For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
0
views
68
references
 Top references
cited by
14
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      425
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Increased blood-brain barrier hyperpermeability coincides with mast cell activation early under cuprizone administration

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The cuprizone induced animal model of demyelination is characterized by demyelination in many regions of the brain with high levels of demyelination in the corpus callosum as well as changes in neuronal function by 4–6 weeks of exposure. The model is used as a tool to study demyelination and subsequent degeneration as well as therapeutic interventions on these effects. Historically, the cuprizone model has been shown to contain no alterations to blood-brain barrier integrity, a key feature in many diseases that affect the central nervous system. Cuprizone is generally administered for 4–6 weeks to obtain maximal demyelination and degeneration. However, emerging evidence has shown that the effects of cuprizone on the brain may occur earlier than measurable gross demyelination. This study sought to investigate changes to blood-brain barrier permeability early in cuprizone administration. Results showed an increase in blood-brain barrier permeability and changes in tight junction protein expression as early as 3 days after beginning cuprizone treatment. These changes preceded glial morphological activation and demyelination known to occur during cuprizone administration. Increases in mast cell presence and activity were measured alongside the increased permeability implicating mast cells as a potential source for the blood-brain barrier disruption. These results provide further evidence of blood-brain barrier alterations in the cuprizone model and a target of therapeutic intervention in the prevention of cuprizone-induced pathology. Understanding how mast cells become activated under cuprizone and if they contribute to blood-brain barrier alterations may give further insight into how and when the blood-brain barrier is affected in CNS diseases. In summary, cuprizone administration causes an increase in blood-brain barrier permeability and this permeability coincides with mast cell activation.

          Related collections

          Most cited references68

          • Record: found
          • Abstract: found
          • Article: not found

          Integrated signalling pathways for mast-cell activation.

          Alasdair M Gilfillan, Christine Tkaczyk (2006)
          Mast-cell activation mediated by the high-affinity receptor for IgE (FcepsilonRI) is considered to be a key event in the allergic inflammatory response. However, in a physiological setting, other receptors, such as KIT, might also markedly influence the release of mediators by mast cells. Recent studies have provided evidence that FcepsilonRI-dependent degranulation is regulated by two complementary signalling pathways, one of which activates phospholipase Cgamma and the other of which activates phosphatidylinositol 3-kinase, using specific transmembrane and cytosolic adaptor molecules. In this Review, we discuss the evidence for these interacting pathways and describe how the capacity of KIT, and other receptors, to influence FcepsilonRI-dependent mast-cell-mediator release might be a function of the relative abilities of these receptors to activate these alternative pathways.
          Article 0 comments Cited 211 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Astrocytes induce blood-brain barrier properties in endothelial cells.

            R Janzer, M Raff (1987)
            The highly impermeable tight junctions between endothelial cells forming the capillaries and venules in the central nervous system (CNS) of higher vertebrates are thought to be responsible for the blood-brain barrier that impedes the passive diffusion of solutes from the blood into the extracellular space of the CNS. The ability of CNS endothelial cells to form a blood-brain barrier is not intrinsic to these cells but instead is induced by the CNS environment: Stewart and Wiley demonstrated that when avascular tissue from 3-day-old quail brain is transplanted into the coelomic cavity of chick embryos, the chick endothelial cells that vascularize the quail brain grafts form a competent blood-brain barrier; on the other hand, when avascular embryonic quail coelomic grafts are transplanted into embryonic chick brain, the chick endothelial cells that invade the mesenchymal tissue grafts form leaky capillaries and venules. It is, however, not known which cells in the CNS are responsible for inducing endothelial cells to form the tight junctions characteristic of the blood-brain barrier. Astrocytes are the most likely candidates since their processes form endfeet that collectively surround CNS microvessels. In this report we provide direct evidence that astrocytes are capable of inducing blood-brain barrier properties in non-neural endothelial cells in vivo.
            Article 0 comments Cited 194 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Astrocytes regulate myelin clearance through recruitment of microglia during cuprizone-induced demyelination.

              Thomas Skripuletz, Diane Hackstette, Katharina C Bauer … (2013)
              Recent evidence suggests that astrocytes play an important role in regulating de- and remyelination in multiple sclerosis. The role of astrocytes is controversial, and both beneficial as well as detrimental effects are being discussed. We performed loss-of-function studies based on astrocyte depletion in a cuprizone-induced rodent model of demyelination. This led to strong astrogliosis accompanied by microgliosis and demyelination in C57BL/6 wild-type mice. Ablation of astrocytes in glial fibrillary acidic protein-thymidine kinase transgenic mice was associated with a failure of damaged myelin removal and a consecutive delay in remyelination. Despite oligodendrocyte death, myelin was still present, but ultrastructual investigations showed that the myelin structure was loosened and this damaged myelin did not protect axons. These alterations were associated with a decrease in microglial activation. Thus, our results show that astrocyte loss does not prevent myelin damage, but clearance of damaged myelin through recruitment of microglia is impaired. Further studies suggest that this process is regulated by the chemokine CXCL10. As a consequence of the delayed removal of myelin debris, remyelination and oligodendrocyte precursor cell proliferation were impaired. Experiments omitting the influence of myelin debris demonstrated an additional beneficial effect of astrocytes on oligodendrocyte regeneration during remyelination. In conclusion, these data demonstrate for the first time in vivo that astrocytes provide the signal environment that forms the basis for the recruitment of microglia to clear myelin debris, a process required for subsequent repair mechanisms. This is of great importance to understanding regenerative processes in demyelinating diseases such as multiple sclerosis.
              Article 0 comments Cited 136 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                John Shelestak:
                ORCID: http://orcid.org/0000-0001-8766-3461
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: VisualizationRole: Writing – original draft
                Naveen Singhal: Role: MethodologyRole: Supervision
                Lana Frankle: Role: Data curationRole: Investigation
                Riely Tomor: Role: Data curationRole: InvestigationRole: Methodology
                Sarah Sternbach: Role: ConceptualizationRole: MethodologyRole: Resources
                Jennifer McDonough: Role: ConceptualizationRole: Investigation
                Ernest Freeman: Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Supervision
                Robert Clements: Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: SupervisionRole: ValidationRole: Visualization
                Mária A. Deli: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 8 June 2020
                Publication date Collection: 2020
                Volume: 15
                Issue: 6
                Electronic Location Identifier: e0234001
                Affiliations
                [1 ] Department of Biological Sciences, School of Biomedical Sciences, Kent State University, Kent, Ohio, United States of America
                [2 ] Department of Biochemistry, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
                Hungarian Academy of Sciences, HUNGARY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                ‡ These authors also contributed equally to this work.

                Author information
                http://orcid.org/0000-0001-8766-3461
                Article
                Publisher ID: PONE-D-20-02742
                DOI: 10.1371/journal.pone.0234001
                PMC ID: 7279587
                PubMed ID: 32511268
                SO-VID: 0a316e76-de5f-40c0-9be6-84fe69bfe64c
                Copyright © © 2020 Shelestak et al
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 29 January 2020
                Date accepted : 15 May 2020
                Page count
                Figures: 5, Tables: 0, Pages: 17
                Funding
                The author(s) received no specific funding for this work.
                Categories
                Subject: Research Article
                Subject: Biology and Life Sciences
                Subject: Cell Biology
                Subject: Cellular Types
                Subject: Animal Cells
                Subject: Connective Tissue Cells
                Subject: Mast Cells
                Subject: Biology and Life Sciences
                Subject: Anatomy
                Subject: Biological Tissue
                Subject: Connective Tissue
                Subject: Connective Tissue Cells
                Subject: Mast Cells
                Subject: Medicine and Health Sciences
                Subject: Anatomy
                Subject: Biological Tissue
                Subject: Connective Tissue
                Subject: Connective Tissue Cells
                Subject: Mast Cells
                Subject: Biology and Life Sciences
                Subject: Anatomy
                Subject: Brain
                Subject: Corpus Callosum
                Subject: Medicine and Health Sciences
                Subject: Anatomy
                Subject: Brain
                Subject: Corpus Callosum
                Subject: Biology and Life Sciences
                Subject: Anatomy
                Subject: Nervous System
                Subject: Central Nervous System
                Subject: Blood-Brain Barrier
                Subject: Medicine and Health Sciences
                Subject: Anatomy
                Subject: Nervous System
                Subject: Central Nervous System
                Subject: Blood-Brain Barrier
                Subject: Research and Analysis Methods
                Subject: Imaging Techniques
                Subject: Fluorescence Imaging
                Subject: Biology and Life Sciences
                Subject: Cell Biology
                Subject: Cellular Types
                Subject: Animal Cells
                Subject: Glial Cells
                Subject: Macroglial Cells
                Subject: Astrocytes
                Subject: Research and Analysis Methods
                Subject: Specimen Preparation and Treatment
                Subject: Staining
                Subject: Cell Staining
                Subject: Biology and Life Sciences
                Subject: Cell Biology
                Subject: Cellular Types
                Subject: Animal Cells
                Subject: Glial Cells
                Subject: Microglial Cells
                Subject: Research and Analysis Methods
                Subject: Bioassays and Physiological Analysis
                Subject: Cardiovascular Analysis
                Subject: Blood-Brain Barrier Permeability Assay
                Custom metadata
                Data Availability The underlying data for this manuscript is available on Dryad: https://doi.org/10.5061/dryad.dv41ns1vk.

                ScienceOpen disciplines: Uncategorized
                Data availability:
                ScienceOpen disciplines: Uncategorized

                Comments

                Comment on this article

                scite_

                Similar content425

                See all similar

                Cited by14

                See all cited by

                Most referenced authors728

                See all reference authors