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Advanced Research Progress of Blood-Brain Barrier
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Advanced Research Progress of Blood-Brain Barrier

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (20 March 2025) | Viewed by 4552

Special Issue Editor

Dr. Cucullo Luca

E-Mail Website
Guest Editor
Department of Foundational Medical Studies, Oakland University William Beaumont School of Medicine, Rochester, MI 48309, USA
Interests: in vitro neurovascular modeling; environmental and cellular modulation of BBB functions; CNS drug delivery; toxicology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The blood–brain barrier (BBB) is a complex dynamic interface between the blood and the central nervous system (CNS), which plays the critical role of regulating the homeostatic, nutritive and immune environments of the CNS, as well as the exchange of informational molecules between the CNS and periphery. BBB impairments have been strongly associated with the onset and progression of many neurological disorders, while also representing a major hindrance to CNS drug delivery. There is a need to further our understanding of the molecular mechanisms regulating BBB functions, including its physiological and pathological responses to bloodborne substances and xenobiotics, which also comprise putative brain-targeting therapeutics.

This Special Issue of the International Journal of Molecular Sciences welcomes both original research articles and review papers that deal with the molecular mechanisms underpinning the BBB in health and disease, as well as recent advances in experimental in vitro technologies that can further our understanding of the BBB and aid the process of CNS drug discovery.

Dr. Cucullo Luca
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • blood–brain barrier
  • endothelium
  • glia
  • drug discovery
  • physiology, in vitro
  • mechanism
  • neurovascular
  • microcapillary
  • permeability

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Published Papers (3 papers)

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Research

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21 pages, 5414 KiB  
Article
Transcriptome and Functional Comparison of Primary and Immortalized Endothelial Cells of the Human Choroid Plexus at the Blood–Cerebrospinal Fluid Barrier
by Lea Denzer, Walter Muranyi, Rosanna Herold, Carolin Stump-Guthier, Hiroshi Ishikawa, Carsten Sticht, Horst Schroten, Christian Schwerk and Stefan Weichert
Int. J. Mol. Sci. 2025, 26(4), 1779; https://doi.org/10.3390/ijms26041779 - 19 Feb 2025
Viewed by 588
Abstract
The human choroid plexus (CP) is the location of the blood–cerebrospinal fluid (CSF) barrier (BCSFB). Whereas the epithelial cells of the CP mainly contribute to the formation of the BCSFB, the vessels of the CP are built by fenestrated endothelial cells. Still, the [...] Read more.
The human choroid plexus (CP) is the location of the blood–cerebrospinal fluid (CSF) barrier (BCSFB). Whereas the epithelial cells of the CP mainly contribute to the formation of the BCSFB, the vessels of the CP are built by fenestrated endothelial cells. Still, the CP endothelium can contribute to barrier function. By ectopic expression of human telomerase reverse transcriptase (hTERT) in primary human CP endothelial cells (HCPEnCs), we recently generated and characterized immortalized HCPEnCs (iHCPEnCs). Here, we compared primary cells of the sixth passage (HCPEnCs p6) with a lower (p20) and a higher passage (p50) of iHCPEnCs by transcriptome analysis. A high concordance of HCPEnCs and both passages of iHCPEnCs was observed, as only small proportions of the transcripts examined were significantly altered. Differentially expressed genes (DEGs) were identified and assigned to potentially affected biological processes by gene set enrichment analysis (GSEA). Various components of the endothelial barrier-relevant Wnt signaling were detected in HCPEnCs and iHCPEnCs. Functional analysis of HCPEnCs and iHCPEnCs showed equal marginal activation of Wnt signaling, supporting the downregulation of β-catenin (CTNNB) signaling in CP endothelial cells, and a contribution to the barrier function by the CP endothelium was retained until passage 100 (p100) of iHCPEnCs. Overall, our data support the suitability of iHCPEnCs as an in vitro model of the CP endothelium over extended passages. Full article
(This article belongs to the Special Issue Advanced Research Progress of Blood-Brain Barrier)
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16 pages, 4754 KiB  
Article
Evaluation of Blood–Brain Barrier Disruption Using Low- and High-Molecular-Weight Complexes in a Single Brain Sample in a Rat Traumatic Brain Injury Model: Comparison to an Established Magnetic Resonance Imaging Technique
by Vladislav Zvenigorodsky, Benjamin F. Gruenbaum, Ilan Shelef, Anat Horev, Abed N. Azab, Anna Oleshko, Mammduch Abu-Rabia, Shahar Negev, Alexander Zlotnik, Israel Melamed and Matthew Boyko
Int. J. Mol. Sci. 2024, 25(20), 11241; https://doi.org/10.3390/ijms252011241 - 19 Oct 2024
Cited by 1 | Viewed by 1601
Abstract
Traumatic brain injury (TBI), a major cause of death and disability among young people, leads to significant public health and economic challenges. Despite its frequency, treatment options remain largely unsuitable. However, examination of the blood–brain barrier (BBB) can assist with understanding the mechanisms [...] Read more.
Traumatic brain injury (TBI), a major cause of death and disability among young people, leads to significant public health and economic challenges. Despite its frequency, treatment options remain largely unsuitable. However, examination of the blood–brain barrier (BBB) can assist with understanding the mechanisms and dynamics of brain dysfunction, which affects TBI sufferers secondarily to the injury. Here, we present a rat model of TBI focused on two standard BBB assessment markers, high- and low-molecular-weight complexes, in order to understand BBB disruption. In addition, we tested a new technique to evaluate BBB disruption on a single brain set, comparing the new technique with neuroimaging. A total of 100 Sprague–Dawley rats were separated into the following five groups: naive rats (n = 20 rats), control rats with administration (n = 20 rats), and TBI rats (n = 60 rats). Rats were assessed at different time points after the injury to measure BBB disruption using low- and high-molecular-weight complexes. Neurological severity score was evaluated at baseline and at 24 h following TBI. During the neurological exam after TBI, the rats were scanned with magnetic resonance imaging and euthanized for assessment of the BBB permeability. We found that the two markers displayed different examples of BBB disruption in the same set of brain tissues over the period of a week. Our innovative protocol for assessing BBB permeability using high- and low-molecular-weight complexes markers in a single brain set showed appropriate results. Additionally, we determined the lower limit of sensitivity, therefore demonstrating the accuracy of this method. Full article
(This article belongs to the Special Issue Advanced Research Progress of Blood-Brain Barrier)
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Review

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23 pages, 2667 KiB  
Review
Advances and Challenges of Bioassembly Strategies in Neurovascular In Vitro Modeling: An Overview of Current Technologies with a Focus on Three-Dimensional Bioprinting
by Salvatore Mancuso, Aditya Bhalerao and Luca Cucullo
Int. J. Mol. Sci. 2024, 25(20), 11000; https://doi.org/10.3390/ijms252011000 - 12 Oct 2024
Cited by 2 | Viewed by 1778
Abstract
Bioassembly encompasses various techniques such as bioprinting, microfluidics, organoids, and self-assembly, enabling advances in tissue engineering and regenerative medicine. Advancements in bioassembly technologies have enabled the precise arrangement and integration of various cell types to more closely mimic the complexity functionality of the [...] Read more.
Bioassembly encompasses various techniques such as bioprinting, microfluidics, organoids, and self-assembly, enabling advances in tissue engineering and regenerative medicine. Advancements in bioassembly technologies have enabled the precise arrangement and integration of various cell types to more closely mimic the complexity functionality of the neurovascular unit (NVU) and that of other biodiverse multicellular tissue structures. In this context, bioprinting offers the ability to deposit cells in a spatially controlled manner, facilitating the construction of interconnected networks. Scaffold-based assembly strategies provide structural support and guidance cues for cell growth, enabling the formation of complex bio-constructs. Self-assembly approaches utilize the inherent properties of cells to drive the spontaneous organization and interaction of neuronal and vascular components. However, recreating the intricate microarchitecture and functional characteristics of a tissue/organ poses additional challenges. Advancements in bioassembly techniques and materials hold great promise for addressing these challenges. The further refinement of bioprinting technologies, such as improved resolution and the incorporation of multiple cell types, can enhance the accuracy and complexity of the biological constructs; however, developing bioinks that support the growth of cells, viability, and functionality while maintaining compatibility with the bioassembly process remains an unmet need in the field, and further advancements in the design of bioactive and biodegradable scaffolds will aid in controlling cell adhesion, differentiation, and vascularization within the engineered tissue. Additionally, integrating advanced imaging and analytical techniques can provide real-time monitoring and characterization of bioassembly, aiding in quality control and optimization. While challenges remain, ongoing research and technological advancements propel the field forward, paving the way for transformative developments in neurovascular research and tissue engineering. This work provides an overview of the advancements, challenges, and future perspectives in bioassembly for fabricating neurovascular constructs with an add-on focus on bioprinting technologies. Full article
(This article belongs to the Special Issue Advanced Research Progress of Blood-Brain Barrier)
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