Fluid biomarkers of the neurovascular unit in cerebrovascular disease and vascular cognitive disorders: A systematic review and meta-analysis

Cerebral Circulation - Cognition and Behavior, Год журнала: 2024, Номер 6, С. 100216 - 100216

Опубликована: Янв. 1, 2024

The disruption of the neurovascular unit (NVU), which maintains integrity blood brain barrier (BBB), has been identified as a critical mechanism in development cerebrovascular and neurodegenerative disorders. However, understanding pathophysiological mechanisms linking NVU dysfunction to disorders is incomplete, reliable biomarkers measure are yet be established. This systematic review meta-analysis aimed identify associated with BBB large vessel disease, small disease (SVD) vascular cognitive (VCD). A literature search was conducted PubMed, EMBASE, Scopus PsychINFO related pathologies published until 20 November 2023. Studies that assayed one or more specific markers human serum plasma were included. Quality studies assessed using Newcastle-Ottawa Assessment Scale. Effects pooled methodological heterogeneity examined random effects model. total 117 included this review. Where study numbers allowed, analysed effect for VCD (1 biomarker; 5 studies) disorders, including stroke SVD (9 biomarkers; 27 while all remaining (n=17 77 through qualitative analysis. Results revealed cerebrospinal fluid/serum albumin quotient (Q-Alb) reliably differentiates patients from healthy controls (MD = 2.77; 95% CI 1.97 3.57; p <0.0001) commonly measured endothelial (VEGF, VCAM-1, ICAM-1, vWF E-selectin) neuronal injury (NfL) significantly elevated pathologies. assessment non-meta-analysed NSE, NfL, vWF, lipocalin-2, MMP-2 MMP-9 levels upregulated VCD, although these findings not consistently replicated. identifies several promising require further validation. panel representing multiple pathways may offer greater discriminative power distinguishing possible VCD.

Язык: Английский

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Gliovascular transcriptional perturbations in Alzheimer’s disease reveal molecular mechanisms of blood brain barrier dysfunction

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Июнь 20, 2024

Abstract To uncover molecular changes underlying blood-brain-barrier dysfunction in Alzheimer’s disease, we performed single nucleus RNA sequencing 24 disease and control brains focused on vascular astrocyte clusters as main cell types of gliovascular-unit. The majority the transcriptional were pericytes. Of targets predicted to interact with astrocytic ligands, SMAD3 , upregulated pericytes, has highest number ligands including VEGFA downregulated astrocytes. We validated these findings external datasets comprising 4,730 pericyte 150,664 nuclei. Blood levels are associated disease-related neuroimaging outcomes. determined inverse relationships between pericytic human iPSC zebrafish models. Here, detect vast transcriptome at gliovascular-unit, prioritize perturbed -astrocytic interactions, validate cross-species models provide a mechanism disintegrity disease.

Язык: Английский

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STING immune activation of microglia aggravating neurovascular unit damage in diabetic retinopathy

Free Radical Biology and Medicine, Год журнала: 2025, Номер 233, С. 86 - 101

Опубликована: Март 30, 2025

Язык: Английский

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The pathophysiological mechanisms underlying diabetic retinopathy

Frontiers in Cell and Developmental Biology, Год журнала: 2022, Номер 10

Опубликована: Авг. 30, 2022

Diabetic retinopathy (DR) is the most common complication of diabetes mellitus (DM), which can lead to visual impairment and even blindness in severe cases. DR generally considered be a microvascular disease but its pathogenesis still unclear. A large body evidence shows that development not determined by single factor rather multiple related mechanisms different degrees retinal damage patients. Therefore, this article briefly reviews pathophysiological changes DR, discusses occurrence resulting from factors such as oxidative stress, inflammation, neovascularization, neurodegeneration, neurovascular unit, gut microbiota, provide theoretical reference for new treatment strategies.

Язык: Английский

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Influence of Oxidative Stress and Inflammation on Nutritional Status and Neural Plasticity: New Perspectives on Post-Stroke Neurorehabilitative Outcome

Nutrients, Год журнала: 2022, Номер 15(1), С. 108 - 108

Опубликована: Дек. 26, 2022

Beyond brain deficits caused by strokes, the effectiveness of neurorehabilitation is strongly influenced baseline clinical features stroke patients, including a patient’s current nutritional status. Malnutrition, either as pre-stroke existing condition or occurring because ischemic injury, predisposes patients to poor rehabilitation outcomes. On other hand, proper status compliant with specific needs required process recovery plays key role in post-stroke rehabilitative outcome favoring neuroplasticity mechanisms. Oxidative stress and inflammation play stroke-associated malnutrition, well cascade events area, where damage leads neuronal death infarction, and, via cell-to-cell signaling, alteration processes underlying functional induced multidisciplinary treatment. Nutrition strategies based on food components oxidative anti-inflammatory properties may help reverse stop malnutrition be prerequisite for supporting ability plasticity result satisfactory patients. To expand recommendations recovery, studies considering evolution changes over time are required. The assessment must included routine tool settings integrated care stroke-patients.

Язык: Английский

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The role of population-level preventive care for brain health in ageing

The Lancet Healthy Longevity, Год журнала: 2023, Номер 4(6), С. e274 - e283

Опубликована: Май 16, 2023

Over the past several decades, a worldwide demographic transition has led to an increasing number of older adults with chronic neurological conditions. These conditions, which have profound effect on cognitive function and physical ability adults, also long preclinical phase. This feature provides unique opportunity implement preventive measures for high-risk groups population as whole, therefore reduce burden diseases. The concept brain health emerged overarching theme define overall independently underlying pathophysiological processes. We review from ageing care perspectives, discuss mechanisms underpinning ageing, highlight interplay various forces resulting in deviation towards disease, provide overview strategies promote life-course approach.

Язык: Английский

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Three-photon excited fluorescence imaging in neuroscience: From principles to applications

Frontiers in Neuroscience, Год журнала: 2023, Номер 17

Опубликована: Фев. 20, 2023

The development of three-photon microscopy (3PM) has greatly expanded the capability imaging deep within biological tissues, enabling neuroscientists to visualize structure and activity neuronal populations with greater depth than two-photon imaging. In this review, we outline history physical principles 3PM technology. We cover current techniques for improving performance 3PM. Furthermore, summarize applications various brain regions species. Finally, discuss future neuroscience.

Язык: Английский

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Current status and advances to improving drug delivery in diffuse intrinsic pontine glioma

Journal of Controlled Release, Год журнала: 2024, Номер 370, С. 835 - 865

Опубликована: Май 20, 2024

Diffuse midline glioma (DMG), including tumors diagnosed in the brainstem (diffuse intrinsic pontine - DIPG), is primary cause of brain tumor-related death pediatric patients. DIPG characterized by a median survival <12 months from diagnosis, harboring worst 5-year rate any cancer. Corticosteroids and radiation are mainstay therapy; however, they only provide transient relief devastating neurological symptoms. Numerous therapies have been investigated for DIPG, but majority unsuccessful demonstrating benefit beyond alone. Although many barriers hinder drug delivery one most significant challenges blood-brain barrier (BBB). Therapeutic compounds must possess specific properties to enable efficient passage across BBB. In cancer, BBB referred as tumor (BBTB), where disrupt structure function BBB, which may opportunities delivery. However, biological characteristics brainstem's BBB/BBTB, both under normal physiological conditions response poorly understood, further complicates treatment. Better characterization changes that occur BBB/BBTB patients essential, this informs future treatment strategies. Many novel technologies bypass or convection enhanced delivery, focused ultrasound, nanoparticle-mediated intranasal all yet be clinically established DIPG. Herein, we review what known about discuss current status, limitations, advances conventional treatments improving

Язык: Английский

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Microvascular destabilization and intricated network of the cytokines in diabetic retinopathy: from the perspective of cellular and molecular components

Cell & Bioscience, Год журнала: 2024, Номер 14(1)

Опубликована: Июнь 27, 2024

Microvascular destabilization is the primary cause of inner blood-retinal barrier (iBRB) breakdown and increased vascular leakage in diabetic retinopathy (DR). results from combinational effects levels growth factors cytokines, involvement inflammation, changed cell-to-cell interactions, especially loss endothelial cells pericytes, due to hyperglycemia hypoxia. As manifestation microvascular destabilization, fluid transports via paracellular transcellular routes increase disruption intercellular junctional complexes and/or altered caveolar transport across retinal endothelium. With diabetes progression, functional structural changes iBRB components, including cellular noncellular further facilitate aggravate resulting macular edema, neuroretinal damage dysfunction neurovascular unit (iNVU). Although there have been considerable recent advances towards a better understanding complex molecular network underlying some still remain be fully elucidated. Recent data indicate that targeting intricate signaling pathways may allow against destabilization. Therefore, efforts made clarify mechanisms are involved DR. In this review, we discuss: (1) brief introduction DR destabilization; (2) components iNVU, iBRB; (3) matrix contacts maintain stabilization, glycocalyx, basement membrane, various cell-cell interactions; (4) mediated cell death; (5) cytokines as well This comprehensive review aimed provide insights for by key molecules or specific cells, thus restoring function structure treat

Язык: Английский

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Updated Understanding of the Glial-Vascular Unit in Central Nervous System Disorders

Neuroscience Bulletin, Год журнала: 2022, Номер 39(3), С. 503 - 518

Опубликована: Ноя. 14, 2022

Язык: Английский

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