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However, the underlying mechanisms linking central immune cells and neurons to sepsis\u2010induced cardiomyopathy remain to be clarified. Here, acute sepsis is induced by cecal ligation puncture (CLP), and pharmacological and RNAi interventions are administered to the thoracic spinal cord via intrathecal injection. Echocardiography and histology confirm reduced cardiac function following CLP. Sepsis\u2010induced spinal cord changes involved neuronal activation and loss with decreased gamma\u2010aminobutyric acid (GABA) levels. Necroptosis effector genes are markedly upregulated with increased RIPK1, RIPK3, and MLKL co\u2010expression evident in spinal GABAergic neurons, while administration of the necroptosis inhibitor Necrostatin\u20101 substantially preserves neurons and reverses sepsis\u2010associated cardiac functional changes. Sepsis triggers increased C3, IL\u20106 and TNF\u2010\u03b1 in spinal astrocytes, while administration of the \u03b12A\u2010adrenergic receptor (\u03b12\u2010AR) agonist dexmedetomidine blocked inflammatory factor production, neuronal damage, and cardiac dysfunction. These findings suggest that sepsis\u2010induced cardiomyopathy arises from a neuroimmune interplay involving spinal astrocyte activation, GABAergic neuronal necroptosis, and cardiac damage driven by sympathetic hyperstimulation.<\/jats:p>","DOI":"10.1002\/advs.202504406","type":"journal-article","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T05:59:03Z","timestamp":1753163943000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Activation of Spinal Astrocyte \u03b12A Adrenoceptors Protects Against Sepsis\u2010Induced Heart Injury Through Inhibition of GABAergic Neuronal Necroptosis"],"prefix":"10.1002","volume":"12","author":[{"given":"Ruilin","family":"He","sequence":"first","affiliation":[{"name":"Department of Anesthesiology The First Affiliated Hospital of Anhui Medical University Key Laboratory of Anesthesia and Perioperative Medicine of Anhui Higher Education Institutes Anhui Medical University  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