dc.contributor.author
Kim, Soo Young
dc.contributor.author
Senatorov, Vladimir V., Jr.
dc.contributor.author
Morrissey, Christapher S.
dc.contributor.author
Lippmann, Kristina
dc.contributor.author
Vazquez, Oscar
dc.contributor.author
Heinemann, Uwe [u.a.]
dc.date.accessioned
2018-06-08T10:26:26Z
dc.date.available
2017-09-08T08:24:48.445Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/20450
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-23753
dc.description.abstract
Brain damage due to stroke or traumatic brain injury (TBI), both leading
causes of serious long-term disability, often leads to the development of
epilepsy. Patients who develop post-injury epilepsy tend to have poor
functional outcomes. Emerging evidence highlights a potential role for blood-
brain barrier (BBB) dysfunction in the development of post-injury epilepsy.
However, common mechanisms underlying the pathological hyperexcitability are
largely unknown. Here, we show that comparative transcriptome analyses predict
remodeling of extracellular matrix (ECM) as a common response to different
types of injuries. ECM-related transcriptional changes were induced by the
serum protein albumin via TGFβ signaling in primary astrocytes. In accordance
with transcriptional responses, we found persistent degradation of protective
ECM structures called perineuronal nets (PNNs) around fast-spiking inhibitory
interneurons, in a rat model of TBI as well as in brains of human epileptic
patients. Exposure of a naïve brain to albumin was sufficient to induce the
transcriptional and translational upregulation of molecules related to ECM
remodeling and the persistent breakdown of PNNs around fast-spiking inhibitory
interneurons, which was contingent on TGFβ signaling activation. Our findings
provide insights on how albumin extravasation that occurs upon BBB dysfunction
in various brain injuries can predispose neural circuitry to the development
of chronic inhibition deficits.
en
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
Blood–brain barrier
dc.subject
Brain injuries
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit
dc.title
TGFβ signaling is associated with changes in inflammatory gene expression and
perineuronal net degradation around inhibitory neurons following various
neurological insults
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
Scientific Reports. - 7 (2017) , Artikel Nr. 7711
dcterms.bibliographicCitation.doi
10.1038/s41598-017-07394-3
dcterms.bibliographicCitation.url
http://www.nature.com/articles/s41598-017-07394-3
refubium.affiliation
Charité - Universitätsmedizin Berlin
de
refubium.mycore.fudocsId
FUDOCS_document_000000027885
refubium.note.author
Der Artikel wurde in einer reinen Open-Access-Zeitschrift publiziert.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000008710
dcterms.accessRights.openaire
open access