Cellular and molecular mechanisms of the blood–brain barrier dysfunction in neurodegenerative diseases

Fluids and Barriers of the CNS, Journal Year: 2024, Volume and Issue: 21(1)

Published: July 19, 2024

Abstract Background Maintaining the structural and functional integrity of blood–brain barrier (BBB) is vital for neuronal equilibrium optimal brain function. Disruptions to BBB performance are implicated in pathology neurodegenerative diseases. Main body Early indicators multiple disorders humans animal models include impaired stability, regional cerebral blood flow shortfalls, vascular inflammation associated with dysfunction. Understanding cellular molecular mechanisms dysfunction crucial elucidating sustenance neural computations under pathological conditions developing treatments these This paper initially explores definition BBB, along signaling pathways regulating flow, inflammation. Subsequently, we review current insights into dynamics Alzheimer’s disease, Parkinson's amyotrophic lateral sclerosis, sclerosis. The concludes by proposing a unified mechanism whereby contributes disorders, highlights potential BBB-focused therapeutic strategies targets, outlines lessons learned future research directions. Conclusions breakdown significantly impacts development progression diseases, unraveling underlying elucidate how sustained devise approaches.

Language: Английский

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Aging, Neurodegenerative Disorders, and Cerebellum

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 1018 - 1018

Published: Jan. 13, 2024

An important part of the central nervous system (CNS), cerebellum is involved in motor control, learning, reflex adaptation, and cognition. Diminished cerebellar function results cognitive impairment observed patients with neurodegenerative disorders such as Alzheimer's disease (AD), vascular dementia (VD), Parkinson's (PD), Huntington's (HD), spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), Friedreich's ataxia (FRDA), multiple (MS), even during normal aging process. In most disorders, mainly occurs a result morphological changes over time, although early stages some AD, also serves compensatory function. Biological accompanied by circuits, which are predominantly control. Despite decades research, functional contributions underlying molecular mechanisms remain largely unknown. Therefore, this review will highlight cellular events that disrupted process development disorders. We believe deeper insights into pathophysiological be essential for design new effective strategies neuroprotection alleviation

Language: Английский

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Sex differences in the blood–brain barrier: Implications for mental health

Frontiers in Neuroendocrinology, Journal Year: 2022, Volume and Issue: 65, P. 100989 - 100989

Published: March 8, 2022

Prevalence of mental disorders, including major depressive disorder (MDD), bipolar (BD) and schizophrenia (SZ) are increasing at alarming rates in our societies. Growing evidence points toward sex differences these conditions, high treatment resistance support the need to consider novel biological mechanisms outside neuronal function gain mechanistic insights that could lead innovative therapies. Blood-brain barrier alterations have been reported MDD, BD SZ. Here, we provide an overview sex-specific immune, endocrine, vascular transcriptional-mediated changes affect neurovascular integrity possibly contribute pathogenesis disorders. We also identify pitfalls current literature highlight promising biomarkers. Better understanding how adaptations can health status is essential not only context SZ but cardiovascular diseases stroke which associated with higher prevalence conditions.

Language: Английский

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Sex, hormones and cerebrovascular function: from development to disorder

Fluids and Barriers of the CNS, Journal Year: 2024, Volume and Issue: 21(1)

Published: Jan. 4, 2024

Abstract Proper cerebrovascular development and neurogliovascular unit assembly are essential for brain growth function throughout life, ensuring the continuous supply of nutrients oxygen. This involves crucial events during pre- postnatal stages through key pathways, including vascular endothelial factor (VEGF) Wnt signaling. These pathways pivotal growth, expansion, blood–brain barrier (BBB) maturation. Interestingly, fetal neonatal formation coincides with early peak activity hypothalamic-pituitary-gonadal axis, supporting idea sex hormonal influence on barriergenesis. Sex dysregulation in has been implicated neurodevelopmental disorders highly sexually dimorphic features, such as autism spectrum disorder (ASD) attention-deficit/hyperactivity (ADHD). Both show higher prevalence men, varying symptoms between sexes, boys exhibiting more externalizing behaviors, aggressivity or hyperactivity, girls displaying internalizing anxiety, depression, attention disorders. Indeed, ASD ADHD linked to high prenatal testosterone exposure reduced aromatase expression, potentially explaining differences symptomatology. In line this, estrogen levels seem attenuate symptoms. At level, sex- region-specific variations cerebral blood flow perfusion have reported both conditions, indicating an impact gonadal hormones system, disrupting its ability respond neuronal demands. review aims provide overview existing knowledge concerning maturation, well onset Here, we explore concept hormone interactions BBB function, a particular focus modulation VEGF We outline how these may be involved underpinnings ADHD. Outstanding questions potential avenues future research highlighted, uncovering sex-specific physiological pathological aspects might lead innovative therapeutic approaches context ASD, beyond.

Language: Английский

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Vulnerability of the Hippocampus to Insults: Links to Blood–Brain Barrier Dysfunction

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 1991 - 1991

Published: Feb. 6, 2024

The hippocampus is a critical brain substrate for learning and memory; events that harm the can seriously impair mental behavioral functioning. Hippocampal pathophysiologies have been identified as potential causes effects of remarkably diverse array medical diseases, psychological disorders, environmental sources damage. It may be more vulnerable than other areas to insults are related these conditions. One purpose this review assess vulnerability most prevalent types in multiple biomedical domains (i.e., neuroactive pathogens, neurotoxins, neurological conditions, trauma, aging, neurodegenerative disease, acquired injury, health endocrine developmental disabilities, nutrition) evaluate whether affect first prominently compared loci. A second consider role hippocampal blood–brain barrier (BBB) breakdown either causing or worsening harmful each insult. Recent research suggests BBB fragile also prone disruption transport mechanisms act maintain internal milieu. Moreover, compromised could factor common many different insults. Our analysis indicates parts brain, developing interventions protect help prevent ameliorate on memory cognition.

Language: Английский

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Dysregulation of neural tube vascular development as an aetiological factor in autism spectrum disorder: Insights from valproic acid exposure

The Journal of Physiology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Abstract Autism spectrum disorder (ASD) is a prevalent neurodevelopmental condition affecting substantial number of children globally, characterized by diverse aetiologies, including genetic and environmental factors. Emerging research suggests that neurovascular dysregulation during development could significantly contribute to autism. This review synthesizes the potential role vascular abnormalities in pathogenesis ASD explores insights from studies on valproic acid (VPA) exposure neural tube development. VPA, widely used antiepileptic drug mood stabilizer, crosses placental barrier impacts developing fetal brain. Studies indicate VPA disrupts normal angiogenesis reducing expression levels endothelial growth factor A (VEGFA) its receptors, purinergic signalling, which are crucial for both Such disruptions may lead neuronal migration pathfinding, potentially contributing behavioural manifestations ASD. Thus despite relatively limited findings, improper vascularization appears be ASD, as also suggested studies. Integrating these insights, it hypothesized factors should considered aetiological analysis idiopathic image

Language: Английский

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Matching Assistive Technology, Telerehabilitation, and Virtual Reality to Promote Cognitive Rehabilitation and Communication Skills in Neurological Populations: A Perspective Proposal

Technologies, Journal Year: 2023, Volume and Issue: 11(2), P. 43 - 43

Published: March 16, 2023

Neurological populations (NP) commonly experience several impairments. Beside motor and sensorial delays, communication intellectual disabilities are included. The COVID-19 pandemic has suddenly exacerbated their clinical conditions due to lockdown, quarantine, social distancing preventive measures. Healthcare services unavailability negatively impacted NP conditions, partially mitigated by vaccine diffusion. One way overcome this issue is the use of technology-aided interventions for both assessment rehabilitative purposes. Assistive technology-based interventions, telerehabilitation, virtual reality setups have been widely adopted help individuals with neurological damages or injuries. Nevertheless, best our knowledge, matching (i.e., combination integration) rarely investigated. main objectives current position paper were (a) provide reader a perspective proposal on three aforementioned technological solutions, (b) outline concise background (c) argue effectiveness suitability technology-mediated programs, (d) postulate an integrative support cognitive rehabilitation including assistive technology, reality. Practical implications research practice critically discussed.

Language: Английский

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Astroglial Hmgb1 regulates postnatal astrocyte morphogenesis and cerebrovascular maturation

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Aug. 16, 2023

Abstract Astrocytes are intimately linked with brain blood vessels, an essential relationship for neuronal function. However, astroglial factors driving these physical and functional associations during postnatal development have yet to be identified. By characterizing structural transcriptional changes in mouse cortical astrocytes the first two weeks, we find that high-mobility group box 1 ( Hmgb1 ), normally upregulated injury involved adult cerebrovascular repair, is highly expressed at birth then decreases rapidly. Astrocyte-selective ablation of affects astrocyte morphology endfoot placement, alters distribution proteins connexin43 aquaporin-4, induces related cytoskeleton remodeling, profoundly disrupts endothelial ultrastructure. While lack does not affect blood-brain barrier or angiogenesis postnatally, it impairs neurovascular coupling behavior mice. These findings identify as important player gliovascular maturation.

Language: Английский

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Astrocytes regulate vascular endothelial responses to simulated deep space radiation in a human organ-on-a-chip model

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Aug. 30, 2022

Central nervous system (CNS) damage by galactic cosmic ray radiation is a major health risk for human deep space exploration. Simulated rays or their components, especially high Z-high energy particles such as 56Fe ions, cause neurodegeneration and neuroinflammation in rodent models. CNS can be partially mediated the blood-brain barrier, which regulates systemic interactions between rest of body. Astrocytes are cellular regulators barrier permeability that also modulate neuronal health. However, astrocyte roles regulating responses to remain little understood, tissue analogs. In this work, we used novel high-throughput organ-on-a-chip evaluate impairments functions 1-7 days after exposure 600 MeV/n simplified simulated rays. We show causes vascular permeability, oxidative stress, inflammation delayed activation pattern resembling brain injury. Furthermore, our results indicate astrocytes have dual role responses: they exacerbate acutely irradiation, followed switching more protective phenotype reducing stress pro-inflammatory cytokine chemokine secretion during subacute stage.

Language: Английский

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Effect of hyperbaric oxygen therapy for non-motor symptoms among patients with Parkinson's disease: A systematic review and meta-analysis

Clinical Rehabilitation, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 7, 2025

Objective To systematically evaluate the efficacy of hyperbaric oxygen therapy for non-motor symptoms in patients with Parkinson's disease. Data sources A systematic search was performed across several databases, including Chinese Science and Technology Periodical Database, Web Science, SinoMed, PubMed, Cochrane Library, Embase Wanfang databases up to 1 December 2024. Studies considered inclusion comprised randomised controlled trials pre–post control studies. Review methods The authors conducted data extraction literature screening procedures independently. selected studies’ quality evaluated using risk bias technique. Manager 5.3 used conduct meta-analyses, while Stata 15.0 utilised sensitivity analysis assess publication bias. Results Sixteen studies a total 1324 individuals satisfied criteria. results meta-analysis showed that significantly improved scores on Hamilton Anxiety Scale Depression compared baseline (both p < 0.05). Additionally, improvements were observed Montreal Cognitive Assessment, Mini-Mental State Examination, Disease Sleep Scale, Pittsburgh Quality Index, Kubota's Drinking Water Test Unified Rating III. Improvements sleep efficiency extension time also noted controls (all Conclusion findings indicate effectively alleviates such as anxiety, depression, cognitive impairments, disturbances, swallowing dysfunction, well improving motor function disease patients. Since protocol had significant differences between studies, further prospective rigorous methodology are needed.

Language: Английский

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