{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:41:23Z","timestamp":1791999683392,"version":"4.4.0"},"reference-count":114,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Development of Science and Technology of Jilin Province","award":["YDZJ202601ZYTS314"],"award-info":[{"award-number":["YDZJ202601ZYTS314"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hypertension is the leading global risk factor for cardiovascular diseases, and its pathogenesis is closely linked to excessive sympathetic activation, which markedly elevates the risk of stroke, heart failure and other adverse cardiovascular events. Traditional therapies mainly target peripheral mechanisms, whereas the clinical efficacy of renal denervation highlights the critical role of central regulation in sympathetic hyperactivity. This review focuses on the core sympathetic nuclei including the rostral ventrolateral medulla (RVLM) and paraventricular nucleus (PVN), with epigenetic regulation as a key innovative perspective. We systematically summarize the upstream driving effects of reactive oxygen species (ROS) and neuroinflammation, and emphasize lncRNA\/miRNA-mediated post-transcriptional regulation and the modulatory actions of gasotransmitters. Under stress conditions, aberrant activation of ROS and neuroimmune pathways, epigenetic reprogramming, and hyperexcitability of central sympathetic neurons act as key events in sympathetic overactivation, which interact synergistically to promote hypertension. Integrating evidence from multiple hypertensive animal models and clinical studies, we discuss multimodal interventions including pharmacotherapy, nanozyme biotechnology and neuromodulation, analyze current translational challenges, and provide a theoretical framework for developing central-targeted antihypertensive therapies.<\/jats:p>","DOI":"10.3390\/ijms27094063","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T06:50:01Z","timestamp":1777618201000},"page":"4063","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Central Sympathetic Nerve Activation-Mediated Hypertension: Target Mechanisms and Multimodal Interventions\u2014From Basic Research to Clinical Translation"],"prefix":"10.3390","volume":"27","author":[{"given":"Bo","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Biotechnology, School of Life Science, Jilin Normal University, Siping 136000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2685-2722","authenticated-orcid":false,"given":"Yi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, School of Life Science, Jilin Normal University, Siping 136000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0058-6219","authenticated-orcid":false,"given":"Renjun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, School of Life Science, Jilin Normal University, Siping 136000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2308","DOI":"10.1002\/alz.12707","article-title":"Hypertension and Alzheimer\u2019s disease pathology at autopsy: A systematic review","volume":"18","author":"Abdulrahman","year":"2022","journal-title":"Alzheimers Dement."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Goorani, S., Zangene, S., and Imig, J.D. 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