{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T22:19:31Z","timestamp":1790029171738,"version":"4.0.1"},"reference-count":51,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T00:00:00Z","timestamp":1644192000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Caffeine, a common ingredient in energy drinks, crosses the blood\u2013brain barrier easily, but the kinetics of caffeine across the blood\u2013cerebrospinal fluid barrier (BCSFB) has not been investigated. Therefore, 127 autopsy cases (Group A, 30 patients, stimulant-detected group; and Group B, 97 patients, no stimulant detected group) were examined. In addition, a BCSFB model was constructed using human vascular endothelial cells and human choroid plexus epithelial cells separated by a filter, and the kinetics of caffeine in the BCSFB and the effects of 4-aminopyridine (4-AP), a neuroexcitatory agent, were studied. Caffeine concentrations in right heart blood (Rs) and cerebrospinal fluid (CSF) were compared in the autopsy cases: caffeine concentrations were higher in Rs than CSF in Group A compared to Group B. In the BCSFB model, caffeine and 4-AP were added to the upper layer, and the concentration in the lower layer of choroid plexus epithelial cells was measured. The CSF caffeine concentration was suppressed, depending on the 4-AP concentration. Histomorphological examination suggested that choroid plexus epithelial cells were involved in inhibiting the efflux of caffeine to the CSF. Thus, the simultaneous presence of stimulants and caffeine inhibits caffeine transfer across the BCSFB.<\/jats:p>","DOI":"10.3390\/ijms23031862","type":"journal-article","created":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T08:38:48Z","timestamp":1644223128000},"page":"1862","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Central Nervous System Stimulants Limit Caffeine Transport at the Blood\u2013Cerebrospinal Fluid Barrier"],"prefix":"10.3390","volume":"23","author":[{"given":"Kei","family":"Ikeda-Murakami","sequence":"first","affiliation":[{"name":"Department of Legal Medicine, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoto","family":"Tani","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno, Osaka 545-8585, Japan"},{"name":"Forensic Autopsy Section, Medico-Legal Consultation and Postmortem Investigation Support Center, c\/o Department of Legal Medicine, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoya","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno, Osaka 545-8585, Japan"},{"name":"Forensic Autopsy Section, Medico-Legal Consultation and Postmortem Investigation Support Center, c\/o Department of Legal Medicine, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8378-0174","authenticated-orcid":false,"given":"Yayoi","family":"Aoki","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaki","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno, Osaka 545-8585, Japan"},{"name":"Forensic Autopsy Section, Medico-Legal Consultation and Postmortem Investigation Support Center, c\/o Department of Legal Medicine, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1002\/bdr2.1177","article-title":"Taurine, caffeine, and energy drinks: Reviewing the risks to the adolescent brain","volume":"109","author":"Curran","year":"2017","journal-title":"Birth Defects Res."},{"key":"ref_2","first-page":"55","article-title":"Two fatal cases of caffeine poisoning and a review of the literature","volume":"34","author":"Fujihara","year":"2017","journal-title":"Shimane J. 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