Central Nervous System Stimulants Limit Caffeine Transport at the Blood–Cerebrospinal Fluid Barrier
Caffeine, a common ingredient in energy drinks, crosses the blood–brain barrier easily, but the kinetics of caffeine across the blood–cerebrospinal fluid barrier (BCSFB) has not been investigated. Therefore, 127 autopsy cases (Group A, 30 patients, stimulant-detected group; and Group B, 97 patients,...
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MDPI AG
2022-02-01
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author | Kei Ikeda-Murakami Naoto Tani Tomoya Ikeda Yayoi Aoki Takaki Ishikawa |
author_facet | Kei Ikeda-Murakami Naoto Tani Tomoya Ikeda Yayoi Aoki Takaki Ishikawa |
author_sort | Kei Ikeda-Murakami |
collection | DOAJ |
description | Caffeine, a common ingredient in energy drinks, crosses the blood–brain barrier easily, but the kinetics of caffeine across the blood–cerebrospinal 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. |
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format | Article |
id | doaj.art-34aae358a52c44b4838ef689ae44f376 |
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issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-09T23:43:37Z |
publishDate | 2022-02-01 |
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series | International Journal of Molecular Sciences |
spelling | doaj.art-34aae358a52c44b4838ef689ae44f3762023-11-23T16:47:51ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-02-01233186210.3390/ijms23031862Central Nervous System Stimulants Limit Caffeine Transport at the Blood–Cerebrospinal Fluid BarrierKei Ikeda-Murakami0Naoto Tani1Tomoya Ikeda2Yayoi Aoki3Takaki Ishikawa4Department of Legal Medicine, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno, Osaka 545-8585, JapanDepartment of Legal Medicine, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno, Osaka 545-8585, JapanDepartment of Legal Medicine, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno, Osaka 545-8585, JapanDepartment of Legal Medicine, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno, Osaka 545-8585, JapanDepartment of Legal Medicine, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno, Osaka 545-8585, JapanCaffeine, a common ingredient in energy drinks, crosses the blood–brain barrier easily, but the kinetics of caffeine across the blood–cerebrospinal 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.https://www.mdpi.com/1422-0067/23/3/1862caffeinestimulantsblood–cerebrospinal fluid barrier (BCSFB)BCSFB modelchoroid plexusvacuolation |
spellingShingle | Kei Ikeda-Murakami Naoto Tani Tomoya Ikeda Yayoi Aoki Takaki Ishikawa Central Nervous System Stimulants Limit Caffeine Transport at the Blood–Cerebrospinal Fluid Barrier International Journal of Molecular Sciences caffeine stimulants blood–cerebrospinal fluid barrier (BCSFB) BCSFB model choroid plexus vacuolation |
title | Central Nervous System Stimulants Limit Caffeine Transport at the Blood–Cerebrospinal Fluid Barrier |
title_full | Central Nervous System Stimulants Limit Caffeine Transport at the Blood–Cerebrospinal Fluid Barrier |
title_fullStr | Central Nervous System Stimulants Limit Caffeine Transport at the Blood–Cerebrospinal Fluid Barrier |
title_full_unstemmed | Central Nervous System Stimulants Limit Caffeine Transport at the Blood–Cerebrospinal Fluid Barrier |
title_short | Central Nervous System Stimulants Limit Caffeine Transport at the Blood–Cerebrospinal Fluid Barrier |
title_sort | central nervous system stimulants limit caffeine transport at the blood cerebrospinal fluid barrier |
topic | caffeine stimulants blood–cerebrospinal fluid barrier (BCSFB) BCSFB model choroid plexus vacuolation |
url | https://www.mdpi.com/1422-0067/23/3/1862 |
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