{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T15:37:50Z","timestamp":1792683470537,"version":"4.5.0"},"reference-count":52,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T00:00:00Z","timestamp":1729728000000},"content-version":"vor","delay-in-days":23,"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":[[2024,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Temporal lobe epilepsy (TLE), a prevalent chronic neurological disorder, affects millions of individuals and is often resistant to anti\u2010epileptic drugs. Increasing evidence has shown that acetylcholine (ACh) and cholinergic neurotransmission play a role in the pathophysiology of epilepsy. Tropisetron, an antiemetic drug used for chemotherapy in clinic, has displayed potential in the treatment of Alzheimer's disease, depression, and schizophrenia in animal models. However, as a partial agonist of \u03b17 nicotinic acetylcholine receptors (\u03b17nAChRs), whether tropisetron possesses the therapeutic potential for TLE has not yet been determined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, tropisetron was intraperitoneally injected into pilocarpine\u2010induced epileptic rats for 3\u2009weeks. Alpha\u2010bungarotoxin (\u03b1\u2010bgt), a specific \u03b17nAChR antagonist, was applied to investigate the mechanism of tropisetron. Rats were assessed for spontaneous recurrent seizures (SRS) and cognitive function using video surveillance and Morris's water maze testing. Hippocampal impairment and synaptic structure were evaluated by Nissl staining, immunohistochemistry, and Golgi staining. Additionally, the levels of glutamate, \u03b3\u2010aminobutyric acid (GABA), ACh, \u03b17nAChRs, neuroinflammatory cytokines, glucocorticoids and their receptors, as well as synapse\u2010associated protein (F\u2010actin, cofilin\u20101) were quantified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The results showed that tropisetron significantly reduced SRS, improved cognitive function, alleviated hippocampal sclerosis, and concurrently suppressed synaptic remodeling and the m<jats:sup>6<\/jats:sup>A modification of cofilin\u20101 in TLE rats. Furthermore, tropisetron lowered glutamate levels without affecting GABA levels, reduced neuroinflammation, and increased ACh levels and \u03b17nAChR expression in the hippocampi of TLE rats. The effects of tropisetron treatment were counteracted by \u03b1\u2010bgt.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In summary, these findings indicate that tropisetron exhibits an anti\u2010epileptic effect and provides neuroprotection in TLE rats through the activation of \u03b17nAChRs. The potential mechanism may involve the reduction of glutamate levels, enhancement of cholinergic transmission, and suppression of synaptic remodeling. Consequently, the present study not only highlights the potential of tropisetron as an anti\u2010epileptic drug but also identifies \u03b17nAChRs as a promising therapeutic target for the treatment of TLE.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.70086","type":"journal-article","created":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T12:11:04Z","timestamp":1729771864000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Tropisetron, an Antiemetic Drug, Exerts an Anti\u2010Epileptic Effect Through the Activation of <scp>\u03b17nAChRs<\/scp> in a Rat Model of Temporal Lobe Epilepsy"],"prefix":"10.1111","volume":"30","author":[{"given":"Xu","family":"Qian","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy, School of Pharmaceutical Guangzhou Medical University and Key Laboratory of Molecular Target &amp;Clinical Pharmacology  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinwen","family":"Sheng","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, School of Pharmaceutical Guangzhou Medical University and Key Laboratory of Molecular Target &amp;Clinical Pharmacology  Guangzhou China"},{"name":"Department of Pharmacy The First Affiliated Hospital of Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiqiang","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Six Affiliated Hospital (Dongguan Eastern Central Hospital) Jinan University  Dongguan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zulipiya","family":"Yiming","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, School of Pharmaceutical Guangzhou Medical University and Key Laboratory of Molecular Target &amp;Clinical Pharmacology  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjun","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, School of Pharmaceutical Guangzhou Medical University and Key Laboratory of Molecular Target &amp;Clinical Pharmacology  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiagui","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Six Affiliated Hospital (Dongguan Eastern Central Hospital) Jinan University  Dongguan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tengyue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, School of Pharmaceutical Guangzhou Medical University and Key Laboratory of Molecular Target &amp;Clinical Pharmacology  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, School of Pharmaceutical Guangzhou Medical University and Key Laboratory of Molecular Target &amp;Clinical Pharmacology  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuqiao","family":"He","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, School of Pharmaceutical Guangzhou Medical University and Key Laboratory of Molecular Target &amp;Clinical Pharmacology  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Six Affiliated Hospital (Dongguan Eastern Central Hospital) Jinan University  Dongguan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4983-4343","authenticated-orcid":false,"given":"Mei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, School of Pharmaceutical Guangzhou Medical University and Key Laboratory of Molecular Target &amp;Clinical Pharmacology  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(18)32596\u20100"},{"key":"e_1_2_9_3_1","volume-title":"Mesial Temporal Lobe Epilepsy","author":"Nayak C. 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