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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Main Authors: Kei Ikeda-Murakami, Naoto Tani, Tomoya Ikeda, Yayoi Aoki, Takaki Ishikawa
Format: Article
Language:English
Published: MDPI AG 2022-02-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/3/1862
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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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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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