Blood–Brain Barrier Disruption and Its Involvement in Neurodevelopmental and Neurodegenerative Disorders

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(23), С. 15271 - 15271

Опубликована: Дек. 3, 2022

The blood–brain barrier (BBB) is a highly specialized and dynamic compartment which regulates the uptake of molecules solutes from blood. relevance maintenance healthy BBB underpinning disease prevention as well main pathomechanisms affecting function will be detailed in this review. Barrier disruption common aspect both neurodegenerative diseases, such amyotrophic lateral sclerosis, neurodevelopmental including autism spectrum disorders. Throughout review, conditions altering during earliest latest stages life discussed, revealing factors involved. Due to barrier’s role protecting brain exogenous components xenobiotics, drug delivery across challenging. Potential therapies based on properties molecular Trojan horses, among others, reviewed, innovative treatments stem cell therapies. Additionally, due microbiome influence normal brain, microflora modulation strategies discussed. Finally, future research directions are highlighted address current gaps literature, emphasizing idea that for pathologies exist.

Язык: Английский

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In vivo methods for imaging blood–brain barrier function and dysfunction

European Journal of Nuclear Medicine and Molecular Imaging, Год журнала: 2022, Номер 50(4), С. 1051 - 1083

Опубликована: Ноя. 28, 2022

Abstract The blood–brain barrier (BBB) is the interface between central nervous system and systemic circulation. It tightly regulates what enters removed from brain parenchyma fundamental in maintaining homeostasis. Increasingly, BBB recognised as having a significant role numerous neurological disorders, ranging acute disorders (traumatic injury, stroke, seizures) to chronic neurodegeneration (Alzheimer’s disease, vascular dementia, small vessel disease). Numerous approaches have been developed study vitro, vivo, ex vivo. complex multicellular structure effects of disease are difficult recreate accurately functional aspects cannot be easily studied As such, value vivo methods intact overstated. This review discusses function how these affected diseases. then depth several established novel for imaging with focus on MRI, nuclear imaging, high-resolution intravital fluorescence microscopy.

Язык: Английский

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Cell-Membrane-Coated Nanoparticles for Targeted Drug Delivery to the Brain for the Treatment of Neurological Diseases

Pharmaceutics, Год журнала: 2023, Номер 15(2), С. 621 - 621

Опубликована: Фев. 13, 2023

Neurological diseases (NDs) are a significant cause of disability and death in the global population. However, effective treatments still need to be improved for most NDs. In recent years, cell-membrane-coated nanoparticles (CMCNPs) as drug-targeting delivery systems have become research hotspot. Such membrane-derived, nano drug-delivery system not only contributes avoiding immune clearance but also endows (NPs) with various cellular functional mimicries. This review article first provides an overview function mechanism single/hybrid cell-membrane-derived NPs. Then, we highlight application safety CMCNPs Finally, discuss challenges opportunities field.

Язык: Английский

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Imaging blood-brain barrier dysfunction: A state-of-the-art review from a clinical perspective

Frontiers in Aging Neuroscience, Год журнала: 2023, Номер 15

Опубликована: Апрель 17, 2023

The blood-brain barrier (BBB) consists of specialized cells that tightly regulate the in- and outflow molecules from blood to brain parenchyma, protecting brain’s microenvironment. If one BBB components starts fail, its dysfunction can lead a cascade neuroinflammatory events leading neuronal degeneration. Preliminary imaging findings suggest could serve as an early diagnostic prognostic biomarker for number neurological diseases. This review aims provide clinicians with overview emerging field in humans by answering three key questions: (1. Disease) In which diseases be useful? (2. Device) What are currently available methods evaluating integrity? And (3. Distribution) what is potential different environments, particularly resource limited settings? We conclude further advances needed, such validation, standardization implementation readily available, low-cost non-contrast techniques, useful clinical both resource-limited well-resourced settings.

Язык: Английский

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Fibrin promotes oxidative stress and neuronal loss in traumatic brain injury via innate immune activation

Journal of Neuroinflammation, Год журнала: 2024, Номер 21(1)

Опубликована: Апрель 15, 2024

Abstract Background Traumatic brain injury (TBI) causes significant blood-brain barrier (BBB) breakdown, resulting in the extravasation of blood proteins into brain. The impact proteins, especially fibrinogen, on inflammation and neurodegeneration post-TBI is not fully understood, highlighting a critical gap our comprehension TBI pathology its connection to innate immune activation. Methods We combined vascular casting with 3D imaging solvent-cleared organs (uDISCO) study spatial distribution coagulation protein fibrinogen large, intact volumes assessed temporal regulation fibrin(ogen) deposition by immunohistochemistry murine model TBI. Fibrin(ogen) cell markers were co-localized mouse human brains after role using unbiased transcriptomics, flow cytometry for neuronal Fgg γ390–396A knock-in mice, which express mutant that retains normal clotting function, but lacks γ390–396 binding motif CD11b/CD18 integrin receptor. Results show cerebral deposits associated activated cells both Genetic elimination fibrin-CD11b interaction reduced peripheral monocyte recruitment activation inflammatory reactive oxygen species (ROS) gene pathways microglia macrophages Blockade was also protective from oxidative stress damage cortical loss Conclusions These data suggest regulator Abrogating post-injury neuroinflammation selective blockade fibrin’s functions may have implications long-term neurologic recovery following trauma.

Язык: Английский

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Neuron-targeted liposomal coenzyme Q10 attenuates neuronal ferroptosis after subarachnoid hemorrhage by activating the ferroptosis suppressor protein 1/coenzyme Q10 system

Acta Biomaterialia, Год журнала: 2024, Номер 179, С. 325 - 339

Опубликована: Март 30, 2024

Язык: Английский

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Cerebral Glucose Metabolism following TBI: Changes in Plasma Glucose, Glucose Transport and Alternative Pathways of Glycolysis—A Translational Narrative Review

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(5), С. 2513 - 2513

Опубликована: Фев. 21, 2024

Traumatic brain injury (TBI) is a major public health concern with significant consequences across various domains. Following the primary event, secondary injuries compound outcome after TBI, disrupted glucose metabolism emerging as relevant factor. This narrative review summarises existing literature on post-TBI alterations in metabolism. After undergoes dynamic changes transport, including transporters and kinetics, disruptions blood-brain barrier (BBB). In addition, cerebral transitions from phase of hyperglycolysis to hypometabolism, upregulation alternative pathways glycolysis. Future research should further explore optimal, possibly personalised, glycaemic control targets TBI patients, GLP-1 analogues promising therapeutic candidates. Furthermore, more fundamental understanding activation pathways, such polyol lactate pathway, could hold key improving outcomes following TBI.

Язык: Английский

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Fluid and Electrolyte Disorders in Traumatic Brain Injury: Clinical Implications and Management Strategies

Journal of Clinical Medicine, Год журнала: 2025, Номер 14(3), С. 756 - 756

Опубликована: Янв. 24, 2025

Traumatic brain injuries (TBIs) cause direct central nervous system injury. The presentation depends on the location, type, and severity of Additional injury may develop secondary to compression, disruption cerebral perfusion, changes in sodium levels, resulting either cellular edema or dehydration. Plasma osmolality (Posm) is a critical parameter influenced by solute concentrations, including sodium, glucose, urea, relevant concern when considering levels these patients. While Posm can be calculated using standard formula, measurements via osmometry offer better accuracy. It essential differentiate between tonicity; latter refers specifically effective solutes that drive water movement extracellular fluid. Sodium its anions are solutes, whereas urea glucose have variable effects due their permeability insulin dependence. Following TBI, dysregulation osmoregulation occur affect neurological outcomes. Osmoreceptors regulate arginine vasopressin secretion response with chloride mannitol being potent stimuli. regulation plasma osmolality, typically maintained within ±5% 280–295 mOsm/kg H2O range, crucial for homeostasis relies antidiuresis thirst mechanisms. This review narrative underscores complexities context TBIs clinical implications, particularly concerning development conditions such as diabetes insipidus, syndrome inappropriate antidiuretic hormone secretion, abnormal thirst.

Язык: Английский

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High-altitude hypoxia aggravated neurological deficits in mice induced by traumatic brain injury via BACH1 mediating astrocytic ferroptosis

Cell Death Discovery, Год журнала: 2025, Номер 11(1)

Опубликована: Фев. 5, 2025

Abstract Traumatic brain injury (TBI) is one of the leading causes disability and mortality, which was classified as low-altitude TBI high-altitude TBI. A large amount literature shows that associated with more severe neurological impairments higher mortality rates compared to TBI, due special environment hypoxia. However, role hypoxia in pathogenesis remains unclear. In order deeply investigate this scientific issue, we constructed a hypoxic model at different altitudes used animal behavioral assessments (Modified severity score, rotarod test, elevated plus maze test) well histopathological analyses (brain gross specimens, water content, Evans blue inducible factor-1α, Hematoxylin-Eosin staining ROS detection) reveal its underlying principles characteristics. We found altitude, TBI-induced deficits were changes significant. Single-nuclear RNA sequencing subsequently employed further differential gene expression profiles significant increase ferroptosis astrocytes cases those Analyzing transcription factors depth, Bach1 plays crucial regulating key molecules induce following Down-regulation can effectively alleviate mice. conclusion, may significantly enhance aggravate by up-regulating expression. Our study provides theoretical foundation for understanding mechanism targeted intervention therapy.

Язык: Английский

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Much More than Nutrients: The Protective Effects of Nutraceuticals on the Blood–Brain Barrier in Diseases

Nutrients, Год журнала: 2025, Номер 17(5), С. 766 - 766

Опубликована: Фев. 21, 2025

The dysfunction of the blood-brain barrier (BBB) is well described in several diseases, and considered a pathological factor many neurological disorders. This review summarizes most important groups natural compounds, including alkaloids, flavonoids, anthocyanidines, carotenoids, lipids, vitamins that were investigated for their potential protective effects on brain endothelium. penetration these compounds interaction with BBB efflux transporters solute carriers are discussed. cerebrovascular endothelium therapeutic target diseases. In preclinical studies modeling systemic central nervous system nutraceuticals exerted beneficial BBB. vivo, they decreased permeability, edema, astrocyte swelling, morphological changes vessel structure basal lamina. At level endothelial cells, increased cell survival apoptosis. From general functions, angiogenesis levels vasodilating agents demonstrated. elevated integrity by tightened intercellular junctions, expression activity transporters, such as pumps, carriers, metabolic enzymes, shown. Nutraceuticals enhanced antioxidative defense anti-inflammatory at signaling mediating stability activation WNT, PI3K-AKT, NRF2 pathways, inhibition MAPK, JNK, ERK, NF-κB pathways. represent valuable source new potentially molecules to treat diseases protecting

Язык: Английский

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