Central Nervous System Stimulants Limit Caffeine Transport at the Blood–Cerebrospinal Fluid Barrier

Ikeda-Murakami, Kei; Tani, Naoto; Ikeda, Tomoya; Aoki, Yayoi; Ishikawa, Takaki

doi:10.3390/ijms23031862

Cited by 5 publications

(3 citation statements)

References 49 publications

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“…Our model showed that CAF and CBZ have high permeabilities, and LP and CET showed low permeability. These results are consistent with previous studies using animal or cell-culture models [25,27,37,38]. CAF is a well-known positive control for simple diffusion across the BBB, and it showed high permeability in both blood and brain channels in our model.…”

Section: Discussionsupporting

confidence: 93%

Evaluation of Drug Blood-Brain-Barrier Permeability Using a Microfluidic Chip

Yang,

Shin,

Jeong

et al. 2024

Pharmaceutics

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The blood-brain-barrier (BBB) is made up of blood vessels whose permeability enables the passage of some compounds. A predictive model of BBB permeability is important in the early stages of drug development. The predicted BBB permeabilities of drugs have been confirmed using a variety of in vitro methods to reduce the quantities of drug candidates needed in preclinical and clinical trials. Most prior studies have relied on animal or cell-culture models, which do not fully recapitulate the human BBB. The development of microfluidic models of human-derived BBB cells could address this issue. We analyzed a model for predicting BBB permeability using the Emulate BBB-on-a-chip machine. Ten compounds were evaluated, and their permeabilities were estimated. Our study demonstrated that the permeability trends of ten compounds in our microfluidic-based system resembled those observed in previous animal and cell-based experiments. Furthermore, we established a general correlation between the partition coefficient ( and the apparent permeability (). In conclusion, we introduced a new paradigm for predicting BBB permeability using microfluidic-based systems.

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Section: Discussionsupporting

confidence: 93%

Evaluation of Drug Blood-Brain-Barrier Permeability Using a Microfluidic Chip

Yang,

Shin,

Jeong

et al. 2024

Pharmaceutics

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“…When crossing the BBB, certain bio-chemical properties are favourable: lipophilicity (fat-solubility), small physical size, a molecular weight below 450 g/mol, and low hydrogen-bonding potential (meaning the molecule exists at a neutral charge at a physiological pH of 7.5). Caffeine falls into the small molecule category, with a molecular weight of 194 g/mol, and demonstrates amphipathicity, allowing it to cross the BBB using passive transport (Figure 1) [14,15].…”

Section: Mechanism Of Caffeine Transport Across the Bbbmentioning

confidence: 99%

The Physiological, Cognitive, and Developmental Effects of Prenatal Caffeine Consumption on Foetal Pregnancy Outcomes

Patel,

Burow

2023

URNCST Journal

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Introduction: Maternal caffeine consumption during pregnancy may confer developmental risk to the foetus due to caffeine’s ability to cross the blood brain barrier (BBB) and blood placental barrier (BPB). This literature review investigated caffeine’s properties and mechanism of passage through the BBB and BPB. The subsequent effects of moderate-to-excessive maternal caffeine consumption (≥ 200mg of caffeine daily) on physical development, cognition, and behaviour were further explored. Methods: The review was conducted using PubMED, NCBI, and Google Scholar, using key terms such as “pregnancy”, “caffeine”, “prenatal”, “adverse effect”, “development”, and “embryo development”. Articles selected were published within the last 15 years (2008-2023) and longitudinal studies, cohort studies, and experimental methods using animal models were included. Results: It was found prenatal caffeine exposure poses a variety of potential consequences for the infant prior to and after delivery. Notably, physical developmental risks include fetal growth restriction, birth defect(s), and changes in neuronal structure and blood flow. Cognitive and behavioural consequences include possible links to externalizing behaviour problems, decreased intelligence quotient (IQ), attentive deficit and hyperactivity disorder (ADHD), and autism spectrum disorder (ASD) during childhood. Discussion: This research is primarily restricted to animal models and cohort studies. Moroever, there were several conflicting conclusions surrounding behavioural and cognitive effects of prenatal caffeine exposure. This drives inquiry into how further research can both solidify causal relationships and be conducted ethically to help inform parents about the potential risks of prenatal caffeine exposure. Conclusion: With a global trend of increasing caffeine consumption, through coffee, black tea, and recently, matcha, this review provided insight into this ever-growing aspect of our lifestyles. It is paramount to understand the effect of caffeine on foetuses to promote safe and healthy pregnancy outcomes.

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“…Caffeine (1,3,7-trimethylxanthine, CAF), a plant alkaloid structurally related to adenosine, exerts numerous physiological and pharmacological effects on many organs, including the cardiovascular, renal, respiratory, and central nervous systems (Persad, 2011). Caffeine readily crosses the bloodbrain barrier located in cerebral microvascular endothelial cells and the blood-cerebrospinal fluid barrier located in the epithelial cells of the choroid plexus (ChP) (McCall et al, 1982;Ikeda-Murakami et al, 2022). In the brain, caffeine exerts most of its biological effects by antagonising adenosine receptors (ADORs) and, like adenosine, affects neurons and glial cells of all brain areas (Ribeiro and Sebastião, 2010).…”

Section: Introductionmentioning

confidence: 99%