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  1. AU="Reddy, Avril"
  2. AU="Vachani, Anil"
  3. AU="Lofland, Gabriela"
  4. AU="Zou, Xiaoyan"
  5. AU="Norhafizah Bt Sahril"

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  1. Article ; Online: Mosaic deletion of claudin-5 reveals rapid non-cell-autonomous consequences of blood-brain barrier leakage.

    Vázquez-Liébanas, Elisa / Mocci, Giuseppe / Li, Weihan / Laviña, Bàrbara / Reddy, Avril / O'Connor, Claire / Hudson, Natalie / Elbeck, Zaher / Nikoloudis, Ioannis / Gaengel, Konstantin / Vanlandewijck, Michael / Campbell, Matthew / Betsholtz, Christer / Mäe, Maarja Andaloussi

    Cell reports

    2024  Volume 43, Issue 3, Page(s) 113911

    Abstract: Claudin-5 (CLDN5) is an endothelial tight junction protein essential for blood-brain barrier (BBB) formation. Abnormal CLDN5 expression is common in brain disease, and knockdown of Cldn5 at the BBB has been proposed to facilitate drug delivery to the ... ...

    Abstract Claudin-5 (CLDN5) is an endothelial tight junction protein essential for blood-brain barrier (BBB) formation. Abnormal CLDN5 expression is common in brain disease, and knockdown of Cldn5 at the BBB has been proposed to facilitate drug delivery to the brain. To study the consequences of CLDN5 loss in the mature brain, we induced mosaic endothelial-specific Cldn5 gene ablation in adult mice (Cldn5
    MeSH term(s) Animals ; Mice ; Biological Transport ; Blood-Brain Barrier/metabolism ; Brain/metabolism ; Claudin-5/genetics ; Claudin-5/metabolism ; Endothelial Cells/metabolism
    Chemical Substances Claudin-5 ; Cldn5 protein, mouse
    Language English
    Publishing date 2024-03-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2024.113911
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Microvascular stabilization via blood-brain barrier regulation prevents seizure activity.

    Greene, Chris / Hanley, Nicole / Reschke, Cristina R / Reddy, Avril / Mäe, Maarja A / Connolly, Ruairi / Behan, Claire / O'Keeffe, Eoin / Bolger, Isobel / Hudson, Natalie / Delaney, Conor / Farrell, Michael A / O'Brien, Donncha F / Cryan, Jane / Brett, Francesca M / Beausang, Alan / Betsholtz, Christer / Henshall, David C / Doherty, Colin P /
    Campbell, Matthew

    Nature communications

    2022  Volume 13, Issue 1, Page(s) 2003

    Abstract: Blood-brain barrier (BBB) dysfunction is associated with worse epilepsy outcomes however the underlying molecular mechanisms of BBB dysfunction remain to be elucidated. Tight junction proteins are important regulators of BBB integrity and in particular, ... ...

    Abstract Blood-brain barrier (BBB) dysfunction is associated with worse epilepsy outcomes however the underlying molecular mechanisms of BBB dysfunction remain to be elucidated. Tight junction proteins are important regulators of BBB integrity and in particular, the tight junction protein claudin-5 is the most enriched in brain endothelial cells and regulates size-selectivity at the BBB. Additionally, disruption of claudin-5 expression has been implicated in numerous disorders including schizophrenia, depression and traumatic brain injury, yet its role in epilepsy has not been fully deciphered. Here we report that claudin-5 protein levels are significantly diminished in surgically resected brain tissue from patients with treatment-resistant epilepsy. Concomitantly, dynamic contrast-enhanced MRI in these patients showed widespread BBB disruption. We show that targeted disruption of claudin-5 in the hippocampus or genetic heterozygosity of claudin-5 in mice exacerbates kainic acid-induced seizures and BBB disruption. Additionally, inducible knockdown of claudin-5 in mice leads to spontaneous recurrent seizures, severe neuroinflammation, and mortality. Finally, we identify that RepSox, a regulator of claudin-5 expression, can prevent seizure activity in experimental epilepsy. Altogether, we propose that BBB stabilizing drugs could represent a new generation of agents to prevent seizure activity in epilepsy patients.
    MeSH term(s) Animals ; Blood-Brain Barrier/metabolism ; Claudin-5/genetics ; Claudin-5/metabolism ; Endothelial Cells/metabolism ; Humans ; Mice ; Seizures/metabolism ; Tight Junction Proteins/metabolism ; Tight Junctions/metabolism
    Chemical Substances Claudin-5 ; Tight Junction Proteins
    Language English
    Publishing date 2022-04-14
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-29657-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

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