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Authors: Timaru-Kast, Ralph
Bardon, Andreas Garcia
Luh, Clara
Coronel-Castello, Shila P.
Songarj, Phuripong
Griemert, Eva-Verena
Krämer, Tobias J.
Sebastiani, Anne
Steckelings, Ulrike Muscha
Thal, Serge C.
Title: AT2 activation does not influence brain damage in the early phase after experimental traumatic brain injury in male mice
Online publication date: 10-Feb-2023
Year of first publication: 2022
Language: english
Abstract: Antagonism of the angiotensin II type 1 receptor (AT1) improves neurological function and reduces brain damage after experimental traumatic brain injury (TBI), which may be partly a result of enhanced indirect angiotensin II type 2 receptor (AT2) stimulation. AT2 stimulation was demonstrated to be neuroprotective via anti-inflammatory, vasodilatory, and neuroregenerative mechanisms in experimental cerebral pathology models. We recently demonstrated an upregulation of AT2 after TBI suggesting a protective mechanism. The present study investigated the effect of post-traumatic (5 days after TBI) AT2 activation via high and low doses of a selective AT2 agonist, compound 21 (C21), compared to vehicle-treated controls. No differences in the extent of the TBI-induced lesions were found between both doses of C21 and the controls. We then tested AT2-knockdown animals for secondary brain damage after experimental TBI. Lesion volume and neurological outcomes in AT2-deficient mice were similar to those in wild-type control mice at both 24 h and 5 days post-trauma. Thus, in contrast to AT1 antagonism, AT2 modulation does not influence the initial pathophysiological mechanisms of TBI in the first 5 days after the insult, indicating that AT2 plays only a minor role in the early phase following trauma-induced brain damage.
DDC: 610 Medizin
610 Medical sciences
Institution: Johannes Gutenberg-Universität Mainz
Department: FB 04 Medizin
Place: Mainz
Version: Published version
Publication type: Zeitschriftenaufsatz
Document type specification: Scientific article
License: CC BY
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Journal: Scientific reports
Pages or article number: 14280
Publisher: Macmillan Publishers Limited, part of Springer Nature
Publisher place: London
Issue date: 2022
ISSN: 2045-2322
Publisher DOI: 10.1038/s41598-022-18338-x
Appears in collections:DFG-491381577-G

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