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

Journal of Clinical Medicine, Год журнала: 2025, Номер 14(2), С. 386 - 386

Опубликована: Янв. 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

Язык: Английский

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Prenatal Alcohol Consumption Alters Protein Fingerprint in Umbilical Cord Blood Serum and Induces Brain Microvascular Endothelial Cell Dysfunction

Journal of Neurochemistry, Год журнала: 2025, Номер 169(2)

Опубликована: Фев. 1, 2025

Consumption of alcoholic beverages during pregnancy is directly related to the establishment fetal alcohol spectrum disorders (FASD), which includes craniofacial changes, body growth restriction, and neurodevelopment impairments. Proper functioning central nervous system (CNS) depends on blood-brain barrier (BBB) development, formed by interactions vascular endothelial cells, pericytes, astrocytes, basal lamina. Gestational exposure ethanol has been demonstrated impair CNS development; however, little known about modulation blood circulating factors impacts human developing BBB. Here we investigated prevalence consumption found that 27% pregnant women reported consumption, mainly in first trimester. Control alcohol-exposed newborns showed no differences weight, length, appearance, pulse, grimace, activity, respiration (APGAR) score at birth. In vitro, cultivated brain microcapillary cells (HBMEC) treated with umbilical cord serum (UCBS) from control (S-Control) or ethanol-exposed ones (S-Ethanol). S-Ethanol treatment induced 68% 38% decreases protein levels ZO-1 (tight junction) GLUT-1 (glucose transporter type-1), respectively, increased monolayer permeability, migratory potential impairment, changes angiogenesis-related secreted proteins profile, compared S-Control treatments. UCBS proteomics revealed a total 392 proteins, 10 exclusively S-Ethanol, mostly innate adaptive immunity tissue injury response. These results suggest gestational contributes altered profiles triggering BBB endothelial.

Язык: Английский

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Δ9-Tetrahydrocannabinol induces blood-brain barrier disruption: involving the activation of CB1R and oxidative stress

Neuropharmacology, Год журнала: 2025, Номер 270, С. 110366 - 110366

Опубликована: Фев. 15, 2025

Язык: Английский

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Polymer-based nanocarriers to transport therapeutic biomacromolecules across the blood-brain barrier

Acta Biomaterialia, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Therapeutic biomacromolecules such as genetic material, antibodies, growth factors and enzymes represent a novel therapeutic alternative for neurological diseases disorders. In comparison to traditional therapeutics, which are mainly based on small molecular weight drugs that address the symptoms of these disorders, can reduce undesired side effects target specific pathological pathways, thus paving way towards personalized medicine. However, undergo degradation/denaturation processes in physiological environment show poor capacity cross blood-brain barrier (BBB). Consequently, they rarely reach central nervous system (CNS) their active form. Herein, we critically overview several polymeric nanocarriers protect deliver across BBB. Polymeric first categorized architecture (biodegradable solid nanoparticles, nanogels, dendrimers, self-assembled nanoparticles), ultimately determines physico-chemical properties function. The available formulations then thoroughly analyzed, placing particular attention those strategies ensure stability during encapsulation process promote passage BBB by controlling physical (e.g., mechanical properties, size, surface charge) chemical functional groups, targeting motifs) properties. Accordingly, this review gives unique perspective delivery BBB, representing concise, complete easy-to-follow guide, will be high interest chemists, material scientists, pharmacologists biologists. Besides, it also provides critical about limited clinical translation systems. STATEMENT OF SIGNIFICANCE: increasing incidence disorders is major health concern. use has been placed spotlight many investigations. reaching concentration levels restricted and, thus, represents main challenge when developing efficient therapies. provide discussion into system, highlighting potential future directions overcome current challenges.

Язык: Английский

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Mechanisms of receptor-mediated transcytosis at the blood-brain barrier

Journal of Controlled Release, Год журнала: 2025, Номер 381, С. 113595 - 113595

Опубликована: Март 6, 2025

In receptor-mediated transcytosis (RMT) of large therapeutics across the blood-brain barrier (BBB), construct - a macromolecule or larger carrier with therapeutic payload binds protein on brain capillary endothelial cells (BCEC), internalization and release into parenchyma. The construct's into, trafficking from, but also possible entrapment within BCEC are affected by its engineered properties whose optimization has helped derive insights transport mechanisms at BCEC. Furthermore, advances in multi-omics, as well large-scale screening directed evolution campaigns have identify new targets for RMT this perspective, I raise reflect some fundamental questions one can arrive comparing BBB-targeted constructs different target proteins. These concern underlying, transcytosis-promoting factors that constructs' appears to converge on, precise role proteins RMT, through which these may mediate trafficking, tentative criteria selection Based considerations propose several scenarios strategies interfere more efficient internalization, endosomal network toward abluminal membrane, from BCEC, both smaller macromolecules carriers.

Язык: Английский

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Ultrasonic head-mounted device spatiotemporal opening blood–brain barrier enhances the brain permeation of drugs for treatment of radiation-induced brain injury

International Journal of Pharmaceutics, Год журнала: 2025, Номер unknown, С. 125430 - 125430

Опубликована: Март 1, 2025

Язык: Английский

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Potential Roles of Natural Antioxidants in Modulating Neurodegenerative Disease Pathways

Molecular Neurobiology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 9, 2025

Язык: Английский

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Whispers in the Brain: Extracellular Vesicles in Neuropathology and the Diagnostic Alchemy of Neurological Diseases

European Journal of Neuroscience, Год журнала: 2025, Номер 61(8)

Опубликована: Апрель 1, 2025

ABSTRACT Extracellular vesicles (EVs) have emerged as pivotal mediators in neurological diseases, showcasing multifaceted potential roles ranging from pathogenesis to diagnosis. These nano‐sized membranous structures, released by various cell types including neurons, astrocytes, and microglia, encapsulate a diverse cargo of proteins, lipids, RNA species, even DNA fragments. In neuropathology, EVs contribute significantly intercellular communication within the central nervous system (CNS), influencing physiological or pathological cascades. Through transfer bioactive molecules, modulate neuroinflammation, neuronal survival, synaptic plasticity, propagation protein aggregates characteristic neurodegenerative disorders. Moreover, their presence biofluids such cerebrospinal fluid (CSF), blood, urine reflects pathophysiological state CNS, offering window into diagnosis, monitoring treatment diseases. Recent advancements EV isolation techniques, coupled with high‐throughput omics technologies, facilitated profiling cargo, enabling identification disease‐specific biomarkers high sensitivity specificity. This review explores intricate highlighting involvement Alzheimer's disease, Parkinson's multiple sclerosis, other Furthermore, it delves diagnostic EVs, discussing current challenges prospects harnessing EV‐derived for precision medicine neurology. Ultimately, understanding biology contexts promises transformative insights disease mechanisms therapeutic strategies, paving way innovative tools targeted interventions clinical practice.

Язык: Английский

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Understanding central nervous system fluid networks: Historical perspectives and a revised model for clinical neurofluid imaging.

NMR in Biomedicine, Год журнала: 2024, Номер 37(9), С. e5149 - e5149

Опубликована: Сен. 1, 2024

The central nervous system (CNS) lacks traditionally defined lymphatic vasculature. However, CNS tissues and barriers compartmentalize the brain, spinal cord, adjacent spaces, facilitating transmittal of fluids, metabolic wastes, immune cells, vital signals, while more conventional pathways in meninges, cervicofacial paraspinal regions transmit efflux fluid molecules to peripheral lymph nodes. Thus, a unique highly organized circulation network encompassing intraparenchymal, subarachnoid, dural, extradural segments functions unison maintain homeostasis. Pathways involved this have been under investigation for centuries continue be source considerable interest debate. Modern imaging microscopy technologies led important breakthroughs pertaining various elements circuitry exchange over past decade, thus enhancing knowledge on mechanisms mammalian maintenance disease. Yet, better understand precise anatomical routes, physiology clinical significance these pathways, potential therapeutic targets humans, conduits, flow-regulating factors, tissue effects must analyzed systematically global manner persons across age, demographical disease states. Here, we illustrate system-wide nature intermixing networks, summarize historical studies, discuss physiological similarities differences that are relevant translation evidence from mice humans. We also review Cushing's classical model cerebrospinal flow present new framework "third circulation" emphasizes previously unexplained complexities Finally, future directions field, including emerging theranostic techniques MRI studies required

Язык: Английский

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Laser interstitial thermal therapy (LITT) for pediatric low-grade glioma—case presentations and lessons learned

Child s Nervous System, Год журнала: 2024, Номер 40(10), С. 3119 - 3127

Опубликована: Май 4, 2024

The surgical treatment of brain tumors has developed over time, offering customized strategies for patients and their specific lesions. One the most recent advances in pediatric neuro-oncological surgery is laser interstitial thermal therapy (LITT). However, its effectiveness indications are still being evaluated. aim this work to review current literature on LITT low-grade gliomas (pLGG) evaluate our initial results context.

Язык: Английский

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