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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Breaking barriers: exploring mechanisms behind opening the blood–brain barrier

Fluids and Barriers of the CNS, Год журнала: 2023, Номер 20(1)

Опубликована: Ноя. 28, 2023

The blood-brain barrier (BBB) is a selectively permeable membrane that separates the bloodstream from brain. While useful for protecting neural tissue harmful substances, brain-related diseases are difficult to treat due this barrier, as it also limits efficacy of drug delivery. To address this, promising new approaches enhancing delivery based on disrupting BBB using physical means, including optical/photothermal therapy, electrical stimulation, and acoustic/mechanical stimulation. These mechanisms can temporarily locally open BBB, allowing drugs other substances enter. Focused ultrasound particularly promising, with ability focus energies targeted, deep-brain regions. In review, we examine recent advances in temporary disruption, describing their underlying well evaluating utility these regard potential risks limitations. methods have demonstrated safety, comparative efficacy, practicality clinical use remain an ongoing topic research.

Язык: Английский

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Reconsidering the role of blood-brain barrier in Alzheimer’s disease: From delivery to target

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

Опубликована: Фев. 16, 2023

The existence of a selective blood-brain barrier (BBB) and neurovascular coupling are two unique central nervous system vasculature features that result in an intimate relationship between neurons, glia, blood vessels. This leads to significant pathophysiological overlap neurodegenerative cerebrovascular diseases. Alzheimer's disease (AD) is the most prevalent whose pathogenesis still be unveiled but has mostly been explored under light amyloid-cascade hypothesis. Either as trigger, bystander, or consequence neurodegeneration, vascular dysfunction early component pathological conundrum AD. anatomical functional substrate this degeneration BBB, dynamic semi-permeable interface consistently shown defective. Several molecular genetic changes have demonstrated mediate BBB disruption isoform ε4 Apolipoprotein E at same time strongest risk factor for AD known promoter dysfunction. Low-density lipoprotein receptor-related protein 1 (LRP-1), P-glycoprotein, receptor advanced glycation end products (RAGE) examples transporters implicated its due their role trafficking amyloid-β. currently devoid strategies change natural course burdening illness. unsuccess may partly explained by our misunderstanding inability develop drugs effectively delivered brain. represent therapeutic opportunity target itself vehicle. In review, we aim explore including background detail how it can targeted future research.

Язык: Английский

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Translating ultrasound-mediated drug delivery technologies for CNS applications

Advanced Drug Delivery Reviews, Год журнала: 2024, Номер 208, С. 115274 - 115274

Опубликована: Март 6, 2024

Ultrasound enhances drug delivery into the central nervous system (CNS) by opening barriers between blood and CNS triggering release of drugs from carriers. A key challenge in translating setups vitro to vivo settings is achieving equivalent acoustic energy delivery. Multiple devices have now been demonstrated focus ultrasound brain, with concepts emerging also target spinal cord. Clinical trials date used facilitate blood–brain barrier. While most focused on feasibility safety considerations, therapeutic benefits are beginning emerge. To advance translation these technologies for applications, researchers should standardise exposure protocol fine-tune parameters. Computational modelling be increasingly as a core component develop both delivering accurate reproducible CNS. This field holds promise transformative advancements management pharmacological treatment complex challenging disorders.

Язык: Английский

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Breaking Barriers in Huntington’s Disease Therapy: Focused Ultrasound for Targeted Drug Delivery

Neurochemical Research, Год журнала: 2025, Номер 50(1)

Опубликована: Янв. 3, 2025

Abstract Huntington’s disease (HD) is a progressive neurodegenerative resulting from mutation in the huntingtin (HTT) gene and characterized by motor dysfunction, cognitive decline, psychiatric disturbances. Currently, no disease-modifying treatments are available. Recent research has developed therapeutic agents that may have potential to directly target pathology, such as silencing or clearing mutant protein. However, these limited their inability cross blood-brain barrier (BBB), preventing optimal effects. Although various techniques been explored overcome BBB, focused ultrasound (FUS) emerged promising non-invasive modality offering for targeted intervention diseases, including HD. Preclinical studies demonstrated safety efficacy of FUS delivering agents, siRNAs AAV vector-based therapy, significant reductions HTT expression improvements function HD mouse models. Furthermore, profile FUS-induced BBB opening established clinical trials on human patients diseases other than HD, showing adverse effects brain structure function. This review provides comprehensive overview current state connects existing evidence with its promise establishing therapies Graphical

Язык: Английский

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Focused Ultrasound as Targeted Therapy for Colorectal Cancer: A Comprehensive Review

Gastrointestinal Disorders, Год журнала: 2024, Номер 6(2), С. 380 - 401

Опубликована: Апрель 13, 2024

Traditional cancer treatments have not significantly improved the survival rates for individuals with colorectal cancer. As a result, there is dire need to explore novel treatment modalities that can target cancer-specific niches, transform cold tumors into hot ones, and disrupt tumor niche. Therapeutic focused ultrasound, recognized its capacity induce thermal mechanical impacts on tissue, potentially eliminate cells elicit body’s anticancer reaction by disrupting microenvironment. This article provides an overview of recent developments in employing therapeutic ultrasound (TFUS) enhance natural defenses against cancers. It also discusses studies examining utility TFUS treating patients research indicating potential stimulate response various vitro vivo models. Furthermore, it explores effects immune system highlights safety effectiveness managing cancer, providing relief from pain, improving rates. Given indications may bolster augment therapy clinical preclinical models, has emerge as pivotal tool settings.

Язык: Английский

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A sporadic Alzheimer's blood-brain barrier model for developing ultrasound-mediated delivery of Aducanumab and anti-Tau antibodies

Theranostics, Год журнала: 2022, Номер 12(16), С. 6826 - 6847

Опубликована: Янв. 1, 2022

Rationale:The blood-brain barrier (BBB) is a major impediment to therapeutic intracranial drug delivery for the treatment of neurodegenerative diseases, including Alzheimer's disease (AD).Focused ultrasound applied together with microbubbles (FUS +MB ) novel technique transiently open BBB and increase delivery.Evidence suggests that FUS safe, however, effects on human cells, especially in context AD, remain sparsely investigated.In addition, there currently are no cell platforms test -mediated delivery.Methods: Here we generated cells (induced brain endothelial-like (iBECs) astrocytes (iAstrocytes)) from apolipoprotein E gene allele E4 (APOE4, high sporadic AD risk) E3 (APOE3, lower carrying patient-derived induced pluripotent stem (iPSCs).We established mono-and co-culture models control investigate phenotype screen two potentially antibodies, an Aducanumab-analogue (Aduhelm TM ; anti-amyloid-β) anti-Tau antibody, RNF5.We then developed hydrogel-based 2.5D model as step towards more physiologically relevant platform.Results: When compared untreated RNF5 was significantly increased (up 1.73 fold), across Transwell-based following treatment.Our results also demonstrated safety indicated by minimal changes iBEC transcriptome well little or iAstrocyte viability inflammatory responses within first 24 h post .Furthermore, successful formation our (1.4 fold) .Conclusion: Our demonstrate robust reproducible approach utilize patient screening vitro.With such platform research previously not reported, it has potential identify -deliverable drugs cell-and patient-specific , accelerating use modality AD.

Язык: Английский

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Harnessing Ultrasound for Targeting Drug Delivery to the Brain and Breaching the Blood–Brain Tumour Barrier

Pharmaceutics, Год журнала: 2022, Номер 14(10), С. 2231 - 2231

Опубликована: Окт. 19, 2022

Despite significant advances in developing drugs to treat brain tumours, achieving therapeutic concentrations of the drug at tumour site remains a major challenge due presence blood–brain barrier (BBB). Several strategies have evolved enhance delivery chemotherapeutic agents tumours; however, most approaches several limitations which hinder their clinical utility. Promising studies indicate that ultrasound can penetrate skull target specific regions and transiently open BBB, safely reversibly, with high degree spatial temporal specificity. In this review, we initially describe basics ultrasound, then detail ultrasound-based mechanisms by improve therapy. We review pre-clinical findings from ultrasound-mediated BBB opening outline current devices technologies designed for purpose.

Язык: Английский

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Current clinical investigations of focused ultrasound blood-brain barrier disruption: A review

Neurotherapeutics, Год журнала: 2024, Номер 21(3), С. e00352 - e00352

Опубликована: Апрель 1, 2024

The blood-brain barrier (BBB) presents a formidable challenge in delivering therapeutic agents to the central nervous system. Ultrasound-mediated BBB disruption has emerged as promising non-invasive technique enhance drug delivery brain. This manuscript reviews fundamental principles of ultrasound-based techniques and their mechanisms action temporarily permeabilizing BBB. Clinical trials employing ultrasound for are discussed, summarizing diverse applications ranging from treatment neurodegenerative diseases targeted brain tumors. review also addresses safety considerations, outlining current understanding potential risks mitigation strategies associated with exposure, including real-time monitoring assessment efficacy. Among large number studies, significant successes highlighted thus providing perspective on future direction field.

Язык: Английский

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A comprehensive review of advanced focused ultrasound (FUS) microbubbles-mediated treatment of Alzheimer’s disease

Heliyon, Год журнала: 2024, Номер 10(18), С. e37533 - e37533

Опубликована: Сен. 1, 2024

Язык: Английский

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