The vascular basement membrane in the healthy and pathological brain

Thomsen, Maj Schneider; Routhe, Lisa Juul; Moos, Torben

doi:10.1177/0271678x17722436

Cited by 345 publications

(298 citation statements)

References 195 publications

(281 reference statements)

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“…An essential, functional participant of the neurovascular unit is the basement membrane. Basement membrane in the brain is primarily composed of laminins and collagen IV . We found, however, that hCMEC/D3 cellular morphology and adherence to the internal glass and PDMS surfaces were optimal when coated with human fibronectin.…”

Section: Resultsmentioning

confidence: 58%

A microfluidic model of human brain (μHuB) for assessment of blood brain barrier

Brown

Nowak

Bayles

et al. 2019

Bioengineering & Transla Med

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Microfluidic cellular models, commonly referred to as “organs‐on‐chips,” continue to advance the field of bioengineering via the development of accurate and higher throughput models, captivating the essence of living human organs. This class of models can mimic key in vivo features, including shear stresses and cellular architectures, in ways that cannot be realized by traditional two‐dimensional in vitro models. Despite such progress, current organ‐on‐a‐chip models are often overly complex, require highly specialized setups and equipment, and lack the ability to easily ascertain temporal and spatial differences in the transport kinetics of compounds translocating across cellular barriers. To address this challenge, we report the development of a three‐dimensional human blood brain barrier (BBB) microfluidic model (μHuB) using human cerebral microvascular endothelial cells (hCMEC/D3) and primary human astrocytes within a commercially available microfluidic platform. Within μHuB, hCMEC/D3 monolayers withstood physiologically relevant shear stresses (2.73 dyn/cm 2 ) over a period of 24 hr and formed a complete inner lumen, resembling in vivo blood capillaries. Monolayers within μHuB expressed phenotypical tight junction markers (Claudin‐5 and ZO‐1), which increased expression after the presence of hemodynamic‐like shear stress. Negligible cell injury was observed when the monolayers were cultured statically, conditioned to shear stress, and subjected to nonfluorescent dextran (70 kDa) transport studies. μHuB experienced size‐selective permeability of 10 and 70 kDa dextrans similar to other BBB models. However, with the ability to probe temporal and spatial evolution of solute distribution, μHuBs possess the ability to capture the true variability in permeability across a cellular monolayer over time and allow for evaluation of the full breadth of permeabilities that would otherwise be lost using traditional end‐point sampling techniques. Overall, the μHuB platform provides a simplified, easy‐to‐use model to further investigate the complexities of the human BBB in real‐time and can be readily adapted to incorporate additional cell types of the neurovascular unit and beyond.

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Section: Resultsmentioning

confidence: 58%

A microfluidic model of human brain (μHuB) for assessment of blood brain barrier

Brown

Nowak

Bayles

et al. 2019

Bioengineering & Transla Med

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“…The brain has high‐metabolic demands and its blood supply has fundamental roles to play (Thomsen et al . ). Blood vessel basement membrane is crucial to vessel stability and functional integrity.…”

Section: Kspgs Of the Cns/pnsmentioning

confidence: 97%

Keratan sulfate (KS)‐proteoglycans and neuronal regulation in health and disease: the importance ofKS‐glycodynamics and interactive capability with neuroregulatory ligands

Melrose

2019

Journal of Neurochemistry

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Compared to the other classes of glycosaminoglycans (GAGs), that is, chondroitin/dermatan sulfate, heparin/heparan sulfate and hyaluronan, keratan sulfate (KS), have the least known of its interactive properties. In the human body, the cornea and the brain are the two most abundant tissue sources of KS. Embryonic KS is synthesized as a linear poly‐N‐acetyllactosamine chain of d‐galactose‐GlcNAc repeat disaccharides which become progressively sulfated with development, sulfation of GlcNAc is more predominant than galactose. KS contains multi‐sulfated high‐charge density, monosulfated and non‐sulfated poly‐N‐acetyllactosamine regions and thus is a heterogeneous molecule in terms of chain length and charge distribution. A recent proteomics study on corneal KS demonstrated its interactivity with members of the Slit‐Robbo and Ephrin‐Ephrin receptor families and proteins which regulate Rho GTPase signaling and actin polymerization/depolymerization in neural development and differentiation. KS decorates a number of peripheral nervous system/CNS proteoglycan (PG) core proteins. The astrocyte KS‐PG abakan defines functional margins of the brain and is up‐regulated following trauma. The chondroitin sulfate/KS PG aggrecan forms perineuronal nets which are dynamic neuroprotective structures with anti‐oxidant properties and roles in neural differentiation, development and synaptic plasticity. Brain phosphacan a chondroitin sulfate, KS, HNK‐1 PG have roles in neural development and repair. The intracellular microtubule and synaptic vesicle KS‐PGs MAP1B and SV2 have roles in metabolite transport, storage, and export of neurotransmitters and cytoskeletal assembly. MAP1B has binding sites for tubulin and actin through which it promotes cytoskeletal development in growth cones and is highly expressed during neurite extension. The interactive capability of KS with neuroregulatory ligands indicate varied roles for KS‐PGs in development and regenerative neural processes.

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“…Extracellular matrix (ECM) coverage is fundamental for appropriate organization and functioning of various tissues (Naba et al ., ). One unique form of the ECM is the basement membrane (BM), an amorphous layer located at the interface of the circulation system and the central nervous system (CNS) (Hallmann et al ., ; Domogatskaya, Rodin & Tryggvason, ; Thomsen, Routhe & Moos, ). Although the composition of the BM varies depending on tissue type and developmental stage (Miner et al ., ), four major components (laminin, type IV collagen, nidogen, and heparin sulfate proteoglycans) are found ubiquitously in all types of BM at any stage (Frantz, Stewart & Weaver, ).…”

Section: Introductionmentioning

confidence: 99%

“…Extracellular matrix (ECM) coverage is fundamental for appropriate organization and functioning of various tissues (Naba et al, 2016). One unique form of the ECM is the basement membrane (BM), an amorphous layer located at the interface of the circulation system and the central nervous system (CNS) (Hallmann et al, 2005;Domogatskaya, Rodin & Tryggvason, 2012;Thomsen, Routhe & Moos, 2017).…”

Section: Introductionmentioning

confidence: 99%

Laminins and their receptors in the CNS

Nirwane

Yao

2018

Biological Reviews

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Laminin, an extracellular matrix protein, is widely expressed in the central nervous system (CNS). By interacting with integrin and non-integrin receptors, laminin exerts a large variety of important functions in the CNS in both physiological and pathological conditions. Due to the existence of many laminin isoforms and their differential expression in various cell types in the CNS, the exact functions of each individual laminin molecule in CNS development and homeostasis remain largely unclear. In this review, we first briefly introduce the structure and biochemistry of laminins and their receptors. Next, the dynamic expression of laminins and their receptors in the CNS during both development and in adulthood is summarized in a cell-type-specific manner, which allows appreciation of their functional redundancy/compensation. Furthermore, we discuss the biological functions of laminins and their receptors in CNS development, blood-brain barrier (BBB) maintenance, neurodegeneration, stroke, and neuroinflammation. Last, key challenges and potential future research directions are summarized and discussed. Our goals are to provide a synthetic review to stimulate future studies and promote the formation of new ideas/hypotheses and new lines of research in this field.

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The vascular basement membrane in the healthy and pathological brain

Cited by 345 publications

References 195 publications

A microfluidic model of human brain (μHuB) for assessment of blood brain barrier

A microfluidic model of human brain (μHuB) for assessment of blood brain barrier

Keratan sulfate (KS)‐proteoglycans and neuronal regulation in health and disease: the importance ofKS‐glycodynamics and interactive capability with neuroregulatory ligands

Laminins and their receptors in the CNS

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