AT 1 inhibition mediated neuroprotection after experimental traumatic brain injury is dependent on neutrophils in male mice.

May 08, 2023

Experts: Ralph Timaru-Kast,Shila P Coronel-Castello,Tobias J Krämer,André V Hugonnet,Michael K E Schäfer,Anne Sebastiani,Serge C Thal

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.
© 2023. The Author(s).

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ABOUT THE EXPERTS

Ralph Timaru-Kast,Shila P Coronel-Castello,Tobias J Krämer,André V Hugonnet,Michael K E Schäfer,Anne Sebastiani,Serge C Thal

Ralph Timaru-Kast

Department of Anesthesiology, University Medical Center of the Johannes Gutenberg-University, Langenbeckstrasse 1, 55131, Mainz, Germany. timaruka@uni-mainz.de.

Shila P Coronel-Castello

Department of Anesthesiology, University Medical Center of the Johannes Gutenberg-University, Langenbeckstrasse 1, 55131, Mainz, Germany.

Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg-University, Langenbeckstrasse 1, 55131, Mainz, Germany.

Tobias J Krämer

Department of Anesthesiology, University Medical Center of the Johannes Gutenberg-University, Langenbeckstrasse 1, 55131, Mainz, Germany.

Faculty of Health, University of Witten/Herdecke, Alfred-Herrhausen-Strasse 50, 58455, Witten, Germany.

André V Hugonnet

Department of Anesthesiology, University Medical Center of the Johannes Gutenberg-University, Langenbeckstrasse 1, 55131, Mainz, Germany.

Michael K E Schäfer

Department of Anesthesiology, University Medical Center of the Johannes Gutenberg-University, Langenbeckstrasse 1, 55131, Mainz, Germany.

Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg-University, Langenbeckstrasse 1, 55131, Mainz, Germany.

Anne Sebastiani

Department of Anesthesiology, University Medical Center of the Johannes Gutenberg-University, Langenbeckstrasse 1, 55131, Mainz, Germany.

Department of Anesthesiology, HELIOS University Hospital Wuppertal, University of Witten/Herdecke, Heusnerstrasse 40, 42283, Wuppertal, Germany.

Serge C Thal

Department of Anesthesiology, University Medical Center of the Johannes Gutenberg-University, Langenbeckstrasse 1, 55131, Mainz, Germany.

Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg-University, Langenbeckstrasse 1, 55131, Mainz, Germany.

Department of Anesthesiology, HELIOS University Hospital Wuppertal, University of Witten/Herdecke, Heusnerstrasse 40, 42283, Wuppertal, Germany.