Please use this identifier to cite or link to this item:
http://doi.org/10.25358/openscience-8673
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 |
ROR: | https://ror.org/023b0x485 |
DOI: | http://doi.org/10.25358/openscience-8673 |
Version: | Published version |
Publication type: | Zeitschriftenaufsatz |
Document type specification: | Scientific article |
License: | CC BY |
Information on rights of use: | https://creativecommons.org/licenses/by/4.0/ |
Journal: | Scientific reports 12 |
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 |
Files in This Item:
File | Description | Size | Format | ||
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![]() | at2_activation_does_not_influ-20230126122430391.pdf | 1.1 MB | Adobe PDF | View/Open |