{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T07:19:20Z","timestamp":1787901560327,"version":"build-2784847793"},"reference-count":41,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273984"],"award-info":[{"award-number":["82273984"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2019YFC1708504"],"award-info":[{"award-number":["2019YFC1708504"]}],"id":[{"id":"10.13039\/501100012166","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":[[2026,8]]},"abstract":"ABSTRACT<\/jats:title>\n \n Aims<\/jats:title>\n A stable uptake\u2010release cycle system of dopamine is dependent upon two transporters, dopamine transporter (DAT) and vesicular monoamine transporter (VMAT). Whether the regulation system of dopamine is involved in the neuroprotection mediated by 3\u2010n\u2010butylphthalide (NBP) against ischemic stroke injury is unclear.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Middle cerebral artery occlusion (MCAO) was subjected to evaluate the protection of NBP. In\u00a0vivo microdialysis measurements of neurotransmitters were recorded in the ischemic penumbral area. Brain slices were prepared in MCAO mice to record synaptic function, including miniature excitatory postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs).<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n NBP decreased the infarct size with a dose\u2010dependent manner, and significantly reduced the level of glutamate, while markedly increasing dopamine release. The expressions of DAT and VMAT were significantly decreased by MCAO, which were reversely enhanced by NBP. Pretreatment with VMAT inhibitor, reserpine, abolished the dopamine increase and eliminated the neuroprotection of NBP. The balance between excitatory and inhibitory synaptic transmission is disturbed by ischemic injury and reversed by NBP. Reserpine eliminated the effect of NBP against the disturbance of mEPSCs and mIPSCs. Inhibition of dopamine\u20101 receptor (D\n 1<\/jats:sub>\n R) or adenosine A\n 1<\/jats:sub>\n receptors (A\n 1<\/jats:sub>\n R: downstream of D\n 1<\/jats:sub>\n R) both eliminated the regulation of NBP on the synaptic function and abolished the neuroprotection of NBP.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n The neuroprotective effect of NBP against cerebral ischemic injury may involve the upregulation of the VMAT\u2010DAT\u2010dopamine cycle, which appears to contribute to the amelioration of synaptic dysfunction. The activation of D\n 1<\/jats:sub>\n R and its downstream adenosine A\n 1<\/jats:sub>\n Rs is involved in the neuroprotection mechanism.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/cns.71094","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T05:06:46Z","timestamp":1787116006000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["VMAT<\/scp>\n \u2010\n DAT<\/scp>\n \u2010Dopamine Regulatory System Involved in the Protective Effect of 3\u2010n\u2010Butylphthalide Against Ischemic Stroke"],"prefix":"10.1002","volume":"32","author":[{"given":"Xiao\u2010Ting","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Pharmacy Research, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Shanghai University of Traditional Chinese Medicine Shanghai China"},{"name":"School of Pharmacy Shandong University of Traditional Chinese Medicine Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Research, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Shanghai University of Traditional Chinese Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Chen","sequence":"additional","affiliation":[{"name":"MOE Frontier Center for Brain Science, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruo\u2010Xi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Research, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Shanghai University of Traditional Chinese Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Ling","family":"Su","sequence":"additional","affiliation":[{"name":"Ningbo New Drug Evaluation Center Ningbo China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ding\u2010Feng","family":"Su","sequence":"additional","affiliation":[{"name":"Ningbo New Drug Evaluation Center Ningbo China"},{"name":"Department of Pharmacology Second Military Medical University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3256-644X","authenticated-orcid":false,"given":"Ai\u2010Jun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Research, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Shanghai University of Traditional Chinese Medicine Shanghai China"},{"name":"School of Pharmacy Shandong University of Traditional Chinese Medicine Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"e_1_2_13_2_1","first-page":"e41","article-title":"Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association","volume":"151","author":"Martin S. 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