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Neuroprotective Mechanisms at the Blood-CSF Barrier of the Developing and Adult Brain

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Role of the Choroid Plexus in Health and Disease

Part of the book series: Physiology in Health and Disease ((PIHD))

Abstract

In addition to CSF secretion, the choroid plexuses fulfill neuroendocrine, neuroimmune and neuroprotective functions. Choroidal neuroprotection results from a combination of tight junctions that prevent the paracellular passage of blood-borne compounds into the CSF, efflux transporters that reduce the CSF bioavailability of numerous potentially toxic drugs and other xenobiotics, and metabolizing enzymes that detoxify reactive organic molecules and reactive oxygen species. The choroid plexuses display developmental stage-specific neuroprotective properties that are reviewed in this chapter.

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Notes

  1. 1.

    Capitalized characters are used when referring to human transporters or to transporters listed in a general context. Minor characters are used when specifically referring to rodent transporters.

References

  • Benarroch EE (2016) Choroid plexus--CSF system: recent developments and clinical correlations. Neurology 86:286–296

    Article  PubMed  Google Scholar 

  • Crossgrove JS, Li GJ, Zheng W (2005) The choroid plexus removes beta-amyloid from brain cerebrospinal fluid. Exp Biol Med (Maywood) 230:771–776

    Article  CAS  Google Scholar 

  • Demeestere D, Libert C, Vandenbroucke RE (2015) Therapeutic implications of the choroid plexus-cerebrospinal fluid interface in neuropsychiatric disorders. Brain Behav Immun 50:1–13

    Article  PubMed  Google Scholar 

  • Drake JM, Sainte-Rose C, DaSilva M, Hirsch JF (1991) Cerebrospinal fluid flow dynamics in children with external ventricular drains. Neurosurgery 28:242–250

    Article  CAS  PubMed  Google Scholar 

  • Duan H, Wang J (2013) Impaired monoamine and organic cation uptake in choroid plexus in mice with targeted disruption of the plasma membrane monoamine transporter (Slc29a4) gene. J Biol Chem 288:3535–3544

    Article  CAS  PubMed  Google Scholar 

  • Dziegielewska KM, Ek J, Habgood MD, Saunders NR (2001) Development of the choroid plexus. Microsc Res Tech 52:5–20

    Article  CAS  PubMed  Google Scholar 

  • Ek CJ, Dziegielewska KM, Stolp H, Saunders NR (2006) Functional effectiveness of the blood-brain barrier to small water-soluble molecules in developing and adult opossum (Monodelphis domestica). J Comp Neurol 496:13–26

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gazzin S, Strazielle N, Schmitt C, Fevre-Montange M, Ostrow JD, Tiribelli C, Ghersi-Egea JF (2008) Differential expression of the multidrug resistance-related proteins ABCb1 and ABCc1 between blood-brain interfaces. J Comp Neurol 510:497–507

    Article  CAS  PubMed  Google Scholar 

  • Ghersi-Egea JF, Damkier HH (2017) Blood–brain interfaces organization in relation to inorganic ion transport, CSF secretion, and circulation. In: Badaut J, Plesnila N (eds) Brain edema. Academic, Oxford, pp 29–48

    Chapter  Google Scholar 

  • Ghersi-Egea JF, Leninger-Muller B, Suleman G, Siest G, Minn A (1994) Localization of drug-metabolizing enzyme activities to blood-brain interfaces and circumventricular organs. J Neurochem 62:1089–1096

    Article  CAS  PubMed  Google Scholar 

  • Ghersi-Egea JF, Leininger-Muller B, Cecchelli R, Fenstermacher JD (1995) Blood-brain interfaces: relevance to cerebral drug metabolism. Toxicol Lett 82-83:645–653

    Article  CAS  PubMed  Google Scholar 

  • Ghersi-Egea JF, Strazielle N, Murat A, Jouvet A, Buenerd A, Belin MF (2006) Brain protection at the blood-cerebrospinal fluid interface involves a glutathione-dependent metabolic barrier mechanism. J Cereb Blood Flow Metab 26:1165–1175

    Article  CAS  PubMed  Google Scholar 

  • Ghersi-Egea JF, Saudrais E, Strazielle N (2018a) Barriers to drug distribution into the perinatal and postnatal brain. Pharm Res 35:84

    Article  PubMed  CAS  Google Scholar 

  • Ghersi-Egea JF, Strazielle N, Catala M, Silva-Vargas V, Doetsch F, Engelhardt B (2018b) Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease. Acta Neuropathol 135:337–361

    Article  CAS  PubMed  Google Scholar 

  • Gitto E, Reiter RJ, Karbownik M, Tan DX, Gitto P, Barberi S, Barberi I (2002) Causes of oxidative stress in the pre- and perinatal period. Biol Neonate 81:146–157

    Article  CAS  PubMed  Google Scholar 

  • Johanson CE, Duncan JA 3rd, Klinge PM, Brinker T, Stopa EG, Silverberg GD (2008) Multiplicity of cerebrospinal fluid functions: new challenges in health and disease. Cerebrospinal Fluid Res 5:10

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kaur C, Rathnasamy G, Ling EA (2016) The choroid plexus in healthy and diseased brain. J Neuropathol Exp Neurol 75:198–213

    Article  CAS  PubMed  Google Scholar 

  • Kratzer I, Vasiljevic A, Rey C, Fevre-Montange M, Saunders N, Strazielle N, Ghersi-Egea JF (2012) Complexity and developmental changes in the expression pattern of claudins at the blood-CSF barrier. Histochem Cell Biol 138:861–879

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kratzer I, Liddelow SA, Saunders NR, Dziegielewska KM, Strazielle N, Ghersi-Egea JF (2013) Developmental changes in the transcriptome of the rat choroid plexus in relation to neuroprotection. Fluids Barriers CNS 10:25

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kratzer I, Strazielle N, Saudrais E, Monkkonen K, Malleval C, Blondel S, Ghersi-Egea JF (2018) Glutathione conjugation at the blood-CSF barrier efficiently prevents exposure of the developing brain fluid environment to blood-borne reactive electrophilic substances. J Neurosci 38:3466–3479

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lauer AN, Tenenbaum T, Schroten H, Schwerk C (2018) The diverse cellular responses of the choroid plexus during infection of the central nervous system. Am J Physiol Cell Physiol 314:C152–C165

    Article  PubMed  CAS  Google Scholar 

  • Leggas M, Adachi M, Scheffer GL, Sun D, Wielinga P, Du G, Mercer KE, Zhuang Y, Panetta JC, Johnston B, Scheper RJ, Stewart CF, Schuetz JD (2004) Mrp4 confers resistance to topotecan and protects the brain from chemotherapy. Mol Cell Biol 24:7612–7621

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leininger-Muller B, Ghersi-Egea JF, Siest G, Minn A (1994) Induction and immunological characterization of the uridine diphosphate-glucuronosyltransferase conjugating 1-naphthol in the rat choroid plexus. Neurosci Lett 175:37–40

    Article  CAS  PubMed  Google Scholar 

  • Liddelow SA, Dziegielewska KM, Ek CJ, Habgood MD, Bauer H, Bauer HC, Lindsay H, Wakefield MJ, Strazielle N, Kratzer I, Mollgard K, Ghersi-Egea JF, Saunders NR (2013) Mechanisms that determine the internal environment of the developing brain: a transcriptomic, functional and ultrastructural approach. PLoS One 8:e65629

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lun MP, Monuki ES, Lehtinen MK (2015) Development and functions of the choroid plexus-cerebrospinal fluid system. Nat Rev Neurosci 16:445–457

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marques F, Sousa JC, Brito MA, Pahnke J, Santos C, Correia-Neves M, Palha JA (2017) The choroid plexus in health and in disease: dialogues into and out of the brain. Neurobiol Dis 107:32–40

    Article  PubMed  Google Scholar 

  • Mollgard K, Dziegielewska KM, Holst CB, Habgood MD, Saunders NR (2017) Brain barriers and functional interfaces with sequential appearance of ABC efflux transporters during human development. Sci Rep 7:11603

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Motohashi H, Inui K (2013) Multidrug and toxin extrusion family SLC47: physiological, pharmacokinetic and toxicokinetic importance of MATE1 and MATE2-K. Mol Asp Med 34:661–668

    Article  CAS  Google Scholar 

  • Praetorius J, Damkier HH (2017) Transport across the choroid plexus epithelium. Am J Physiol Cell Physiol 312:C673–C686

    Article  PubMed  Google Scholar 

  • Prochiantz A, Fuchs J, Di Nardo AA (2014) Postnatal signalling with homeoprotein transcription factors. Philos Trans R Soc Lond Ser B Biol Sci 369(1652):20130518. https://doi.org/10.1098/rstb.2013.0518

    Article  CAS  Google Scholar 

  • Richard K, Hume R, Kaptein E, Stanley EL, Visser TJ, Coughtrie MW (2001) Sulfation of thyroid hormone and dopamine during human development: ontogeny of phenol sulfotransferases and arylsulfatase in liver, lung, and brain. J Clin Endocrinol Metab 86:2734–2742

    CAS  PubMed  Google Scholar 

  • Saudrais E, Strazielle N, Ghersi-Egea JF (2018) Choroid plexus glutathione peroxidases are instrumental in protecting the brain fluid environment from hydroperoxides during postnatal development. Am J Physiol Cell Physiol 315:C445–C456

    Article  CAS  PubMed  Google Scholar 

  • Saunders NR, Dziegielewska KM, Mollgard K, Habgood MD, Wakefield MJ, Lindsay H, Stratzielle N, Ghersi-Egea JF, Liddelow SA (2015) Influx mechanisms in the embryonic and adult rat choroid plexus: a transcriptome study. Front Neurosci 9:123

    PubMed  PubMed Central  Google Scholar 

  • Schlachetzki F, Zhu C, Pardridge WM (2002) Expression of the neonatal fc receptor (FcRn) at the blood-brain barrier. J Neurochem 81:203–206

    Article  CAS  PubMed  Google Scholar 

  • Spector R, Keep RF, Robert Snodgrass S, Smith QR, Johanson CE (2015) A balanced view of choroid plexus structure and function: focus on adult humans. Exp Neurol 267:78–86

    Article  PubMed  Google Scholar 

  • Steinemann A, Galm I, Chip S, Nitsch C, Maly IP (2016) Claudin-1, −2 and −3 are selectively expressed in the epithelia of the choroid plexus of the mouse from early development and into adulthood while Claudin-5 is restricted to endothelial cells. Front Neuroanat 10:16

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Storck SE, Pietrzik CU (2017) Endothelial LRP1 - a potential target for the treatment of Alzheimer’s disease : theme: drug discovery, development and delivery in Alzheimer’s disease guest editor: Davide Brambilla. Pharm Res 34:2637–2651

    Article  CAS  PubMed  Google Scholar 

  • Strazielle N, Ghersi-Egea JF (1999) Demonstration of a coupled metabolism-efflux process at the choroid plexus as a mechanism of brain protection toward xenobiotics. J Neurosci 19:6275–6289

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Strazielle N, Ghersi-Egea JF (2013) Physiology of blood-brain interfaces in relation to brain disposition of small compounds and macromolecules. Mol Pharm 10:1473–1491

    Article  CAS  PubMed  Google Scholar 

  • Strazielle N, Ghersi-Egea JF (2015) Efflux transporters in blood-brain interfaces of the developing brain. Front Neurosci 9:21

    Article  PubMed  PubMed Central  Google Scholar 

  • Strazielle N, Ghersi-Egea JF (2016) Potential pathways for CNS drug delivery across the blood-cerebrospinal fluid barrier. Curr Pharm Des 22:5463–5476

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Strazielle N, Khuth ST, Ghersi-Egea JF (2004) Detoxification systems, passive and specific transport for drugs at the blood-CSF barrier in normal and pathological situations. Adv Drug Deliv Rev 56:1717–1740

    Article  CAS  PubMed  Google Scholar 

  • Tayarani I, Cloez I, Clement M, Bourre JM (1989) Antioxidant enzymes and related trace elements in aging brain capillaries and choroid plexus. J Neurochem 53:817–824

    Article  CAS  PubMed  Google Scholar 

  • Tietz S, Engelhardt B (2015) Brain barriers: crosstalk between complex tight junctions and adherens junctions. J Cell Biol 209:493–506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Torres-Cuevas I, Parra-Llorca A, Sanchez-Illana A, Nunez-Ramiro A, Kuligowski J, Chafer-Pericas C, Cernada M, Escobar J, Vento M (2017) Oxygen and oxidative stress in the perinatal period. Redox Biol 12:674–681

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tsuchiya K, Hayashida T, Hamada A, Kato S, Oka S, Gatanaga H (2014) Low raltegravir concentration in cerebrospinal fluid in patients with ABCG2 genetic variants. J Acquir Immune Defic Syndr 66:484–486

    Article  CAS  PubMed  Google Scholar 

  • Uchida Y, Zhang Z, Tachikawa M, Terasaki T (2015) Quantitative targeted absolute proteomics of rat blood-cerebrospinal fluid barrier transporters: comparison with a human specimen. J Neurochem 134:1104–1115

    Article  CAS  PubMed  Google Scholar 

  • Usui T, Nakazawa A, Okura T, Deguchi Y, Akanuma SI, Kubo Y, Hosoya KI (2016) Histamine elimination from the cerebrospinal fluid across the blood-cerebrospinal fluid barrier: involvement of plasma membrane monoamine transporter (PMAT/SLC29A4). J Neurochem 139:408–418

    Article  CAS  PubMed  Google Scholar 

  • Virag J, Haberler C, Baksa G, Piurko V, Hegedus Z, Reiniger L, Balint K, Chocholous M, Kiss A, Lotz G, Glasz T, Schaff Z, Garami M, Hegedus B (2017) Region specific differences of claudin-5 expression in pediatric intracranial ependymomas: potential prognostic role in Supratentorial cases. Pathol Oncol Res 23:245–252

    Article  CAS  PubMed  Google Scholar 

  • Wilson C, Munoz-Palma E, Gonzalez-Billault C (2018) From birth to death: a role for reactive oxygen species in neuronal development. Semin Cell Dev Biol 80:43–49

    Article  CAS  PubMed  Google Scholar 

  • Yasuda T, Tomita T, McLone DG, Donovan M (2002) Measurement of cerebrospinal fluid output through external ventricular drainage in one hundred infants and children: correlation with cerebrospinal fluid production. Pediatr Neurosurg 36:22–28

    Article  PubMed  Google Scholar 

  • Zhang Z, Uchida Y, Hirano S, Ando D, Kubo Y, Auriola S, Akanuma SI, Hosoya KI, Urtti A, Terasaki T, Tachikawa M (2017) Inner blood-retinal barrier dominantly expresses breast cancer resistance protein: comparative quantitative targeted absolute proteomics study of CNS barriers in pig. Mol Pharm 14:3729–3738

    Article  CAS  PubMed  Google Scholar 

  • Zhang Z, Tachikawa M, Uchida Y, Terasaki T (2018) Drug clearance from cerebrospinal fluid mediated by organic anion transporters 1 (Slc22a6) and 3 (Slc22a8) at arachnoid membrane of rats. Mol Pharm 15:911–922

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by ANR-10-IBHU-0003 CESAME.

Author information

Authors and Affiliations

  1. FLUID Team, Lyon Neurosciences Research Center, INSERM U1028, CNRS UMR5292, Lyon1 University, Lyon, France

    Jean-Francois Ghersi-Egea, Alexandre Vasiljevic & Nathalie Strazielle

  2. BIP Facility, Lyon Neurosciences Research Center, Lyon, France

    Sandrine Blondel

  3. Brain-i, Lyon, France

    Nathalie Strazielle

Authors
  1. Jean-Francois Ghersi-Egea
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  2. Alexandre Vasiljevic
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  3. Sandrine Blondel
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  4. Nathalie Strazielle
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Corresponding author

Correspondence to Jean-Francois Ghersi-Egea .

Editor information

Editors and Affiliations

  1. Department of Biomedicine, Faculty of Health, Aarhus University, Aarhus, Denmark

    Jeppe Praetorius

  2. Department of Biology, Indiana University – Purdue University Indianapolis, Indianapolis, IN, USA

    Bonnie Blazer-Yost

  3. Department of Biomedicine, Faculty of Health, Aarhus University, Aarhus, Denmark

    Helle Damkier

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Ghersi-Egea, JF., Vasiljevic, A., Blondel, S., Strazielle, N. (2020). Neuroprotective Mechanisms at the Blood-CSF Barrier of the Developing and Adult Brain. In: Praetorius, J., Blazer-Yost, B., Damkier, H. (eds) Role of the Choroid Plexus in Health and Disease. Physiology in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-0716-0536-3_8

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