{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T20:43:02Z","timestamp":1788381782549,"version":"build-2803163510"},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T00:00:00Z","timestamp":1673568000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Fracture in acute stage of ischemic stroke can increase inflammatory response and enhance stroke injury. Loganin alleviates the symptoms of many inflammatory diseases through its anti\u2010inflammatory effect, but its role in ischemic stroke and fracture remains to be explored. Here, mice were handled with permanent middle cerebral artery occlusion (pMCAO) followed by tibial fracture 1\u2009day later to establish a pMCAO+fracture model. Loganin or Methyllycaconitine (MLA, a specific a7nAchR inhibitor) were intragastrically administered 2 or 0.5\u00a0h before pMCAO, respectively. And mouse motor function and infarct volume were evaluated 3\u2009days after pMCAO. We found that loganin alleviated the neurological deficit, cerebral infarction volume, and neuronal apoptosis (NeuN\n                    <jats:sup>+<\/jats:sup>\n                    TUNEL\n                    <jats:sup>+<\/jats:sup>\n                    ) in mice with pMCAO+fracture. And loganin suppressed pMCAO+fracture\u2010induced neuroinflammation by promoting M2 microglia polarization (Iba1\n                    <jats:sup>+<\/jats:sup>\n                    CD206\n                    <jats:sup>+<\/jats:sup>\n                    ) and inhibiting M1 microglia polarization (Iba1\n                    <jats:sup>+<\/jats:sup>\n                    CD11b\n                    <jats:sup>+<\/jats:sup>\n                    ). While administration with MLA reversed the protective effect of loganin on pMCAO+fracture\u2010induced neurological deficit and neuroinflammation. Next, LPS was used to stimulate BV2 microglia to simulate pMCAO+fracture\u2010induced inflammatory microenvironment in vitro. Loganin facilitated the transformation of LPS\u2010stimulated BV2 cells from M1 pro\u2010inflammatory state (CD11b\n                    <jats:sup>+<\/jats:sup>\n                    ) to M2 anti\u2010inflammatory state (CD206\n                    <jats:sup>+<\/jats:sup>\n                    ), which was antagonized by treatment with MLA. And loganin induced autophagy activation in LPS\u2010stimulated BV2 cells by activating a7nAchR. Moreover, treatment with rapamycin (an autophagy activator) neutralized the inhibitory effect of MLA on loganin induced transformation of BV2 cells to M2 phenotype. Furthermore, BV2 cells were treated with LPS, LPS\u2009+\u2009loganin, LPS\u2009+\u2009loganin+MLA, or LPS\u2009+\u2009loganin+MLA+ rapamycin to obtain conditioned medium (CM) for stimulating primary neurons. Loganin reduced the damage of primary neurons caused by LPS\u2010stimulated BV2 microglia through activating a7nAchR and inducing autophagy activation. In conclusion, loganin played anti\u2010inflammatory and neuroprotective roles in pMCAO + fracture mice by activating a7nAchR, enhancing autophagy and promoting M2 polarization of microglia.\n                  <\/jats:p>","DOI":"10.1002\/tox.23738","type":"journal-article","created":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T12:36:21Z","timestamp":1673613381000},"page":"926-940","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Loganin attenuates neuroinflammation after ischemic stroke and fracture by regulating\n                    <scp>\u03b17nAChR<\/scp>\n                    \u2010mediated microglial polarization"],"prefix":"10.1002","volume":"38","author":[{"given":"Kang","family":"Huo","sequence":"first","affiliation":[{"name":"Department of Neurology the First Affiliated Hospital of Xi'an Jiaotong University  Xi'an Shaanxi Province People's Republic of China"},{"name":"Center of brain health The First 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