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

Fluids and Barriers of the CNS, Journal Year: 2020, Volume and Issue: 17(1)

Published: Nov. 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.

Language: Английский

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Revisiting the neurovascular unit

Nature Neuroscience, Journal Year: 2021, Volume and Issue: 24(9), P. 1198 - 1209

Published: Aug. 5, 2021

Language: Английский

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Blood-Brain Barrier Dysfunction in CNS Disorders and Putative Therapeutic Targets: An Overview

Pharmaceutics, Journal Year: 2021, Volume and Issue: 13(11), P. 1779 - 1779

Published: Oct. 26, 2021

The blood-brain barrier (BBB) is a fundamental component of the central nervous system (CNS). Its functional and structural integrity vital to maintain homeostasis brain microenvironment by controlling passage substances regulating trafficking immune cells between blood brain. BBB primarily composed highly specialized microvascular endothelial cells. These cells' special features physiological properties are acquired maintained through concerted effort hemodynamic cellular cues from surrounding environment. This complex multicellular system, comprising cells, astrocytes, pericytes, neurons, known as neurovascular unit (NVU). strictly controls transport nutrients metabolites into parenchyma tightly regulated while limiting access potentially harmful via efflux transcytosis metabolic mechanisms. Not surprisingly, disruption has been associated with onset and/or progression major neurological disorders. Although association disease clear, its nature not always evident, specifically regard whether an impaired function results pathological condition or damage primary pathogenic factor prodromal disease. In either case, repairing could be viable option for treating reducing effects CNS this review, we describe structure in both healthy altered/diseased conditions. Additionally, provide overview potential therapeutic targets that leveraged restore concomitant treatment these

Language: Английский

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Magnetic iron oxide nanoparticles for brain imaging and drug delivery

Advanced Drug Delivery Reviews, Journal Year: 2023, Volume and Issue: 197, P. 114822 - 114822

Published: April 21, 2023

Central nervous system (CNS) disorders affect as many 1.5 billion people globally. The limited delivery of most imaging and therapeutic agents into the brain is a major challenge for treatment CNS disorders. With advent nanotechnologies, controlled drugs with nanoparticles holds great promise in overcoming blood-brain barrier (BBB) improving efficacy. In recent years, magnetic iron oxide (MIONPs) have stood out promising theranostic nanoplatform drug they possess unique physical properties biodegradable characteristics. this review, we summarize advances MIONP-based platforms diseases. We firstly introduce methods synthesis surface functionalization MIONPs emphasis on inclusion biocompatible polymers that allow addition tailored physicochemical properties. then discuss vivo applications using MIONPs. Finally, present perspective remaining challenges possible future directions systems.

Language: Английский

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Advancing neurological disorders therapies: Organic nanoparticles as a key to blood-brain barrier penetration

International Journal of Pharmaceutics, Journal Year: 2025, Volume and Issue: 670, P. 125186 - 125186

Published: Jan. 8, 2025

The blood-brain barrier (BBB) plays a vital role in protecting the central nervous system (CNS) by preventing entry of harmful pathogens from bloodstream. However, this also presents significant obstacle when it comes to delivering drugs for treatment neurodegenerative diseases and brain cancer. Recent breakthroughs nanotechnology have paved way creation wide range nanoparticles (NPs) that can serve as carriers diagnosis therapy. Regarding their promising properties, organic NPs potential be used effective drug delivery across BBB based on recent advancements. These remarkable ability penetrate using various mechanisms. This review offers comprehensive examination intricate structure distinct properties BBB, emphasizing its crucial function preserving balance regulating transport ions molecules. disruption conditions such stroke, Alzheimer's disease, Parkinson's disease highlights importance developing creative approaches drugs. Through encapsulation therapeutic molecules precise targeting processes vasculature, NP formulations present hopeful strategy improve BBB. We explore changes pathological investigate factors affect successful into brain. In addition, we most systems associated with shown positive results treating ischemic disorders. opens up new possibilities nanotechnology-based therapies cerebral diseases.

Language: Английский

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The Crucial Role of the Blood–Brain Barrier in Neurodegenerative Diseases: Mechanisms of Disruption and Therapeutic Implications

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(2), P. 386 - 386

Published: Jan. 9, 2025

The blood-brain barrier (BBB) is a crucial structure that maintains brain homeostasis by regulating the entry of molecules and cells from bloodstream into central nervous system (CNS). Neurodegenerative diseases such as Alzheimer's Parkinson's disease, well ischemic stroke, compromise integrity BBB. This leads to increased permeability infiltration harmful substances, thereby accelerating neurodegeneration. In this review, we explore mechanisms underlying BBB disruption, including oxidative stress, neuroinflammation, vascular dysfunction, loss tight junction integrity, in patients with neurodegenerative diseases. We discuss how breakdown contributes neurotoxicity, abnormal accumulation pathological proteins, all which exacerbate neuronal damage facilitate disease progression. Furthermore, potential therapeutic strategies aimed at preserving or restoring function, anti-inflammatory treatments, antioxidant therapies, approaches enhance integrity. Given role neurodegeneration, maintaining its represents promising approach slow prevent progression

Language: Английский

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Emerging Application of Nanorobotics and Artificial Intelligence To Cross the BBB: Advances in Design, Controlled Maneuvering, and Targeting of the Barriers

ACS Chemical Neuroscience, Journal Year: 2021, Volume and Issue: 12(11), P. 1835 - 1853

Published: May 19, 2021

The blood–brain barrier (BBB) is a prime focus for clinicians to maintain the homeostatic function in health and deliver theranostics brain cancer number of neurological diseases. structural hierarchy situ biochemical signaling BBB neurovascular unit have been primary targets recapitulate into vitro modules. microengineered perfusion systems development 3D cellular organoid culture given major thrust research neuropharmacology. In this review, we on revisiting nanoparticles based bimolecular engineering enable them maneuver, control, target, theranostic payloads across as nanorobots or nanobots. Subsequently provide brief outline specific case studies addressing payload delivery tumor disorders (e.g., Alzheimer's disease, Parkinson's multiple sclerosis, etc.). addition, also address opportunities challenges nanorobots' design. Finally, how computationally powered machine learning (ML) tools artificial intelligence (AI) can be partnered with robotics predict design next generation interact without causing damage, toxicity, malfunctions. content review could references multidisciplinary science clinicians, roboticists, chemists, bioengineers involved cutting-edge pharmaceutical research.

Language: Английский

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Transendothelial Electrical Resistance Measurement across the Blood–Brain Barrier: A Critical Review of Methods

Micromachines, Journal Year: 2021, Volume and Issue: 12(6), P. 685 - 685

Published: June 11, 2021

The blood–brain barrier (BBB) represents the tightest endothelial within cardiovascular system characterized by very low ionic permeability. Our aim was to describe setups, electrodes, and instruments measure electrical resistance across brain microvessels culture models of BBB, as well critically assess influence often neglected physical technical parameters such temperature, viscosity, current density generated different electrode types, surface size, circumference, porosity insert membrane. We demonstrate that these greatly measurement transendothelial resistance/resistivity (TEER) BBB resulting in severalfold differences TEER values same biological model, especially low-TEER range. show elevated medium viscosity significantly increases, while higher membrane decreases values. data measured chopstick electrodes can be threefold than chamber due size geometry, distribution inhomogeneity. An additional shunt at circumference inserts results lower A detailed description setups is crucial for correct interpretation comparison models.

Language: Английский

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The role of amyloid oligomers in neurodegenerative pathologies

International Journal of Biological Macromolecules, Journal Year: 2021, Volume and Issue: 181, P. 582 - 604

Published: March 23, 2021

Many neurodegenerative diseases are rooted in the activities of amyloid-like proteins which possess conformations that spread to healthy proteins. These include Alzheimer's disease (AD), Parkinson's (PD), Huntington's (HD) and amyotrophic lateral sclerosis (ALS). While their clinical manifestations vary, protein-level mechanisms remarkably similar. Aberrant monomeric undergo conformational shifts, facilitating aggregation formation solid fibrils. However, there is growing evidence intermediate oligomeric stages key drivers neuronal toxicity. Analysis protein dynamics complicated by fact nucleation growth not a linear pathway. Feedback within this pathway results exponential acceleration aggregation, but exerted oligomers fibrils can alter cellular interactions environment as whole. The resulting cascade effects likely contributes late onset accelerating progression disorders widespread they have on body. In review we explore associated with AD, PD, HD ALS, well common aggregation. From this, identify core elements pathological been targeted for therapies, may become future therapeutic targets.

Language: Английский

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Novel Methods and Approaches for Safety Evaluation of Nanoparticle Formulations: A Focus Towards In Vitro Models and Adverse Outcome Pathways

Frontiers in Pharmacology, Journal Year: 2021, Volume and Issue: 12

Published: Sept. 9, 2021

Nanotoxicology is an emerging field employed in the assessment of unintentional hazardous effects produced by nanoparticles (NPs) impacting human health and environment. The nanotoxicity affects range between induction cellular stress cytotoxicity. reasons so far reported for these toxicological are due to their variable sizes with high surface areas, shape, charge, physicochemical properties, which upon interaction biological components may influence functioning result adverse outcomes (AO). Thus, understanding risk materials now important safety concern development nanotechnology nanomedicine. Since time nanotoxicology has evolved, methods have been majorly relied on vitro cell-based evaluations, while simple not predict complexity involved preclinical clinical conditions concerning pharmacokinetics, organ toxicity, toxicities evidenced through multiple levels. profiles nanoscale nanomaterials nanoformulations delivery drugs therapeutic applications considerable concern. In addition, new nanomedicine formulas lacks regulatory standards. Though vivo studies greatly needed, end parameters used predicting possible toxic various nanoformulations. On other side, increased restrictions animal usage demand need high-throughput assays, there a developing exploring novel evaluate NPs concerns. progress made molecular biology availability several modern techniques offer innovative behavior different using single cells, cell population, whole organisms. This review highlights recent developed evaluation impacts attempts solve problems that come assessment. relevance investigating outcome pathways (AOPs) stressed particular.

Language: Английский

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