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Blood-Arachnoid Barrier as a Dynamic Physiological and Pharmacological Interface Between Cerebrospinal Fluid and Blood

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Drug Delivery to the Brain

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 33))

Abstract

The blood-arachnoid barrier (BAB) consists of arachnoid epithelial cells linked by tight junctions, and forms one of the interfaces between blood and cerebrospinal fluid (CSF). The BAB was long believed to be impermeable to water-soluble substances and to play a largely passive role until our in vivo studies demonstrated that it is an active interface. Our quantitative proteomic analyses revealed that multiple transporters (OAT1, OAT3, P-gp, BCRP, MATE1, OCT2, PEPT2, etc.) are expressed more abundantly at the BAB than at the blood-cerebrospinal fluid barrier, their membrane localizations are polarized in the BAB, and there are regional differences between the cerebral and spinal cord BAB. These findings would provide a better understanding about the central nervous system kinetics of drugs and endogenous compounds, which cannot be explained by blood-brain and blood-cerebrospinal fluid barriers. Here, we introduce the BAB transport systems and discuss the physiologically and pharmacologically crucial roles of the BAB.

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Abbreviations

BAB:

Blood-arachnoid barrier

BBB:

Blood-brain barrier

BCSFB:

Blood-cerebrospinal fluid barrier

CNS:

Central nervous system

CSF:

Cerebrospinal fluid

LC-MS/MS:

Liquid chromatography-tandem mass spectrometry

qTAP:

Quantitative targeted absolute proteomics

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Acknowledgments

The studies mentioned in this chapter were supported in part by Grants-in-Aids from the Japanese Society for the Promotion of Science (JSPS) for Young Scientists (A) [KAKENHI: 16H06218], Scientific Research (B) [KAKENHI: 17H04004], Bilateral Open Partnership Joint Research Program (between Finland and Japan), Fostering Joint International Research (A) [KAKENHI: 18KK0446], and Early-Career Scientists [KAKENHI: 19 K16438]. This study was also supported in part by Grants-in-Aids from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) for Scientific Research on Innovative Areas [KAKENHI: 18H04534] and from Mochida Memorial Foundation for Medical and Pharmaceutical Research.

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Authors and Affiliations

  1. Division of Membrane Transport and Drug Targeting, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan

    Yasuo Uchida, Ryohei Goto, Takuya Usui, Masanori Tachikawa & Tetsuya Terasaki

  2. Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Japan

    Yasuo Uchida, Takuya Usui, Masanori Tachikawa & Tetsuya Terasaki

Authors
  1. Yasuo Uchida
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  2. Ryohei Goto
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  3. Takuya Usui
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  4. Masanori Tachikawa
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  5. Tetsuya Terasaki
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Corresponding author

Correspondence to Yasuo Uchida .

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Editors and Affiliations

  1. Research Division of Systems Pharmacology and Pharmacy, Leiden University, Leiden, The Netherlands

    Elizabeth C.M. de Lange

  2. Department of Pharmacy, Uppsala University, Uppsala, Sweden

    Margareta Hammarlund-Udenaes

  3. Biology Discovery, Denali Therapeutics, South San Francisco, CA, USA

    Robert G. Thorne

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Uchida, Y., Goto, R., Usui, T., Tachikawa, M., Terasaki, T. (2022). Blood-Arachnoid Barrier as a Dynamic Physiological and Pharmacological Interface Between Cerebrospinal Fluid and Blood. In: de Lange, E.C., Hammarlund-Udenaes, M., Thorne, R.G. (eds) Drug Delivery to the Brain. AAPS Advances in the Pharmaceutical Sciences Series, vol 33. Springer, Cham. https://doi.org/10.1007/978-3-030-88773-5_4

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