The Blood–Brain Barrier, an Evolving Concept Based on Technological Advances and Cell–Cell Communications

Menaceur, Camille; Gosselet, Fabien; Fénart, Laurence; Saint-Pol, Julien

doi:10.3390/cells11010133

Cited by 24 publications

(17 citation statements)

References 161 publications

(209 reference statements)

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“…The NHP models used differ by the presence of astrocytes and pericytes which can have a major impact on permeability and protein expression. Pericyte coverage is essential to the barrier integrity [ 125 ], moreover pericyte signaling to endothelial cells via integrins has recently been reported to impact BBB permeability [ 112 ]. The PharmaCo-Cell® model is certainly the most relevant to this study, as immunization was performed with NHP cells, and this model incorporates cells from the neurovascular unit.…”

Section: Discussionmentioning

confidence: 99%

An innovative strategy to identify new targets for delivering antibodies to the brain has led to the exploration of the integrin family

et al. 2022

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Background Increasing brain exposure of biotherapeutics is key to success in central nervous system disease drug discovery. Accessing the brain parenchyma is especially difficult for large polar molecules such as biotherapeutics and antibodies because of the blood-brain barrier. We investigated a new immunization strategy to identify novel receptors mediating transcytosis across the blood-brain barrier. Method We immunized mice with primary non-human primate brain microvascular endothelial cells to obtain antibodies. These antibodies were screened for their capacity to bind and to be internalized by primary non-human primate brain microvascular endothelial cells and Human Cerebral Microvascular Endothelial Cell clone D3. They were further evaluated for their transcytosis capabilities in three in vitro blood-brain barrier models. In parallel, their targets were identified by two different methods and their pattern of binding to human tissue was investigated using immunohistochemistry. Results 12 antibodies with unique sequence and internalization capacities were selected amongst more than six hundred. Aside from one antibody targeting Activated Leukocyte Cell Adhesion Molecule and one targeting Striatin3, most of the other antibodies recognized β1 integrin and its heterodimers. The antibody with the best transcytosis capabilities in all blood-brain barrier in vitro models and with the best binding capacity was an anti-αnβ1 integrin. In comparison, commercial anti-integrin antibodies performed poorly in transcytosis assays, emphasizing the originality of the antibodies derived here. Immunohistochemistry studies showed specific vascular staining on human and non-human primate tissues. Conclusions This transcytotic behavior has not previously been reported for anti-integrin antibodies. Further studies should be undertaken to validate this new mechanism in vivo and to evaluate its potential in brain delivery.

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Section: Discussionmentioning

confidence: 99%

An innovative strategy to identify new targets for delivering antibodies to the brain has led to the exploration of the integrin family

et al. 2022

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“…They originate from NPCs and radial glial cells (RGCs) in the subventricular zone, express glial fibrillary acidic protein (GFAP), a specific marker for astrocytes in some regions of the brain, and migrate to the cortical layers, to fill the neuronal space, supporting and dividing neurons. Astrocytes are involved in the regulation of neurotransmitter release and recycling, K + and Ca 2+ balance, synaptogenesis, plasticity maintenance, and BBB homeostasis [ 30 ]. When stimulated by the K + and neurotransmitters released by neurons, astrocytes depolarize and trigger the elevation of [Ca 2+ ] i and [K + ] i and release of vesicle ATP, regulating the excitability of the axon initial segment of excitatory neurons and the conduction velocity of myelinated axons, thereby controlling neuronal energy metabolism and synaptic numbers [ 31 , 32 ] ( Figure 5 ).…”

Section: Roles Of Glial Cells In Physiological and Pathological Statesmentioning

confidence: 99%

Research Progress on the Role of RNA m6A Modification in Glial Cells in the Regulation of Neurological Diseases

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et al. 2022

Biomolecules

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Glial cells are the most abundant and widely distributed cells that maintain cerebral homeostasis in the central nervous system. They mainly include microglia, astrocytes, and the oligodendrocyte lineage cells. Moreover, glial cells may induce pathological changes, such as inflammatory responses, demyelination, and disruption of the blood–brain barrier, to regulate the occurrence and development of neurological diseases through various molecular mechanisms. Furthermore, RNA m6A modifications are involved in various pathological processes associated with glial cells. In this review, the roles of glial cells in physiological and pathological states, as well as advances in understanding the mechanisms by which glial cells regulate neurological diseases under RNA m6A modification, are summarized, hoping to provide new perspectives on the deeper mechanisms and potential therapeutic targets for neurological diseases.

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“…The blood–brain barrier (BBB), a unique structure in the human body, is one of the three main barriers along with the blood–leptomeningeal barrier, and the blood–cerebrospinal fluid barrier that separates the brain from peripheral tissues [ 1 ]. Its complex cytoarchitecture provides a highly selective environment that allows a bidirectional but strictly controlled passage of different solutes between the brain and the systemic circulation [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

In Vitro Modeling of the Blood–Brain Barrier for the Study of Physiological Conditions and Alzheimer’s Disease

et al. 2022

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The blood–brain barrier (BBB) is an essential structure for the maintenance of brain homeostasis. Alterations to the BBB are linked with a myriad of pathological conditions and play a significant role in the onset and evolution of neurodegenerative diseases, including Alzheimer’s disease. Thus, a deeper understanding of the BBB’s structure and function is mandatory for a better knowledge of neurodegenerative disorders and the development of effective therapies. Because studying the BBB in vivo imposes overwhelming difficulties, the in vitro approach remains the main possible way of research. With many in vitro BBB models having been developed over the last years, the main aim of this review is to systematically present the most relevant designs used in neurological research. In the first part of the article, the physiological and structural–functional parameters of the human BBB are detailed. Subsequently, available BBB models are presented in a comparative approach, highlighting their advantages and limitations. Finally, the new perspectives related to the study of Alzheimer’s disease with the help of novel devices that mimic the in vivo human BBB milieu gives the paper significant originality.

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The Blood–Brain Barrier, an Evolving Concept Based on Technological Advances and Cell–Cell Communications

Cited by 24 publications

References 161 publications

An innovative strategy to identify new targets for delivering antibodies to the brain has led to the exploration of the integrin family

An innovative strategy to identify new targets for delivering antibodies to the brain has led to the exploration of the integrin family

Research Progress on the Role of RNA m6A Modification in Glial Cells in the Regulation of Neurological Diseases

In Vitro Modeling of the Blood–Brain Barrier for the Study of Physiological Conditions and Alzheimer’s Disease

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