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So far, the interaction of psychological stress with TBI not only in the brain but also in peripheral organs is poorly understood. Herein, the impact of acute stress (AS) occurring immediately before TBI is investigated. For this, a mouse model of restraint stress and TBI was employed, and their influence on behavior and gene expression in brain regions, the hypothalamic\u2013pituitary\u2013adrenal (HPA) axis, and peripheral organs was analyzed. Results demonstrate that, compared to single AS or TBI exposure, mice treated with AS prior to TBI showed sex\u2010specific alterations in body weight, memory function, and locomotion. The induction of immediate early genes (IEGs, e.g., c\u2010Fos) by TBI was modulated by previous AS in several brain regions. Furthermore, IEG upregulation along the HPA axis (e.g., pituitary, adrenal glands) and other peripheral organs (e.g., heart) was modulated by AS\u2013TBI interaction. Proteomics of plasma samples revealed proteins potentially mediating this interaction. Finally, the deletion of\n                    <jats:italic>Atf3<\/jats:italic>\n                    diminished the TBI\u2010induced induction of IEGs in peripheral organs but left them largely unaltered in the brain. In summary, AS immediately before brain injury affects the brain and, to a strong degree, also responses in peripheral organs.\n                  <\/jats:p>","DOI":"10.1096\/fj.202301035r","type":"journal-article","created":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T03:16:20Z","timestamp":1696216580000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Acute stress modulates the outcome of traumatic brain injury\u2010associated gene expression and behavioral responses"],"prefix":"10.1096","volume":"37","author":[{"given":"Johanna Christina","family":"Reiners","sequence":"first","affiliation":[{"name":"Institute of Neurobiochemistry Ulm University  Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Leopold","sequence":"additional","affiliation":[{"name":"Institute of Neurobiochemistry Ulm University  Ulm 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