{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T22:18:07Z","timestamp":1790201887674,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T00:00:00Z","timestamp":1680652800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81871856"],"award-info":[{"award-number":["81871856"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>To explore whether 14, 15\u2010EET regulates mitochondrial dynamics to exert neuroprotective effects after cerebral ischemia\u2013reperfusion and its underlying mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The mouse middle cerebral artery occlusion reperfusion model was used to observe brain infarct volume and neuronal apoptosis by TTC staining and Tunel assay, modified neurological severity score to detect neurological impairment, HE staining and Nissl staining to observe neuron damage, western blot and immunofluorescence methods to detect the expression of mitochondrial dynamics\u2010related proteins, transmission electron microscopy, and Golgi\u2010Cox staining to detect mitochondrial morphology and neuronal dendritic spines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>14, 15\u2010EET reduced the neuronal apoptosis and cerebral infarction volume induced by middle cerebral artery occlusion reperfusion (MCAO\/R), inhibited the degradation of dendritic spines, maintained the structural integrity of neurons, and alleviated neurological impairment. Cerebral ischemia\u2013reperfusion induces mitochondrial dynamics disorders, upregulates the expression of the mitochondrial division protein Fis 1, and inhibits the expression of mitochondrial fusion proteins MFN1, MFN2, and OPA1, while 14, 15\u2010EET treatment reverses this process. Mechanistic studies have shown that 14, 15\u2010EET promotes the phosphorylation of AMPK, upregulates the expression of SIRT1 and phosphorylation of FoxO1, thereby inhibiting mitochondrial division and promoting mitochondrial fusion, preserving mitochondrial dynamics, maintaining neuronal morphological and structural integrity, and alleviating neurological impairment induced by middle cerebral artery occlusion reperfusion. Compound C treatment diminishes the neuroprotective effect of 14, 15\u2010EET following MCAO\/R in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study elucidates the novel neuroprotective mechanism of 14, 15\u2010EET, providing a novel approach for the development of drugs based on mitochondrial dynamics.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.14198","type":"journal-article","created":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T12:35:13Z","timestamp":1680698113000},"page":"2583-2596","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["14, <scp>15\u2010EET<\/scp> alleviates neurological impairment through maintaining mitochondrial dynamics equilibrium via <scp>AMPK<\/scp>\/<scp>SIRT1<\/scp>\/<scp>FoxO1<\/scp> signal pathways in mice with cerebral ischemia reperfusion"],"prefix":"10.1111","volume":"29","author":[{"given":"Jing","family":"Tang","sequence":"first","affiliation":[{"name":"The School of Life Sciences Henan University  475000 Henan Province Kaifeng P. 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