Barrier Formation and Homeostasis in the Vertebrate Brain

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Cellular Biochemistry".

Deadline for manuscript submissions: 30 June 2025 | Viewed by 1866

Special Issue Editors


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Guest Editor
Department of Pediatrics, Division of Neonatology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
Interests: vasculogenesis and angiogenesis mechanisms in zebrafish and mouse brains; vessel and axon guidance; translational models of disease; cilia biology

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Guest Editor
Department of Pediatrics, Division of Neonatology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
Interests: brian endothelium; cilia biology; brain vascular stability; vascular diseases; developmental biology

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Guest Editor
Department of Pediatrics, Division of Neonatology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
Interests: translational models of cerebrovascular diseases; cilia biology; cerebrovascular inflammation and homeostasis; TBI; vascular dementia; neurovascular–immune system crosstalk

Special Issue Information

Dear Colleagues,

In this Special Edition, we invite you to submit articles that study the various barriers associated with child and adult brains. One of the key barriers, namely the blood–brain barrier, is associated with preserving tissue homeostasis in the brain, and the deregulation of this barrier is associated with genetic and non-genetic conditions. Other barriers, such as the blood–retinal barrier, blood–lymph barrier and the blood–cerebrospinal fluid barrier, are also equally important, and we welcome studies that investigate these barriers. Studies focused on cell–cell interactions and the mechanisms underlying barrier formation or disruption are welcome. Approaches utilizing 3D microfluidic-based primary cell culture model systems, organoids, induced pluripotent stem cells, zebrafish, rodent model systems and human brain tissue are welcome. Computational modelling studies that mimic and provide novel hypotheses in barrier formation will also be considered. In general, we are interested in a multi-faceted innovative approach to barrier formation in vertebrates, and its role in disease. Endothelial barrier formation in tissues outside the brain will also be considered on a case-by-case basis. Original articles, reviews, hypotheses, and perspectives are welcome. Studies must be focused on basic science using in vitro, in vivo, and pre-clinical models. Manuscripts with exclusive clinical studies will not be considered. 

Prof. Dr. Ramani Ramchandran
Dr. Karthikeyan Thirugnanam
Dr. Ankan Gupta
Guest Editors

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Keywords

  • brain endothelial cell
  • pericytes
  • choroid plexus
  • retina
  • lymphatic
  • blood
  • astrocytes
  • oligodendrocytes
  • brain ventricle
  • microglia

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Published Papers (2 papers)

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Research

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22 pages, 4005 KiB  
Article
Transcriptional Responses of In Vitro Blood–Brain Barrier Models to Shear Stress
by Koji L. Foreman, Benjamin D. Gastfriend, Moriah E. Katt, Sean P. Palecek and Eric V. Shusta
Biomolecules 2025, 15(2), 193; https://doi.org/10.3390/biom15020193 - 29 Jan 2025
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Abstract
Endothelial cells throughout the body sense blood flow, eliciting transcriptional and phenotypic responses. The brain endothelium, known as the blood–brain barrier (BBB), possesses unique barrier and transport properties, which are in part regulated by blood flow. We utilized RNA sequencing to analyze the [...] Read more.
Endothelial cells throughout the body sense blood flow, eliciting transcriptional and phenotypic responses. The brain endothelium, known as the blood–brain barrier (BBB), possesses unique barrier and transport properties, which are in part regulated by blood flow. We utilized RNA sequencing to analyze the transcriptome of primary cultured rat brain microvascular endothelial cells (BMECs), as well as three human induced pluripotent stem cell-derived models. We compared the transcriptional responses of these cells to either low (0.5 dyne/cm2) or high (12 dyne/cm2) shear stresses, and subsequent analyses identified genes and pathways that were influenced by shear including key BBB-associated genes (SLC2A1, LSR, PLVAP) and canonical endothelial shear-stress-response transcription factors (KLF2, KLF4). In addition, our analysis suggests that shear alone is insufficient to rescue the de-differentiation caused by in vitro primary BMEC culture. Overall, these datasets and analyses provide new insights into the influence of shear on BBB models that will aid in model selection and guide further model development. Full article
(This article belongs to the Special Issue Barrier Formation and Homeostasis in the Vertebrate Brain)
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Review

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20 pages, 2087 KiB  
Review
Caveolae-Mediated Transcytosis and Its Role in Neurological Disorders
by Kunjian Yang, Qian Li, Yushuang Ruan, Yuanpeng Xia and Zhi Fang
Biomolecules 2025, 15(4), 456; https://doi.org/10.3390/biom15040456 - 21 Mar 2025
Viewed by 454
Abstract
The blood–brain barrier (BBB) controls the flow of substances to maintain a homeostatic environment in the brain, which is highly regulated and crucial for the normal function of the central nervous system (CNS). Brain endothelial cells (bECs), which are directly exposed to blood, [...] Read more.
The blood–brain barrier (BBB) controls the flow of substances to maintain a homeostatic environment in the brain, which is highly regulated and crucial for the normal function of the central nervous system (CNS). Brain endothelial cells (bECs), which are directly exposed to blood, play the most important role in maintaining the integrity of the BBB. Unlike endothelial cells in other tissues, bECs have two unique features: specialized endothelial tight junctions and actively suppressed transcellular vesicle trafficking (transcytosis). These features help to maintain the relatively low permeability of the CNS barrier. In addition to the predominant role of tight junctions in the BBB, caveolae-mediated adsorptive transcytosis has attracted much interest in recent years. The active suppression of transcytosis is dynamically regulated during development and in response to diseases. Altered caveolae-mediated transcytosis of bECs has been reported in several neurological diseases, but the understanding of this process in bECs is limited. Here, we review the process of caveolae-mediated transcytosis based on previous studies and discuss its function in the breakdown of the BBB in neurological disorders. Full article
(This article belongs to the Special Issue Barrier Formation and Homeostasis in the Vertebrate Brain)
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