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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Dysbiosis of the gut microbiota and its effect on α-synuclein and prion protein misfolding: consequences for neurodegeneration

Frontiers in Cellular and Infection Microbiology, Год журнала: 2024, Номер 14

Опубликована: Фев. 16, 2024

Abnormal behavior of α-synuclein and prion proteins is the hallmark Parkinson’s disease (PD) illnesses, respectively, being complex neurological disorders. A primary cause protein aggregation, brain injury, cognitive loss in illnesses misfolding normal cellular (PrP C ) into an infectious form Sc ). Aggregation causes disruptions processes (PD), leading to dopamine-producing neurons motor symptoms. Alteration composition or activity gut microbes may weaken intestinal barrier make it possible for prions go from brain. The gut-brain axis linked neuroinflammation; metabolites produced by microbiota affect aggregation α-synuclein, regulate inflammation immunological responses, influence course neurotoxicity proteins, even if their targets are distinct proteins. This thorough analysis explores interactions that exist between neurodegenerative particularly involvement microbiota, a collection bacteria, archaea, fungi, viruses etc., various becoming increasingly recognized. microbiome influences neuroinflammation, neurotransmitter synthesis, mitochondrial function, integrity through axis, which contributes development progression disease. review delves molecular mechanisms underlie these relationships, emphasizing effects microbial such as bacterial lipopolysaccharides (LPS), short-chain fatty acids (SCFAs) regulating functioning. Additionally, looks at how environmental dietary decisions whether they could be risk factors illnesses. study concludes highlighting critical role plays It also provides promising direction future research treatment approaches. People afflicted difficult ailments find hope new preventive therapeutic approaches diseases better understood.

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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Targeting Neuroinflammation by Pharmacologic Downregulation of Inflammatory Pathways Is Neuroprotective in Protein Misfolding Disorders

ACS Chemical Neuroscience, Год журнала: 2024, Номер 15(7), С. 1533 - 1547

Опубликована: Март 20, 2024

Neuroinflammation plays a crucial role in the development of neurodegenerative protein misfolding disorders. This category progressive diseases includes, but is not limited to, Alzheimer's disease, Parkinson's and prion diseases. Shared pathogenesis involves accumulation misfolded proteins, chronic neuroinflammation, synaptic dysfunction, ultimately leading to irreversible neuronal loss, measurable cognitive deficits, death. Presently, there are few no effective treatments halt advancement We hypothesized that directly targeting neuroinflammation by downregulating transcription factor, NF-κB, inflammasome protein, NLRP3, would be neuroprotective. To achieve this, we used cocktail RNA therapeutics (SB_NI_112) shown brain-penetrant, nontoxic, inhibitors both NF-κB NLRP3. utilized mouse-adapted strain as model for assess aggregation glial inflammation, lifespan. Prion-diseased mice were treated either intraperitoneally or intranasally with SB_NI_112. Behavioral deficits significantly protected this combination NLRP3 downregulators. Treatment reduced against prevented spongiotic change, rescued lengthened lifespan prion-diseased mice. have identified systemic pharmacologic downregulates prevents death, slows progression Though mouse models do always predict human patient success study was due sample size number dosing methods utilized, these findings serve proof principle continued translation therapeutic SB_NI_112 disease other Based on murine model, will continue testing variety models, including disease.

Язык: Английский

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Utilization of nanotechnology to surmount the blood-brain barrier in disorders of the central nervous system

Materials Today Bio, Год журнала: 2025, Номер 31, С. 101457 - 101457

Опубликована: Янв. 5, 2025

Central nervous system (CNS) diseases are a major cause of disability and death worldwide. Due to the blood-brain barrier (BBB), drug delivery for CNS is extremely challenging. Nano-delivery systems can overcome limitations BBB deliver drugs CNS, improve ability target brain provide potential therapeutic methods diseases. At same time, choice different (bypassing or crossing BBB) further optimize effect nano-drug system. This article reviews nano-delivery way enters brain. Different kinds nanoparticles were discussed in depth.

Язык: Английский

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Semaglutide restores astrocyte–vascular interactions and blood–brain barrier integrity in a model of diet-induced metabolic syndrome

Diabetology & Metabolic Syndrome, Год журнала: 2025, Номер 17(1)

Опубликована: Янв. 4, 2025

Metabolic syndrome (MetS) is a metabolic disorder related to obesity and insulin resistance the primary determinant of development low-intensity chronic inflammation. This continuous inflammatory response culminates in neuroimmune-endocrine dysregulation responsible for abnormalities morbidities observed individuals with MetS. Events such as accumulation visceral adipose tissue, increased plasma concentrations free fatty acids, tissue hypoxia, sympathetic hyperactivity MetS may contribute activation innate immune response, which compromises cerebral microcirculation neurovascular unit, leading onset or progression neurodegenerative diseases. study aimed evaluate effects treatment GLP-1 receptor agonist (semaglutide) on unit (NVU) integrity. C57BL/6 mice were fed standard normolipidic diet high-fat (HFD) 24 weeks then treated 4 semaglutide (HFD SEMA) saline solution SAL). At end pharmacological treatment, biochemical analyses, immunohistochemistry analysis, intravital microscopy brain carried out quantify leukocyte–endothelium interactions assess structural capillary density, astrocyte coverage vessels microglial activation. We that SEMA attenuates diet-induced alterations HFD weeks. also reversed by reducing rarefaction interaction leukocytes postcapillary venules. The HFD-SEMA group exhibited improved vessels. However, did not reverse Semaglutide can microvascular restoring integrity unit. Adverse dietary stimuli compromise homeostasis semaglutide.

Язык: Английский

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Melatonin Regulates Glymphatic Function to Affect Cognitive Deficits, Behavioral Issues, and Blood–Brain Barrier Damage in Mice After Intracerebral Hemorrhage: Potential Links to Circadian Rhythms

CNS Neuroscience & Therapeutics, Год журнала: 2025, Номер 31(2)

Опубликована: Фев. 1, 2025

ABSTRACT Background Intracerebral hemorrhage (ICH) is a life‐threatening cerebrovascular disorder with no specific pharmacological treatment. ICH causes significant behavioral deficits and cognitive impairments. Recent research suggests that circadian rhythm regulation could be promising therapeutic strategy for ICH. Melatonin has been shown to alleviate glymphatic system (GS) dysfunction by regulating rhythms, thereby improving depressive‐like behaviors postoperative sleep disorders in mice. However, its application treatment mechanisms are not well understood. Methods models were created 8‐to‐10‐week‐old mice using collagenase injection. Circadian modulation was tested melatonin luzindole. Behavioral impairments assessed the modified neurological severity score, corner test, novel object recognition test. Brain water content measured dry/wet weight method, cerebral perfusion blood flow measurements. GS function evaluated RITC‐dextran Evans blue assays. Immunofluorescence western blotting used analyze BBB permeability. Results restored transport after ICH, promoting hematoma edema absorption, reducing damage, outcomes. luzindole partially blocked these benefits reversed neuroprotective effects. Conclusion affect function, permeability, cognitive‐behavioral outcomes The underlying mechanism may involve of rhythms.

Язык: Английский

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Extracellular vesicles as precision therapeutics for psychiatric conditions: targeting interactions among neuronal, glial, and immune networks

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Апрель 8, 2025

The critical role of the immune system in brain function and dysfunction is well recognized, yet development therapies for psychiatric diseases has been slow due to concerns about iatrogenic deficiencies. These are emphasized by lack objective diagnostic tools psychiatry. A promise resolve this conundrum lies exploitation extracellular vesicles (EVs) that physiologically produced or can be synthetized. EVs regulate recipient cell functions offer potential EVs-based therapies. Intranasal administration enables targeting specific regions functions, thereby facilitating design precise treatments diseases. such requires navigating four dynamically interacting networks: neuronal, glial, immune, EVs. networks profoundly influenced fluid distribution. They crucial homeostasis, cellular intercellular communication. Fluid abnormalities, like edema altered cerebrospinal (CSF) dynamics, disrupt these networks, negatively impacting health. deeper understanding above-mentioned vital creating biomarker panels identify distinct patient subsets with similar neuro-behavioral symptoms. Testing functional pathways biomarkers could lead new therapeutic tools. Regulatory approval will depend on robust preclinical data reflecting progress interdisciplinary areas, which pave way innovative treatments. Highly collaborative teams needed achieve ambitious goals.

Язык: Английский

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Hippocampus under Pressure: Molecular Mechanisms of Development of Cognitive Impairments in SHR Rats

Biochemistry (Moscow), Год журнала: 2024, Номер 89(4), С. 711 - 725

Опубликована: Апрель 1, 2024

Язык: Английский

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The Role of Glial Cells in Neurobiology and Prion Neuropathology

Cells, Год журнала: 2024, Номер 13(10), С. 832 - 832

Опубликована: Май 14, 2024

Prion diseases are rare and neurodegenerative that characterized by the misfolding infectious spread of prion protein in brain, causing progressive irreversible neuronal loss associated clinical behavioral manifestations humans animals, ultimately leading to death. The brain has a complex network neurons glial cells whose crosstalk is critical for function homeostasis. Although it established infection necessary disease occur, debate remains field as role played cells, namely astrocytes microglia, whether these beneficial host or further accelerate disease. Here, we review current literature assessing morphologies between two cell types, prion-infected brain.

Язык: Английский

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