{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:31:40Z","timestamp":1783557100568,"version":"3.55.0"},"reference-count":45,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T00:00:00Z","timestamp":1753401600000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Neuroinflammation constitutes a critical pathological event subsequent to ischemic stroke. AD16, a novel anti\u2010neuroinflammatory compound, has demonstrated efficacy in alleviating neuroinflammation in neonatal rats induced by ischemia\u2013hypoxia. This study aims to elucidate the therapeutic utility and underlying mechanisms of AD16 in an adult ischemic stroke rat model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A rat transient middle cerebral artery occlusion (tMCAO) model was employed. Neurological function was evaluated using the Longa and Garcia JH scores, motor function was assessed through rotary rod and CatWalk gait analysis, and brain injury was examined via TTC and Nissl staining. Molecular docking techniques simulate the binding of a target compound to a potential target. Western blot, immunofluorescence, and enzyme\u2010linked immunosorbent assay (ELISA) were used to detect microglia phenotype, pro\u2010inflammatory factors, and activation of signaling molecules.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>AD16 treatment improved neural function in tMCAO rats, reduced cerebral infarction volume and brain water content, preserved blood\u2013brain barrier integrity, and inhibited pro\u2010inflammatory cytokines. Molecular docking showed AD16 has high affinity for \u03b17nAChR, TLR4, ERK, and STAT3. AD16 increased \u03b17nAChR, CD206, and p\u2010ERK protein levels, while decreasing CD40, CD68, TLR4, and p\u2010STAT3. These effects were reversed by \u03b1\u2010BTX (\u03b17nAChR inhibitor) and U0126 (ERK inhibitor).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>AD16 may inhibit microglia activation and polarization via the \u03b17nAChR\u2010ERK\u2010STAT3 pathway, thus reducing neuroinflammation from cerebral ischemia and protecting the brain. This study suggests AD16 as a potential treatment for ischemic stroke.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.70519","type":"journal-article","created":{"date-parts":[[2025,7,26]],"date-time":"2025-07-26T06:29:02Z","timestamp":1753511342000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["AD16 Modulates Microglial Activation and Polarization to Mitigate Neuroinflammation in Ischemic Stroke Models Through \u03b17nAChR\u2010ERK\u2010STAT3 Signaling"],"prefix":"10.1111","volume":"31","author":[{"given":"Guo\u2010Jian","family":"Zhao","sequence":"first","affiliation":[{"name":"Jiangxi Province Key Laboratory of Pharmacology of Traditional Chinese Medicine, Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education, Ganzhou Key Laboratory of Neuroinflammation Research Gannan Medical University  Ganzhou China"},{"name":"College of Physical Education and Health 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