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Blood-Brain Barrier in CNS Injury and Repair 2023
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Blood-Brain Barrier in CNS Injury and Repair 2023

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (30 January 2024) | Viewed by 3712

Special Issue Editors

Dr. Aruna Sharma

E-Mail Website
Guest Editor
Department of Surgical Sciences, Akademiska Sjukhuset, Uppsala University, 751 85 Uppsala, Sweden
Interests: military medicine; high altitude brain pathology; blood–brain barrier; nanodrug delivery; stem cells; neuroregeneration; nanowired drug delivery; neurodegeneration; behavioural physiology; neurochemistry; Alzheimer’s disease; Parkinson’s disease; brain pathology; neurorepair
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Hari Shanker Sharma

E-Mail Website
Guest Editor
Department of Surgical Sciences, Akademiska Sjukhuset, Uppsala University, 751 85 Uppsala, Sweden
Interests: blood–brain barrier; brain edema; neurochemistry; neurophysiology; neuropathology; nanoneuroscience; nanoneuropharmacology; neuroregeneration; central nervous system injury; traumatic brain injury; neurorepair; military medicine; Alzheimer’s disease; Parkinson’s disease; neurotrophic factors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The blood–brain barrier (BBB) regulates the fluid environment of the brain strictly within a narrow limit. The BBB is anatomically positioned within the endothelial cells of the cerebral capillaries that are connected with tight junctions. Thus, the passage of substances, drugs, proteins, and other large molecules is severely restricted at the BBB. However, all kinds of brain diseases following trauma, ischemia, strenuous activity stress, psychiatric illnesses and/or psychostimulant overuse, etc. are associated with the breakdown of the BBB to large molecules, e.g., proteins. Additionally, several neurological diseases, e.g., Alzheimer’s, Parkinson’s, and Huntington’s disease, as well as amyotrophic lateral sclerosis, neuropathic pain, liver cirrhosis, hypertension and/or diabetes, and related chronic disorders are associated with the breakdown of the BBB. Furthermore, BBB breakdown allows the passage of serum proteins and other toxins into the fluid microenvironment of the central nervous system (CNS), resulting in cerebral edema formation and subsequent cellular injuries. Interestingly, no suitable therapeutic strategies have yet been worked out to treat such neurological diseases. This Special Issue will present new developments in the field of BBB research to improve current therapeutic measures as well as provide a platform to discuss the use of nanomedicine in several CNS diseases for the benefit of mankind. We ask experts in the field to contribute their latest research, perspectives, or reviews on this fascinating and rapidly progressing topic.

Dr. Aruna Sharma
Prof. Dr. Hari Shanker Sharma
Guest Editors

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
  • brain edema
  • neurodegeneration
  • neurorepair
  • cerebral blood flow
  • blood–spinal cord barrier
  • blood–CSF-barrier
  • Alzheimer’s disease
  • Parkinson’s disease
  • psychostimulants
  • brain pathology
  • nanomedicine

Published Papers (2 papers)

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Research

14 pages, 3069 KiB  
Article
Localized Increased Permeability of Blood–Brain Barrier for Antibody Conjugates in the Cuprizone Model of Demyelination
by Tatiana Abakumova, Anastasia Kuzkina, Philipp Koshkin, Daria Pozdeeva, Maxim Abakumov, Pavel Melnikov, Klavdia Ionova, Ilia Gubskii, Olga Gurina, Natalia Nukolova and Vladimir Chekhonin
Int. J. Mol. Sci. 2023, 24(16), 12688; https://doi.org/10.3390/ijms241612688 - 11 Aug 2023
Viewed by 1109
Abstract
The development of new neurotherapeutics depends on appropriate animal models being chosen in preclinical studies. The cuprizone model is an effective tool for studying demyelination and remyelination processes in the brain, but blood–brain barrier (BBB) integrity in the cuprizone model is still a [...] Read more.
The development of new neurotherapeutics depends on appropriate animal models being chosen in preclinical studies. The cuprizone model is an effective tool for studying demyelination and remyelination processes in the brain, but blood–brain barrier (BBB) integrity in the cuprizone model is still a topic for debate. Several publications claim that the BBB remains intact during cuprizone-induced demyelination; others demonstrate results that could explain the increased BBB permeability. In this study, we aim to analyze the permeability of the BBB for different macromolecules, particularly antibody conjugates, in a cuprizone-induced model of demyelination. We compared the traditional approach using Evans blue injection with subsequent dye extraction and detection of antibody conjugates using magnetic resonance imaging (MRI) and confocal microscopy to analyze BBB permeability in the cuprizone model. First, we validated our model of demyelination by performing T2-weighted MRI, diffusion tensor imaging, quantitative rt-PCR to detect changes in mRNA expression of myelin basic protein and proteolipid protein, and Luxol fast blue histological staining of myelin. Intraperitoneal injection of Evans blue did not result in any differences between the fluorescent signal in the brain of healthy and cuprizone-treated mice (IVIS analysis with subsequent dye extraction). In contrast, intravenous injection of antibody conjugates (anti-GFAP or non-specific IgG) after 4 weeks of a cuprizone diet demonstrated accumulation in the corpus callosum of cuprizone-treated mice both by contrast-enhanced MRI (for gadolinium-labeled antibodies) and by fluorescence microscopy (for Alexa488-labeled antibodies). Our results suggest that the methods with better sensitivity could detect the accumulation of macromolecules (such as fluorescent-labeled or gadolinium-labeled antibody conjugates) in the brain, suggesting a local BBB disruption in the demyelinating area. These findings support previous investigations that questioned BBB integrity in the cuprizone model and demonstrate the possibility of delivering antibody conjugates to the corpus callosum of cuprizone-treated mice. Full article
(This article belongs to the Special Issue Blood-Brain Barrier in CNS Injury and Repair 2023)
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24 pages, 8298 KiB  
Article
Modelling a Human Blood-Brain Barrier Co-Culture Using an Ultrathin Silicon Nitride Membrane-Based Microfluidic Device
by Diana Hudecz, Molly C. McCloskey, Sandra Vergo, Søren Christensen, James L. McGrath and Morten S. Nielsen
Int. J. Mol. Sci. 2023, 24(6), 5624; https://doi.org/10.3390/ijms24065624 - 15 Mar 2023
Cited by 3 | Viewed by 2265
Abstract
Understanding the vesicular trafficking of receptors and receptor ligands in the brain capillary endothelium is essential for the development of the next generations of biologics targeting neurodegenerative diseases. Such complex biological questions are often approached by in vitro models in combination with various [...] Read more.
Understanding the vesicular trafficking of receptors and receptor ligands in the brain capillary endothelium is essential for the development of the next generations of biologics targeting neurodegenerative diseases. Such complex biological questions are often approached by in vitro models in combination with various techniques. Here, we present the development of a stem cell-based human in vitro blood-brain barrier model composed of induced brain microvascular endothelial cells (iBMECs) on the modular µSiM (a microdevice featuring a silicon nitride membrane) platform. The µSiM was equipped with a 100 nm thick nanoporous silicon nitride membrane with glass-like imaging quality that allowed the use of high-resolution in situ imaging to study the intracellular trafficking. As a proof-of-concept experiment, we investigated the trafficking of two monoclonal antibodies (mAb): an anti-human transferrin receptor mAb (15G11) and an anti-basigin mAb (#52) using the µSiM-iBMEC-human astrocyte model. Our results demonstrated effective endothelial uptake of the selected antibodies; however, no significant transcytosis was observed when the barrier was tight. In contrast, when the iBMECs did not form a confluent barrier on the µSiM, the antibodies accumulated inside both the iBMECs and astrocytes, demonstrating that the cells have an active endocytic and subcellular sorting machinery and that the µSiM itself does not hinder antibody transport. In conclusion, our µSiM-iBMEC-human astrocyte model provides a tight barrier with endothelial-like cells, which can be used for high-resolution in situ imaging and for studying receptor-mediated transport and transcytosis in a physiological barrier. Full article
(This article belongs to the Special Issue Blood-Brain Barrier in CNS Injury and Repair 2023)
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