Clostridium perfringens Epsilon Toxin Compromises the Blood-Brain Barrier in a Humanized Zebrafish Model
dc.contributor.author | Adler, D | |
dc.contributor.author | Linden, JR | |
dc.contributor.author | Shetty, SV | |
dc.contributor.author | Ma, Y | |
dc.contributor.author | Bokori-Brown, M | |
dc.contributor.author | Titball, RW | |
dc.contributor.author | Vartanian, T | |
dc.date.accessioned | 2019-08-27T08:58:25Z | |
dc.date.issued | 2019-04-11 | |
dc.description.abstract | Clostridium perfringens epsilon toxin (ETX) is hypothesized to mediate blood-brain barrier (BBB) permeability by binding to the myelin and lymphocyte protein (MAL) on the luminal surface of endothelial cells (ECs). However, the kinetics of this interaction and a general understanding of ETX's behavior in a live organism have yet to be appreciated. Here we investigate ETX binding and BBB breakdown in living Danio rerio (zebrafish). Wild-type zebrafish ECs do not bind ETX. When zebrafish ECs are engineered to express human MAL (hMAL), proETX binding occurs in a time-dependent manner. Injection of activated toxin in hMAL zebrafish initiates BBB leakage, hMAL downregulation, blood vessel stenosis, perivascular edema, and blood stasis. We propose a kinetic model of MAL-dependent ETX binding and neurovascular pathology. By generating a humanized zebrafish BBB model, this study contributes to our understanding of ETX-induced BBB permeability and strengthens the proposal that MAL is the ETX receptor. | en_GB |
dc.description.sponsorship | National Institute of Neurological Disorders and Stroke | en_GB |
dc.description.sponsorship | Wilma S. and Laurence A. Tisch Foundation | en_GB |
dc.identifier.citation | Vol. 15, pp. 39 - 54 | en_GB |
dc.identifier.doi | 10.1016/j.isci.2019.04.016 | |
dc.identifier.grantnumber | 1R01NS104350 | en_GB |
dc.identifier.grantnumber | 1R21MS106581 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/38447 | |
dc.language.iso | en | en_GB |
dc.publisher | Elsevier (Cell Press) | en_GB |
dc.rights | © 2019 The Authors. Open access under a Creative Commons licence: https://creativecommons.org/licenses/by-nc-nd/4.0/ | en_GB |
dc.subject | Pathogenic Organism | en_GB |
dc.subject | Vascular Remodeling | en_GB |
dc.subject | Molecular Mechanism of Behavior | en_GB |
dc.subject | Model Organism | en_GB |
dc.title | Clostridium perfringens Epsilon Toxin Compromises the Blood-Brain Barrier in a Humanized Zebrafish Model | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2019-08-27T08:58:25Z | |
dc.description | This is the final version. Available on open access from Elsevier vis the DOI in this record | en_GB |
dc.identifier.eissn | 2589-0042 | |
dc.identifier.journal | iScience | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | en_GB |
dcterms.dateAccepted | 2019-04-08 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2019-05-31 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2019-08-27T08:55:11Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2019-08-27T08:58:28Z | |
refterms.panel | A | en_GB |
refterms.depositException | publishedGoldOA |
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