Microvascular blood-brain barrier alterations in isolated brain capillaries of mice over-expressing alpha-synuclein (Thy1-aSyn line 61)

Lau, Kristina; Porschen, Lisa T.; Richter, Franziska; Gericke, Birthe

doi:10.1016/j.nbd.2023.106298

Cited by 4 publications

(1 citation statement)

References 60 publications

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“…In another study, a PD mouse model that overexpresses human wild-type α-syn was analyzed, and several early BBB changes were detected. These included changes in striatal capillaries, decreased vascular density, alterations in AQP-4 coverage, reduced P-glycoprotein (P-gp) expression, increased LRP1 expression, deposition of pS129-α-syn, elevated expression of VCAM-1 and MMP-3, and an early reduction in the tight junction protein occludin [197]. These changes lead to a pronounced leakiness of the BBB when a toxic insult occurs, such as LPS injection.…”

Section: Bbb Alterations In Pd and The Immune Responsementioning

confidence: 99%

Experimental Models to Study Immune Dysfunction in the Pathogenesis of Parkinson’s Disease

Saponjic,

Mejías,

Nikolovski

et al. 2024

IJMS

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Parkinson’s disease (PD) is a chronic, age-related, progressive multisystem disease associated with neuroinflammation and immune dysfunction. This review discusses the methodological approaches used to study the changes in central and peripheral immunity in PD, the advantages and limitations of the techniques, and their applicability to humans. Although a single animal model cannot replicate all pathological features of the human disease, neuroinflammation is present in most animal models of PD and plays a critical role in understanding the involvement of the immune system (IS) in the pathogenesis of PD. The IS and its interactions with different cell types in the central nervous system (CNS) play an important role in the pathogenesis of PD. Even though culture models do not fully reflect the complexity of disease progression, they are limited in their ability to mimic long-term effects and need validation through in vivo studies. They are an indispensable tool for understanding the interplay between the IS and the pathogenesis of this disease. Understanding the immune-mediated mechanisms may lead to potential therapeutic targets for the treatment of PD. We believe that the development of methodological guidelines for experiments with animal models and PD patients is crucial to ensure the validity and consistency of the results.

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Section: Bbb Alterations In Pd and The Immune Responsementioning

confidence: 99%

Experimental Models to Study Immune Dysfunction in the Pathogenesis of Parkinson’s Disease

Saponjic,

Mejías,

Nikolovski

et al. 2024

IJMS

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Challenges and Future Perspectives in Modeling Neurodegenerative Diseases Using Organ‐on‐a‐Chip Technology

Pramotton,

Spitz,

Kamm

2024

Advanced Science

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Neurodegenerative diseases (NDDs) affect more than 50 million people worldwide, posing a significant global health challenge as well as a high socioeconomic burden. With aging constituting one of the main risk factors for some NDDs such as Alzheimer's disease (AD) and Parkinson's disease (PD), this societal toll is expected to rise considering the predicted increase in the aging population as well as the limited progress in the development of effective therapeutics. To address the high failure rates in clinical trials, legislative changes permitting the use of alternatives to traditional pre‐clinical in vivo models are implemented. In this regard, microphysiological systems (MPS) such as organ‐on‐a‐chip (OoC) platforms constitute a promising tool, due to their ability to mimic complex and human‐specific tissue niches in vitro. This review summarizes the current progress in modeling NDDs using OoC technology and discusses five critical aspects still insufficiently addressed in OoC models to date. Taking these aspects into consideration in the future MPS will advance the modeling of NDDs in vitro and increase their translational value in the clinical setting.

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Optimized Enrichment of Murine Blood-Brain Barrier Vessels with a Critical Focus on Network Hierarchy in Post-Collection Analysis

Abdelazim,

Barnes,

Stupin

et al. 2024

Preprint

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Cerebrovascular networks contain a unique region of interconnected capillaries known as the blood-brain barrier (BBB). Positioned between upstream arteries and downstream veins, these microvessels have unique structural features, such as the absence of vascular smooth muscle cells (vSMCs) and a relatively thin basement membrane, to facilitate highly efficient yet selective exchange between the circulation and the brain interstitium. This vital role in neurological health and function has garnered significant attention from the scientific community and inspired methodology for enriching BBB capillaries. Extensive characterization of the isolates from such protocols is essential for framing the results of follow-on experiments and analyses, providing the most accurate interpretation and assignment of BBB properties. Seeking to aid in these efforts, here we visually screened output samples using fluorescent labels and found considerable reduction of non-vascular cells following density gradient centrifugation (DGC) and subsequent filtration. Comparatively, this protocol enriched brain capillaries, though larger diameter vessels associated with vSMCs could not be fully excluded. Protein analysis further underscored the enrichment of vascular markers following DGC, with filtration preserving BBB-associated markers and reducing, though not fully removing, arterial/venous contributions. Transcriptional profiling followed similar trends of DGC plus filtration generating isolates with less non-vascular and non-capillary material included. Considering vascular network hierarchy inspired a more comprehensive assessment of the material yielded from brain microvasculature isolation protocols. This approach is important for providing an accurate representation of the cerebrovascular segments being used for data collection and assigning BBB properties specifically to capillaries relative to other regions of the brain vasculature.

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Microvascular blood-brain barrier alterations in isolated brain capillaries of mice over-expressing alpha-synuclein (Thy1-aSyn line 61)

Cited by 4 publications

References 60 publications

Experimental Models to Study Immune Dysfunction in the Pathogenesis of Parkinson’s Disease

Experimental Models to Study Immune Dysfunction in the Pathogenesis of Parkinson’s Disease

Challenges and Future Perspectives in Modeling Neurodegenerative Diseases Using Organ‐on‐a‐Chip Technology

Optimized Enrichment of Murine Blood-Brain Barrier Vessels with a Critical Focus on Network Hierarchy in Post-Collection Analysis

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