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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Recent Research Trends in Neuroinflammatory and Neurodegenerative Disorders

Cells, Journal Year: 2024, Volume and Issue: 13(6), P. 511 - 511

Published: March 14, 2024

Neuroinflammatory and neurodegenerative disorders including Alzheimer’s disease (AD), Parkinson’s (PD), traumatic brain injury (TBI) Amyotrophic lateral sclerosis (ALS) are chronic major health disorders. The exact mechanism of the neuroimmune dysfunctions these pathogeneses is currently not clearly understood. These show dysregulated inflammatory responses, activation neurons, glial cells, neurovascular unit damage associated with excessive release proinflammatory cytokines, chemokines, neurotoxic mediators, infiltration peripheral immune cells into brain, as well entry mediators through damaged endothelial blood–brain barrier tight junction proteins. Activation leads to many molecules that cause neuroinflammation neurodegeneration. Gulf War Illness (GWI) myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) also dysfunctions. Currently, there no effective disease-modifying therapeutic options available for diseases. Human induced pluripotent stem cell (iPSC)-derived astrocytes, microglia, pericytes used models drug discovery. This review highlights certain recent trends in neuroinflammatory responses iPSC-derived applications

Language: Английский

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Blood–Brain Barrier-Targeting Nanoparticles: Biomaterial Properties and Biomedical Applications in Translational Neuroscience

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(5), P. 612 - 612

Published: May 10, 2024

Overcoming the blood–brain barrier (BBB) remains a significant hurdle in effective drug delivery to brain. While BBB serves as crucial protective barrier, it poses challenges delivering therapeutic agents their intended targets within brain parenchyma. To enhance for treatment of neurological diseases, several technologies circumvent have been developed last few years. Among them, nanoparticles (NPs) are one most versatile and promising tools. Here, we summarize characteristics NPs that facilitate penetration, including size, shape, chemical composition, surface charge, importantly, conjugation with various biological or synthetic molecules such glucose, transferrin, insulin, polyethylene glycol, peptides, aptamers. Additionally, discuss coating surfactants. A comprehensive overview common vitro vivo models NP penetration studies is also provided. The discussion extends discussing impairment under pathological conditions leveraging alterations delivery. Emphasizing need future uncover inherent properties NPs, review advocates role beyond systems calls efforts translating clinic therapeutics. Overall, stand out highly strategy precise targeting disorders.

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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Applications of hydrogels and nanoparticles in the treatment of traumatic brain injury

Frontiers in Bioengineering and Biotechnology, Journal Year: 2025, Volume and Issue: 12

Published: Jan. 6, 2025

Traumatic brain injury (TBI) represents a significant global public health issue, with effective management posing numerous challenges. The pathophysiology of TBI is typically categorized into two phases: primary and secondary injuries. Secondary involves pathophysiological mechanisms such as blood-brain barrier (BBB) disruption, mitochondrial dysfunction, oxidative stress, inflammatory responses. Current pharmacological strategies often encounter obstacles in treating effectively, primarily due to challenges BBB penetration, inadequate target site accumulation, off-target toxicity. Versatile hydrogels nanoparticles offer potential solutions these limitations. This review discusses recent progress utilizing for treatment over the past 5 years, highlighting their relevance underlying pathophysiology. Hydrogels demonstrate substantial promise addressing injury, providing broad spectrum future therapeutic opportunities.

Language: Английский

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Accelerated fracture healing accompanied with traumatic brain injury: A review of clinical studies, animal models and potential mechanisms

Journal of Orthopaedic Translation, Journal Year: 2025, Volume and Issue: 50, P. 71 - 84

Published: Jan. 1, 2025

The orthopaedic community frequently encounters polytrauma individuals with concomitant traumatic brain injury (TBI) and their fractures demonstrate accelerated fracture union, but the mechanisms remain far from clear. Animal clinical studies robust callus formation at early healing process expedited radiographical union. In humans, in TBI occurs independently of fixation methods across multiple sites. replicate clinically relevant enlarged as characterized by increased tissue volume bone stages. However, refinement standardization models requires further research. quest for its underlying began finding osteogenesis vitro using serum cerebral spinal fluid (CSF) individuals. This has led to investigation myriads brain-derived factors including humoral factors, cytokines, exosomes, mi-RNAs. Further, emerging information interplay between skeletal system central nervous system, roles peripheral nerves neuropeptides regulating regeneration, offers valuable insights future review consolidates findings both experimental studies, elucidating potential enhanced concurrent scenarios that may lay down a foundation develop innovative therapies enhancement conquer non-union. translational this article. comprehensively summarizes observations presence preclinical studies. addition, it also delineates cellular molecular mechanisms. Further detailed into reveal intervention strategies improve thus offering promising avenues applications.

Language: Английский

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Inhibitors of Mammalian Aquaporin Water Channels

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(7), P. 1589 - 1589

Published: March 29, 2019

Aquaporins (AQPs) are water channel proteins that essential to life, being expressed in all kingdoms. In humans, there 13 AQPs, at least one of which is found every organ system. The structural biology the AQP family well-established and many functions for AQPs have been reported health disease. expression linked numerous pathologies including tumor metastasis, fluid dysregulation, traumatic injury. targeted modulation therefore presents an opportunity develop novel treatments diverse conditions. Various techniques such as video microscopy, light scattering fluorescence quenching used test putative inhibitors both AQP-expressing mammalian cells heterologous systems. inherent variability within these methods has caused discrepancy molecules inhibitory experimental system (such tetraethylammonium, acetazolamide, anti-epileptic drugs) no activity others. Some heavy metal ions (that would not be suitable therapeutic use) compound, TGN-020, shown inhibit some AQPs. Clinical trials neuromyelitis optica using anti-AQP4 IgG progress. However, antibodies effect on transport. More research standardize high-throughput assays required identify modulators urgent unmet clinical need.

Language: Английский

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Emerging Exosomes and Exosomal MiRNAs in Spinal Cord Injury

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: July 9, 2021

Acute spinal cord injury (SCI) is a serious traumatic event to the with considerable morbidity and mortality. This leads short- long-term variations in cord, can have effect on patient's sensory, motor, or autonomic functions. Due complicated pathological process of SCI, there currently no successful clinical treatment strategy. Exosomes, extracellular vesicles (EVs) double-layer membrane structure 30-150 nm diameter, recently been considered as critical mediators for communication between cells tissues by transferring proteins, lipids, nucleic acids. Further studies verified that exosomes participate pathophysiological several diseases, including cancer, neurodegenerative cardiovascular could significant impact their treatment. As natural carriers biologically active cargos, emerged SCI. In this review article, we critically discuss functions intracellular potential treatments SCI provide an outlook future research.

Language: Английский

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The role of damage associated molecular pattern molecules (DAMPs) and permeability of the blood-brain barrier in depression and neuroinflammation

Journal of Neuroimmunology, Journal Year: 2022, Volume and Issue: 371, P. 577951 - 577951

Published: Aug. 17, 2022

Language: Английский

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Military traumatic brain injury: a challenge straddling neurology and psychiatry

Military Medical Research, Journal Year: 2022, Volume and Issue: 9(1)

Published: Jan. 6, 2022

Military psychiatry, a new subcategory of has become an invaluable, intangible effect the war. In this review, we begin by examining related military research, summarizing epidemiological data, neuropathology, and research achievements diagnosis treatment technology, discussing its comorbidity sequelae. To date, advances in neuroimaging molecular biology have greatly boosted studies on traumatic brain injury (TBI). particular, terms pathophysiological mechanisms, several preclinical identified abnormal protein accumulation, blood-brain barrier damage, metabolism abnormalities involved development TBI. As important concept field TBI is based organic injury, which largely different from many other mental disorders. Therefore, both neuropathic psychopathic, emerging challenge at intersection neurology psychiatry.

Language: Английский

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