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bioRxivNeurosciencePreprint

The nuclear receptor NR4A1 restrains neutrophil granulocyte mediated brain damage in cerebral ischemia

Jan‐Kolja StreckeriD, Marie LiebmanniD, Julian Revenstorff, Carolin BeukeriD, Antje Schmidt‐PogodaiD, Stephanie HuckeiD, Thomas VogliD, Johannes RothiD, Christian ThomasiD, Tanja KuhlmanniD, Heinz WiendliD, Luisa KlotziD, Jens MinnerupiD

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Abstract

Immigration and activation of immune cells play a significant role in damage progression after ischemic stroke. It has been shown that the nuclear receptor NR4A1 exerts a crucial role within the inflammatory response of various immune diseases via regulating immune cell activation. In this study, we investigated the role of NR4A1 on the activation and recruitment of brain resident and peripheral immune cells after cerebral ischemia. Here, we show that NR4A1 mediates an anti-inflammatory and damage limiting effect after ischemic stroke through immigrating neutrophil granulocytes. Importantly, NR4A1-activation with its ligand Cytosporone-B improves functional outcome and diminishes brain damage. Therefore, modulation of NR4A1 is a promising therapeutic target in the treatment of stroke.

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Jan‐Kolja Strecker, Yannick Schmidt, Marie Liebmann+38 more·bioRxiv·Sep 19, 2025· 1 citations