally, utilize state-of-the-art knowledge provide insights on pharmacological be developed confer

Язык: Английский

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Glioblastoma multiforme (GBM): An overview of current therapies and mechanisms of resistance

Pharmacological Research, Год журнала: 2021, Номер 171, С. 105780 - 105780

Опубликована: Июль 21, 2021

Язык: Английский

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Neuroinflammation, Stroke, Blood-Brain Barrier Dysfunction, and Imaging Modalities

Stroke, Год журнала: 2022, Номер 53(5), С. 1473 - 1486

Опубликована: Апрель 7, 2022

Maintaining blood-brain barrier (BBB) integrity is crucial for the homeostasis of central nervous system. Structurally comprising BBB, brain endothelial cells interact with pericytes, astrocytes, neurons, microglia, and perivascular macrophages in neurovascular unit. Brain ischemia unleashes a profound neuroinflammatory response to remove damaged tissue prepare repair. However, intense neuroinflammation occurring during acute phase stroke associated BBB breakdown, neuronal injury, worse neurological outcomes. Here, we critically discuss role ischemic pathology, focusing on interactions between system peripheral immune responses. We highlight inflammation-driven injury mechanisms stroke, including oxidative stress, increased MMP (matrix metalloproteinase) production, microglial activation, infiltration into tissue. provide an updated overview imaging techniques vivo detection permeability, leukocyte infiltration, upregulation cell adhesion molecules following injury. possibility clinical implementation modalities assess stroke-associated potential image-guided diagnosis treatment. summarize results from several studies evaluating efficacy anti-inflammatory interventions stroke. Although convincing preclinical evidence suggests that promising target thus far, translating these setting has proved difficult. Due dual inflammation progression damage, more research needed mechanistically understand when begins transition This could have important implications treatment by informing time- context-specific therapeutic interventions.

Язык: Английский

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Signaling pathways involved in ischemic stroke: molecular mechanisms and therapeutic interventions

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Июль 6, 2022

Abstract Ischemic stroke is caused primarily by an interruption in cerebral blood flow, which induces severe neural injuries, and one of the leading causes death disability worldwide. Thus, it great necessity to further detailly elucidate mechanisms ischemic find out new therapies against disease. In recent years, efforts have been made understand pathophysiology stroke, including cellular excitotoxicity, oxidative stress, cell processes, neuroinflammation. meantime, a plethora signaling pathways, either detrimental or neuroprotective, are also highly involved forementioned pathophysiology. These pathways closely intertwined form complex network. Also, these reveal therapeutic potential, as targeting could possibly serve approaches stroke. this review, we describe categorize them based on pathophysiological processes they participate in. Therapeutic associated with mentioned above, discussed. Meanwhile, clinical trials regarding potentially target involved, summarized details. Conclusively, review elucidated potential molecular related underlying summarize targeted various pathophysiology, particular reference future prospects for treating

Язык: Английский

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Interaction of Microglia and Astrocytes in the Neurovascular Unit

Frontiers in Immunology, Год журнала: 2020, Номер 11

Опубликована: Июль 8, 2020

The interaction between microglia and astrocytes significantly influences neuroinflammation. Microglia/astrocytes, part of the neurovascular unit (NVU), are activated by various brain insults. local extracellular intracellular signals determine their characteristics switch phenotypes. Microglia into two polarization states: pro-inflammatory phenotype (M1 A1) anti-inflammatory (M2 A2). During neuroinflammation, induced stroke or lipopolysaccharides, more sensitive to pathogens damage, thus initially M1 phenotype, produce common inflammatory such as IL- 1 TNF-α trigger reactive A1 phenotype. These can be amplified not only self-feedback loop microglial activation, but also unique anatomy structure astrocytes. As pathology further progresses, resulting in environmental changes, M1-like M2 crosstalk with A2. While communicate simultaneously neurons blood vessels maintain function blood-brain barrier (BBB), subtle changes may identified responded astrocytes, possibly transferred microglia. Although both have different functional characteristics, they achieve immune "optimization" through mutual communication cooperation NVU build a cascaded network amplification.

Язык: Английский

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Transcytosis to Cross the Blood Brain Barrier, New Advancements and Challenges

Frontiers in Neuroscience, Год журнала: 2019, Номер 12

Опубликована: Янв. 11, 2019

The blood brain barrier (BBB) presents a formidable challenge to the delivery of drugs into brain. Several strategies aim overcome this obstacle and promote efficient specific crossing through BBB therapeutically relevant agents. One those uses physiological process receptor-mediated transcytosis (RMT) transport cargo endothelial cells toward parenchyma. Recent developments in our understanding intracellular trafficking receptor binding as well protein engineering nanotechnology have potentiated opportunities for treatment CNS diseases using RMT. In mini-review, current structure is discussed, recent findings exemplifying critical advances RMT-mediated drug are briefly presented.

Язык: Английский

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