Modeling blood–brain barrier pathology in cerebrovascular disease in vitro: current and future paradigms

Andjelkovic, Anuska V.; Stamatovic, Svetlana M.; Phillips, Chelsea; Martínez-Revollar, Gabriela; Keep, Richard F.

doi:10.1186/s12987-020-00202-7

Cited by 44 publications

(34 citation statements)

References 208 publications

(331 reference statements)

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“…Moreover, JAMs, including JAMA, JAMB, JAMC, and JAML (junctional adhesion molecule), belong to this group. Additionally, Cx43, Claudin, Occludin, Esam, and VE-CADHERIN are localized in the same area [32,33]. (ii) The second group is important in regulating the movement of the cells through the space between the endothelial cells.…”

Section: Resultsmentioning

confidence: 99%

Paracellular and Transcellular Leukocytes Diapedesis Are Divergent but Interconnected Evolutionary Events

Mickael

Kubick

Klimovich³

et al. 2021

Genes

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Infiltration of the endothelial layer of the blood-brain barrier by leukocytes plays a critical role in health and disease. When passing through the endothelial layer during the diapedesis process lymphocytes can either follow a paracellular route or a transcellular one. There is a debate whether these two processes constitute one mechanism, or they form two evolutionary distinct migration pathways. We used artificial intelligence, phylogenetic analysis, HH search, ancestor sequence reconstruction to investigate further this intriguing question. We found that the two systems share several ancient components, such as RhoA protein that plays a critical role in controlling actin movement in both mechanisms. However, some of the key components differ between these two transmigration processes. CAV1 genes emerged during Trichoplax adhaerens, and it was only reported in transcellular process. Paracellular process is dependent on PECAM1. PECAM1 emerged from FASL5 during Zebrafish divergence. Lastly, both systems employ late divergent genes such as ICAM1 and VECAM1. Taken together, our results suggest that these two systems constitute two different mechanical sensing mechanisms of immune cell infiltrations of the brain, yet these two systems are connected. We postulate that the mechanical properties of the cellular polarity is the main driving force determining the migration pathway. Our analysis indicates that both systems coevolved with immune cells, evolving to a higher level of complexity in association with the evolution of the immune system.

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Section: Resultsmentioning

confidence: 99%

Paracellular and Transcellular Leukocytes Diapedesis Are Divergent but Interconnected Evolutionary Events

Mickael

Kubick

Klimovich³

et al. 2021

Genes

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“…Moving to engineering vascularized complex tissues, the blood-brain barrier (BBB) model has been generated by a hierarchical combination of ECs, neurons, and astrocytes based on a microfluidic platform (Andjelkovic et al, 2020). The sources of ECs for this purpose can be HUVECs, and primary brainderived microvascular ECs.…”

Section: Establishing Different Types Of Microvessels On a Chipmentioning

confidence: 99%

Rebuilding the Vascular Network: In vivo and in vitro Approaches

Meng

Xing

et al. 2021

Front. Cell Dev. Biol.

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As the material transportation system of the human body, the vascular network carries the transportation of materials and nutrients. Currently, the construction of functional microvascular networks is an urgent requirement for the development of regenerative medicine and in vitro drug screening systems. How to construct organs with functional blood vessels is the focus and challenge of tissue engineering research. Here in this review article, we first introduced the basic characteristics of blood vessels in the body and the mechanism of angiogenesis in vivo, summarized the current methods of constructing tissue blood vessels in vitro and in vivo, and focused on comparing the functions, applications and advantages of constructing different types of vascular chips to generate blood vessels. Finally, the challenges and opportunities faced by the development of this field were discussed.

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“…Metabolic plasticity of NVU/BBB cells driven by mitochondrial activity can be evaluated in vivo and in vitro; however, in vitro models provide more opportunities for dissecting signaling pathways and intercellular communication, mitochondria transfer or metabolites action in relation to NVU functional competence and BBB integrity. Up-to-date models are designed to reproduce the geometry of the NVU or BBB with endothelial cells and perivascular cells, and to examine the main aspects of the barrier activity [ 128 , 129 , 130 ].…”

Section: Application Of In Vitro Nvu/bbb Models For Studying Mitochondria-related Changes In Cell Metabolism: Current Trends and Challengmentioning

confidence: 99%

Blood–Brain Barrier and Neurovascular Unit In Vitro Models for Studying Mitochondria-Driven Molecular Mechanisms of Neurodegeneration

Салмина

Kharitonova

Gorina

et al. 2021

IJMS

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Pathophysiology of chronic neurodegeneration is mainly based on complex mechanisms related to aberrant signal transduction, excitation/inhibition imbalance, excitotoxicity, synaptic dysfunction, oxidative stress, proteotoxicity and protein misfolding, local insulin resistance and metabolic dysfunction, excessive cell death, development of glia-supported neuroinflammation, and failure of neurogenesis. These mechanisms tightly associate with dramatic alterations in the structure and activity of the neurovascular unit (NVU) and the blood–brain barrier (BBB). NVU is an ensemble of brain cells (brain microvessel endothelial cells (BMECs), astrocytes, pericytes, neurons, and microglia) serving for the adjustment of cell-to-cell interactions, metabolic coupling, local microcirculation, and neuronal excitability to the actual needs of the brain. The part of the NVU known as a BBB controls selective access of endogenous and exogenous molecules to the brain tissue and efflux of metabolites to the blood, thereby providing maintenance of brain chemical homeostasis critical for efficient signal transduction and brain plasticity. In Alzheimer’s disease, mitochondria are the target organelles for amyloid-induced neurodegeneration and alterations in NVU metabolic coupling or BBB breakdown. In this review we discuss understandings on mitochondria-driven NVU and BBB dysfunction, and how it might be studied in current and prospective NVU/BBB in vitro models for finding new approaches for the efficient pharmacotherapy of Alzheimer’s disease.

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Modeling blood–brain barrier pathology in cerebrovascular disease in vitro: current and future paradigms

Cited by 44 publications

References 208 publications

Paracellular and Transcellular Leukocytes Diapedesis Are Divergent but Interconnected Evolutionary Events

Paracellular and Transcellular Leukocytes Diapedesis Are Divergent but Interconnected Evolutionary Events

Rebuilding the Vascular Network: In vivo and in vitro Approaches

Blood–Brain Barrier and Neurovascular Unit In Vitro Models for Studying Mitochondria-Driven Molecular Mechanisms of Neurodegeneration

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