Authors:	Timaru-Kast, Ralph Coronel-Castello, Shila P. Krämer, Tobias J. Hugonnet, André V. Schäfer, Michael K. E. Sebastiani, Anne Thal, Serge C.
Title:	AT 1 inhibition mediated neuroprotection after experimental traumatic brain injury is dependent on neutrophils in male mice
Online publication date:	24-Jan-2024
Year of first publication:	2023
Language:	english
Abstract:	After traumatic brain injury (TBI) cerebral inflammation with invasion of neutrophils and lymphocytes is a crucial factor in the process of secondary brain damage. In TBI the intrinsic renin-angiotensin system is an important mediator of cerebral inflammation, as inhibition of the angiotensin II receptor type 1 (AT1) reduces secondary brain damage and the invasion of neutrophil granulocytes into injured cerebral tissue. The current study explored the involvement of immune cells in neuroprotection mediated by AT1 inhibition following experimental TBI. Four different cohorts of male mice were examined, investigating the effects of neutropenia (anti-Ly6G antibody mediated neutrophil depletion; C57BL/6), lymphopenia (RAG1 deficiency, RAG1−/−), and their combination with candesartan-mediated AT1 inhibition. The present results showed that reduction of neutrophils and lymphocytes, as well as AT1 inhibition in wild type and RAG1−/− mice, reduced brain damage and neuroinflammation after TBI. However, in neutropenic mice, candesartan did not have an effect. Interestingly, AT1 inhibition was found to be neuroprotective in RAG1−/− mice but not in neutropenic mice. The findings suggest that AT1 inhibition may exert neuroprotection by reducing the inflammation caused by neutrophils, ultimately leading to a decrease in their invasion into cerebral tissue.
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-9967
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 13
Pages or article number:	7413
Publisher:	Macmillan Publishers Limited, part of Springer Nature
Publisher place:	London
Issue date:	2023
ISSN:	2045-2322
Publisher DOI:	10.1038/s41598-023-33797-6
Appears in collections:	DFG-491381577-G