The choroid plexus (CP) forming the blood-cerebrospinal fluid (B-CSF) barrier is among the least studied structures of the central nervous system (CNS) despite its clinical importance. The CP is an epithelio-endothelial convolute comprising a highly vascularized stroma with fenestrated capillaries and a continuous lining of epithelial cells joined by apical tight junctions (TJs) that are crucial in forming the B-CSF barrier. Integrity of the CP is critical for maintaining brain homeostasis and B-CSF barrier permeability. Recent experimental and clinical research has uncovered the significance of the CP in the pathophysiology of various diseases affecting the CNS. The CP is involved in penetration of various pathogens into the CNS, as well as the development of neurodegenerative (e.g., Alzheimer´s disease) and autoimmune diseases (e.g., multiple sclerosis). Moreover, the CP was shown to be important for restoring brain homeostasis following stroke and trauma. In addition, new diagnostic methods and treatment of CP papilloma and carcinoma have recently been developed. This review describes and summarizes the current state of knowledge with regard to the roles of the CP and B-CSF barrier in the pathophysiology of various types of CNS diseases and sets up the foundation for further avenues of research.

Department of Anatomy Cellular and Molecular Neurobiology Research Group Faculty of Medicine Masaryk University CZ 625 00 Brno Czech Republic

Department of Neurosurgery Faculty of Medicine Masaryk University and St Anne´s University Hospital Brno Pekařská 53 CZ 656 91 Brno Czech Republic

Zobrazit více v PubMed

Abbott NJ, Patabendige AAK, Dolman DEM, Yusof SR, Begley DJ. Structure and function of the blood–brain barrier. Neurobiol Dis. 2010;37:13–25. doi: 10.1016/j.nbd.2009.07.030. PubMed DOI

Hladky SB, Barrand MA. Mechanisms of fluid movement into, through and out of the brain: evaluation of the evidence. Fluids Barriers CNS. 2014;11:26. doi: 10.1186/2045-8118-11-26. PubMed DOI PMC

Johanson CE, Duncan JA, Stopa EG, Baird A. Enhanced prospects for drug delivery and brain targeting by the choroid plexus–CSF route. Pharm Res. 2005;22:1011–1037. doi: 10.1007/s11095-005-6039-0. PubMed DOI

Bors L, Tóth K, Tóth EZ, Bajza Á, Csorba A, Szigeti K, et al. Age-dependent changes at the blood–brain barrier. A comparative structural and functional study in young adult and middle aged rats. Brain Res Bull. 2018;139:269–277. doi: 10.1016/j.brainresbull.2018.03.001. PubMed DOI

Huber JD, Egleton RD, Davis TP. Molecular physiology and pathophysiology of tight junctions in the blood–brain barrier. Trends Neurosci. 2001;24:719–725. doi: 10.1016/s0166-2236(00)02004-x. PubMed DOI

Parikh V, Tucci V, Galwankar S. Infections of the nervous system. Int J Crit Illn Inj Sci. 2012;2:82–97. doi: 10.4103/2229-5151.97273. PubMed DOI PMC

Zhao Z, Nelson AR, Betsholtz C, Zlokovic BV. Establishment and dysfunction of the blood–brain barrier. Cell. 2015;163:1064–1078. doi: 10.1016/j.cell.2015.10.067. PubMed DOI PMC

Redzic Z, Segal M. The structure of the choroid plexus and the physiology of the choroid plexus epithelium. Adv Drug Deliv Rev. 2004;56:1695–1716. doi: 10.1016/j.addr.2004.07.005. PubMed DOI

Sarin H. Physiologic upper limits of pore size of different blood capillary types and another perspective on the dual pore theory of microvascular permeability. J Angiogenes Res. 2010;2:14. doi: 10.1186/2040-2384-2-14. PubMed DOI PMC

Strazielle N, Ghersi-Egea JF. Choroid plexus in the central nervous system: biology and physiopathology. J Neuropathol Exp Neurol. 2000;59:561–574. doi: 10.1093/jnen/59.7.561. PubMed DOI

Wolburg H, Paulus W. Choroid plexus: biology and pathology. Acta Neuropathol. 2010;119:75–88. doi: 10.1007/s00401-009-0627-8. PubMed DOI

Carpenter SJ, McCarthy LE, Borison HL. Electron microscopic study of the epiplexus (Kolmer) cells of the cat choroid plexus. Z Zellforsch Mikrosk Anat. 1970;110:471–486. doi: 10.1007/bf00330099. PubMed DOI

Hosoya Y, Fujita T. Scanning electron microscope observation of intraventricular macrophages (Kolmer Cells) in the rat brain. Archiv Histol Japn. 1973;35:133–140. doi: 10.1679/aohc1950.35.133. PubMed DOI

Maslieieva V, Thompson RJ. A critical role for pannexin-1 in activation of innate immune cells of the choroid plexus. Channels. 2014;8:131–141. doi: 10.4161/chan.27653. PubMed DOI PMC

Quintela T, Albuquerque T, Lundkvist G, Carmine Belin A, Talhada D, Gonçalves I, et al. The choroid plexus harbors a circadian oscillator modulated by estrogens. Chronobiol Int. 2018;35:270–279. doi: 10.1080/07420528.2017.1400978. PubMed DOI

Santos CRA, Duarte AC, Costa AR, Tomás J, Quintela T, Gonçalves I. The senses of the choroid plexus. Prog Neurobiol. 2019;182:101680. doi: 10.1016/j.pneurobio.2019.101680. PubMed DOI

Spector R, Keep RF, Robert Snodgrass S, Smith QR, Johanson CE. A balanced view of choroid plexus structure and function: focus on adult humans. Exp Neurol. 2015;267:78–86. doi: 10.1016/j.expneurol.2015.02.032. PubMed DOI

Damkier HH, Brown PD, Praetorius J. Cerebrospinal fluid secretion by the choroid plexus. Physiol Rev. 2013;93:1847–1892. doi: 10.1152/physrev.00004.2013. PubMed DOI

Hladky SB, Barrand MA. Fluid and ion transfer across the blood–brain and blood–cerebrospinal fluid barriers; a comparative account of mechanisms and roles. Fluids Barriers CNS. 2016;13:19. doi: 10.1186/s12987-016-0040-3. PubMed DOI PMC

Praetorius J, Damkier HH. Transport across the choroid plexus epithelium. Am J Physiol Cell Physiol. 2017;312:C673–C686. doi: 10.1152/ajpcell.00041.2017. PubMed DOI

Ghersi-Egea J-F, Strazielle N, Catala M, Silva-Vargas V, Doetsch F, Engelhardt B. Molecular anatomy and functions of the choroidal blood–cerebrospinal fluid barrier in health and disease. Acta Neuropathol. 2018;135:337–361. doi: 10.1007/s00401-018-1807-1. PubMed DOI

Milhorat TH, Hammock MK, Fenstermacher JD, Levin VA. Cerebrospinal fluid production by the choroid plexus and brain. Science. 1971;173:330–332. doi: 10.1126/science.173.3994.330. PubMed DOI

Segal MB, Pollay M. The secretion of cerebrospinal fluid. Exp Eye Res. 1977;25(Suppl 1):127–148. doi: 10.1016/s0014-4835(77)80012-2. PubMed DOI

Redzic ZB, Preston JE, Duncan JA, Chodobski A, Szmydynger-Chodobska J. The choroid plexus-cerebrospinal fluid system: from development to aging. Curr Topics Dev Biol. 2005;71:1–52. doi: 10.1016/s0070-2153(05)71001-2. PubMed DOI

Rosenberg GA, Kyner WT, Estrada E. Bulk flow of brain interstitial fluid under normal and hyperosmolar conditions. Am J Physiol. 1980;238:F42–F49. doi: 10.1152/ajprenal.1980.238.1.f42. PubMed DOI

Sakka L, Coll G, Chazal J. Anatomy and physiology of cerebrospinal fluid. Eur Ann Otorhinolaryngol Head Neck Dis. 2011;128:309–316. doi: 10.1016/j.anorl.2011.03.002. PubMed DOI

Wright EM. Transport processes in the formation of the cerebrospinal fluid. Rev Physiol Biochem Pharmacol. 1978;83:1–34. doi: 10.1007/3-540-08907-1_1. PubMed DOI

Bairamian D, Johanson CE, Parmelee JT, Epstein MH. Potassium cotransport with sodium and chloride in the choroid plexus. J Neurochem. 1991;56:1623–1629. doi: 10.1111/j.1471-4159.1991.tb02060.x. PubMed DOI

Brown PD, Davies SL, Speake T, Millar ID. Molecular mechanisms of cerebrospinal fluid production. Neuroscience. 2004;129:957–970. doi: 10.1016/j.neuroscience.2004.07.003. PubMed DOI PMC

Kotera T, Brown PD. Evidence for two types of potassium current in rat choroid plexus epithelial cells. Pflugers Arch. 1994;427:317–324. doi: 10.1007/bf00374540. PubMed DOI

Pollay M, Hisey B, Reynolds E, Tomkins P, Stevens FA, Smith R. Choroid plexus Na+/K+-activated adenosine triphosphatase and cerebrospinal fluid formation. Neurosurgery. 1985;17:768–772. doi: 10.1227/00006123-198511000-00007. PubMed DOI

Praetorius J. Water and solute secretion by the choroid plexus. Pflugers Arch Eur J Physiol. 2007;454:1–18. doi: 10.1007/s00424-006-0170-6. PubMed DOI

Speake T, Whitwell C, Kajita H, Majid A, Brown PD. Mechanisms of CSF secretion by the choroid plexus. Microsc Res Tech. 2001;52:49–59. doi: 10.1002/1097-0029(20010101)52:1<49::aid-jemt7>3.0.co;2-c. PubMed DOI

Zeuthen T, Wright EM. Epithelial potassium transport: tracer and electrophysiological studies in choroid plexus. J Membrain Biol. 1981;60:105–128. doi: 10.1007/bf01870414. PubMed DOI

Zlokovic BV, Mackic JB, Wang L, McComb JG, McDonough A. Differential expression of Na, K-ATPase alpha and beta subunit isoforms at the blood–brain barrier and the choroid plexus. J Biol Chem. 1993;268:8019–8025. PubMed

Cornford EM, Hyman S, Cornford ME, Damian RT. Glut1 glucose transporter in the primate choroid plexus endothelium. J Neuropathol Exp Neurol. 1998;57:404–414. doi: 10.1097/00005072-199805000-00004. PubMed DOI

Steffensen AB, Oernbo EK, Stoica A, Gerkau NJ, Barbuskaite D, Tritsaris K, et al. Cotransporter-mediated water transport underlying cerebrospinal fluid formation. Nat Commun. 2018;9:2167. doi: 10.1038/s41467-018-04677-9. PubMed DOI PMC

Patyal P, Alvarez-Leefmans FJ. Expression of NKCC1 and aquaporins 4, 7 and 9 in mouse choroid plexus and ependymal cells. FASEB J. 2016;30:lb621.

Praetorius J, Nielsen S. Distribution of sodium transporters and aquaporin-1 in the human choroid plexus. Am J Physiol Cell Physiol. 2006;291:C59–C67. doi: 10.1152/ajpcell.00433.2005. PubMed DOI

Nielsen S, Smith BL, Christensen EI, Agre P. Distribution of the aquaporin CHIP in secretory and resorptive epithelia and capillary endothelia. PNAS. 1993;90:7275–7279. doi: 10.1073/pnas.90.15.7275. PubMed DOI PMC

Masseguin C, Corcoran M, Carcenac C, Daunton NG, Güell A, Verkman AS, et al. Altered gravity downregulates aquaporin-1 protein expression in choroid plexus. J Appl Physiol. 2000;88:843–850. doi: 10.1152/jappl.2000.88.3.843. PubMed DOI

Oshio K, Watanabe H, Song Y, Verkman AS, Manley GT. Reduced cerebrospinal fluid production and intracranial pressure in mice lacking choroid plexus water channel Aquaporin-1. FASEB J. 2005;19:76–78. doi: 10.1096/fj.04-1711fje. PubMed DOI

Longatti PL, Basaldella L, Orvieto E, Fiorindi A, Carteri A. Choroid plexus and aquaporin-1: a novel explanation of cerebrospinal fluid production. Pediatr Neurosurg. 2004;40:277–283. doi: 10.1159/000083740. PubMed DOI

Nazari Z, Nabiuni M, Safaei Nejad Z, Delfan B, Irian S. Expression of aquaporins in the rat choroid plexus. Archiv Neurosci. 2014;2:e17312. doi: 10.5812/archneurosci.17312. DOI

Speake T, Freeman LJ, Brown PD. Expression of aquaporin 1 and aquaporin 4 water channels in rat choroid plexus. Biochim Biophys Acta. 2003;1609:80–86. doi: 10.1016/s0005-2736(02)00658-2. PubMed DOI

Edvinsson L, Nielsen KC, Owman C, West KA. Adrenergic innervation of the mammalian choroid plexus. Am J Anat. 1974;139:299–307. doi: 10.1002/aja.1001390302. DOI

Vogh BP, Godman DR. Timolol plus acetazolamide: effect on formation of cerebrospinal fluid in cats and rats. Can J Physiol Pharmacol. 1985;63:340–343. doi: 10.1139/y85-061. PubMed DOI

Lindvall M, Owman C. Autonomic nerves in the mammalian choroid plexus and their influence on the formation of cerebrospinal fluid. J Cereb Blood Flow Metab. 1981;1:245–266. doi: 10.1038/jcbfm.1981.30. PubMed DOI

Lindvall M, Edvinsson L, Owman C. Histochemical study on regional differences in the cholinergic nerve supply of the choroid plexus from various laboratory animals. Exp Neurol. 1977;55:152–159. doi: 10.1016/0014-4886(77)90166-2. PubMed DOI

Ellis DZ, Nathanson JA, Sweadner KJ. Carbachol inhibits Na(+)-K(+)-ATPase activity in choroid plexus via stimulation of the NO/cGMP pathway. Am J Physiol Cell Physiol. 2000;279:C1685–C1693. doi: 10.1152/ajpcell.2000.279.6.c1685. PubMed DOI

Moskowitz MA, Liebmann JE, Reinhard JF, Schlosberg A. Raphe origin of serotonin-containing neurons within choroid plexus of the rat. Brain Res. 1979;169:590–594. doi: 10.1016/0006-8993(79)90410-4. PubMed DOI

Lindvall M, Alumets J, Edvinsson L, Fahrenkrug J, Håkanson R, Hanko J, et al. Peptidergic (VIP) nerves in the mammalian choroid plexus. Neurosci Lett. 1978;9:77–82. doi: 10.1016/0304-3940(78)90051-4. PubMed DOI

Ghersi-Egea J-F, Strazielle N. Choroid plexus transporters for drugs and other xenobiotics. J Drug Target. 2002;10:353–357. doi: 10.1080/10611860290031859. PubMed DOI

Borst P, Evers R, Kool M, Wijnholds J. The multidrug resistance protein family. Biochim Biophys Acta. 1999;1461:347–357. doi: 10.1016/s0005-2736(99)00167-4. PubMed DOI

Wijnholds J, deLange EC, Scheffer GL, van den Berg DJ, Mol CA, van der Valk M, et al. Multidrug resistance protein 1 protects the choroid plexus epithelium and contributes to the blood–cerebrospinal fluid barrier. J Clin Invest. 2000;105:279–285. doi: 10.1172/jci8267. PubMed DOI PMC

Nishino J, Suzuki H, Sugiyama D, Kitazawa T, Ito K, Hanano M, et al. Transepithelial transport of organic anions across the choroid plexus: possible involvement of organic anion transporter and multidrug resistance-associated protein. J Pharmacol Exp Ther. 1999;290:289–294. PubMed

Rao VV, Dahlheimer JL, Bardgett ME, Snyder AZ, Finch RA, Sartorelli AC, et al. Choroid plexus epithelial expression of MDR1 P glycoprotein and multidrug resistance-associated protein contribute to the blood–cerebrospinal-fluid drug-permeability barrier. PNAS. 1999;96:3900–3905. doi: 10.1073/pnas.96.7.3900. PubMed DOI PMC

Sun H, Dai H, Shaik N, Elmquist WF. Drug efflux transporters in the CNS. Adv Drug Deliv Rev. 2003;55:83–105. doi: 10.1016/s0169-409x(02)00172-2. PubMed DOI

Banks WA. Delivery of peptides to the brain: emphasis on therapeutic development. Pept Sci. 2008;90:589–594. doi: 10.1002/bip.20980. PubMed DOI

Daneman R. The blood–brain barrier in health and disease. Ann Neurol. 2012;72:648–672. doi: 10.1002/ana.23648. PubMed DOI

Preusser M, Berghoff AS, Thallinger C, Zielinski C. CECOG educational illustrations: the blood–brain barrier and its relevance for targeted cancer therapies and immuno-oncology. ESMO Open. 2017;2:e000194. doi: 10.1136/esmoopen-2017-000194. PubMed DOI PMC

Tournier N, Decleves X, Saubamea B, Scherrmann J-M, Cisternino S. Opioid transport by ATP-binding cassette transporters at the blood–brain barrier: implications for neuropsychopharmacology. Curr Pharm Des. 2011;17:2829–2842. doi: 10.2174/138161211797440203. PubMed DOI

Ueda K, Okamura N, Hirai M, Tanigawara Y, Saeki T, Kioka N, et al. Human P-glycoprotein transports cortisol, aldosterone, and dexamethasone, but not progesterone. J Biol Chem. 1992;267:24248–24252. PubMed

Zlokovic BV. The blood–brain barrier in health and chronic neurodegenerative disorders. Neuron. 2008;57:178–201. doi: 10.1016/j.neuron.2008.01.003. PubMed DOI

Johanson C, Stopa E, McMillan P, Roth D, Funk J, Krinke G. The distributional nexus of choroid plexus to cerebrospinal fluid, ependyma and brain: toxicologic/pathologic phenomena, periventricular destabilization, and lesion spread. Toxicol Pathol. 2011;39:186–212. doi: 10.1177/0192623310394214. PubMed DOI

Choudhuri S, Cherrington NJ, Li N, Klaassen CD. Constitutive expression of various xenobiotic and endobitic transporter mRNAs in the choroid plexus of rats. Drug Metab Dispos. 2003;31:1337–1345. doi: 10.1124/dmd.31.11.1337. PubMed DOI

Gao B, Meier PJ. Organic anion transport across the choroid plexus. Microsc Res Tech. 2001;52:60–64. doi: 10.1002/1097-0029(20010101)52:1<60::aid-jemt8>3.0.co;2-c. PubMed DOI

Hagenbuch B, Meier PJ. The superfamily of organic anion transporting polypeptides. Biochim Biophys Acta. 2003;1609:1–18. doi: 10.1016/s0005-2736(02)00633-8. PubMed DOI

Teuscher NS, Keep RF, Smith DE. PEPT2-mediated uptake of neuropeptides in rat choroid plexus. Pharm Res. 2001;18:807–813. doi: 10.1023/a:1011088413043. PubMed DOI

Zhang H, Song Y-N, Liu W-G, Guo X-L, Yu L-G. Regulation and role of organic anion-transporting polypeptides (OATPs) in drug delivery at the choroid plexus. J Clin Neurosci. 2010;17:679–684. doi: 10.1016/j.jocn.2009.11.001. PubMed DOI

Engelhardt B, Sorokin L. The blood–brain and the blood–cerebrospinal fluid barriers: function and dysfunction. Sem Immunopathol. 2009;31:497–511. doi: 10.1007/s00281-009-0177-0. PubMed DOI

Redzic Z. Molecular biology of the blood–brain and the blood–cerebrospinal fluid barriers: similarities and differences. Fluids Barriers CNS. 2011;8:3. doi: 10.1186/2045-8118-8-3. PubMed DOI PMC

Saito Y, Wright EM. Regulation of bicarbonate transport across the brush border membrane of the bull-frog choroid plexus. J Physiol. 1984;350:327–342. doi: 10.1113/jphysiol.1984.sp015204. PubMed DOI PMC

van Deurs B, Koehler JK. Tight junctions in the choroid plexus epithelium. A freeze-fracture study including complementary replicas. J Cell Biol. 1979;80:662–673. doi: 10.1083/jcb.80.3.662. PubMed DOI PMC

Wolburg H, Lippoldt A. Tight junctions of the blood–brain barrier: development, composition and regulation. Vasc Pharmacol. 2002;38:323–337. doi: 10.1016/s1537-1891(02)00200-8. PubMed DOI

Furuse M, Hirase T, Itoh M, Nagafuchi A, Yonemura S, Tsukita S, et al. Occludin: a novel integral membrane protein localizing at tight junctions. J Cell Biol. 1993;123:1777–1788. doi: 10.1083/jcb.123.6.1777. PubMed DOI PMC

Wolburg H, Wolburg-Buchholz K, Liebner S, Engelhardt B. Claudin-1, claudin-2 and claudin-11 are present in tight junctions of choroid plexus epithelium of the mouse. Neurosci Lett. 2001;307:77–80. doi: 10.1016/S0304-3940(01)01927-9. PubMed DOI

Wong V, Gumbiner BM. A synthetic peptide corresponding to the extracellular domain of occludin perturbs the tight junction permeability barrier. J Cell Biol. 1997;136:399–409. doi: 10.1083/jcb.136.2.399. PubMed DOI PMC

Kratzer I, Vasiljevic A, Rey C, Fevre-Montange M, Saunders N, Strazielle N, et al. Complexity and developmental changes in the expression pattern of claudins at the blood-CSF barrier. Histochem Cell Biol. 2012;138:861–879. doi: 10.1007/s00418-012-1001-9. PubMed DOI PMC

Lippoldt A, Liebner S, Andbjer B, Kalbacher H, Wolburg H, Haller H, et al. Organization of choroid plexus epithelial and endothelial cell tight junctions and regulation of claudin-1, -2 and -5 expression by protein kinase C. NeuroReport. 2000;11:1427–1431. doi: 10.1097/00001756-200005150-00015. PubMed DOI

Tsukita S, Furuse M, Itoh M. Multifunctional strands in tight junctions. Nat Rev Mol Cell Biol. 2001;2:285–293. doi: 10.1038/35067088. PubMed DOI

Tsukita S, Furuse M. Occludin and claudins in tight-junction strands: leading or supporting players? Trends Cell Biol. 1999;9:268–273. doi: 10.1016/s0962-8924(99)01578-0. PubMed DOI

Brightman MW, Reese TS. Junctions between intimately apposed cell membranes in the vertebrate brain. J Cell Biol. 1969;40:648–677. doi: 10.1083/jcb.40.3.648. PubMed DOI PMC

Vorbrodt AW, Dobrogowska DH. Molecular anatomy of intercellular junctions in brain endothelial and epithelial barriers: electron microscopist’s view. Brain Res Brain Res Rev. 2003;42:221–242. doi: 10.1016/s0165-0173(03)00177-2. PubMed DOI

Stevenson BR, Siliciano JD, Mooseker MS, Goodenough DA. Identification of ZO-1: a high molecular weight polypeptide associated with the tight junction (zonula occludens) in a variety of epithelia. J Cell Biol. 1986;103:755–766. doi: 10.1083/jcb.103.3.755. PubMed DOI PMC

Anderson JM, Stevenson BR, Jesaitis LA, Goodenough DA, Mooseker MS. Characterization of ZO-1, a protein component of the tight junction from mouse liver and Madin-Darby canine kidney cells. J Cell Biol. 1988;106:1141–1149. doi: 10.1083/jcb.106.4.1141. PubMed DOI PMC

Jesaitis LA, Goodenough DA. Molecular characterization and tissue distribution of ZO-2, a tight junction protein homologous to ZO-1 and the Drosophila discs-large tumor suppressor protein. J Cell Biol. 1994;124:949–961. doi: 10.1083/jcb.124.6.949. PubMed DOI PMC

Gumbiner B, Lowenkopf T, Apatira D. Identification of a 160-kDa polypeptide that binds to the tight junction protein ZO-1. PNAS. 1991;88:3460–3464. doi: 10.1073/pnas.88.8.3460. PubMed DOI PMC

Haskins J, Gu L, Wittchen ES, Hibbard J, Stevenson BR. ZO-3, a novel member of the MAGUK protein family found at the tight junction, interacts with ZO-1 and occludin. J Cell Biol. 1998;141:199–208. doi: 10.1083/jcb.141.1.199. PubMed DOI PMC

Balda MS, Gonzalez-Mariscal L, Matter K, Cereijido M, Anderson JM. Assembly of the tight junction: the role of diacylglycerol. J Cell Biol. 1993;123:293–302. doi: 10.1083/jcb.123.2.293. PubMed DOI PMC

González-Mariscal L, Betanzos A, Avila-Flores A. MAGUK proteins: structure and role in the tight junction. Semin Cell Dev Biol. 2000;11:315–324. doi: 10.1006/scdb.2000.0178. PubMed DOI

Itoh M, Furuse M, Morita K, Kubota K, Saitou M, Tsukita S. Direct binding of three tight junction-associated Maguks, Zo-1, Zo-2, and Zo-3, with the Cooh Termini of Claudins. J Cell Biol. 1999;147:1351–1363. doi: 10.1083/jcb.147.6.1351. PubMed DOI PMC

Harris BZ, Lim WA. Mechanism and role of PDZ domains in signaling complex assembly. J Cell Sci. 2001;114:3219–3231. PubMed

Gomperts SN. Clustering membrane proteins: it’s all coming together with the PSD-95/SAP90 protein family. Cell. 1996;84:659–662. doi: 10.1016/s0092-8674(00)81043-0. PubMed DOI

Tietz S, Engelhardt B. Brain barriers: crosstalk between complex tight junctions and adherens junctions. J Cell Biol. 2015;209:493–506. doi: 10.1083/jcb.201412147. PubMed DOI PMC

Lobas MA, Helsper L, Vernon CG, Schreiner D, Zhang Y, Holtzman MJ, et al. Molecular heterogeneity in the choroid plexus epithelium: the 22-member γ-protocadherin family is differentially expressed, apically localized, and implicated in CSF regulation. J Neurochem. 2012;120:913–927. doi: 10.1111/j.1471-4159.2011.07587.x. PubMed DOI PMC

Koval M. Pathways and control of connexin oligomerization. Trend Cell Biol. 2006;16:159–166. doi: 10.1016/j.tcb.2006.01.006. PubMed DOI PMC

Song H, Zheng G, Liu Y, Shen X-F, Zhao Z-H, Aschner M, et al. Cellular uptake of lead in the blood–cerebrospinal fluid barrier: novel roles of Connexin 43 hemichannel and its down-regulations via Erk phosphorylation. Toxicol Appl Pharmacol. 2016;297:1–11. doi: 10.1016/j.taap.2016.02.021. PubMed DOI

Dermietzel R, Spray DC. Gap junctions in the brain: where, what type, how many and why? Trends Neurosci. 1993;16:186–192. doi: 10.1016/0166-2236(93)90151-b. PubMed DOI

Jovanova-Nesic K, Koruga D, Kojic D, Kostic V, Rakic L, Shoenfeld Y. Choroid plexus connexin 43 expression and gap junction flexibility are associated with clinical features of acute EAE. Ann N Y Acad Sci. 2009;1173:75–82. doi: 10.1111/j.1749-6632.2009.04658.x. PubMed DOI

Marques F, Sousa JC, Coppola G, Falcao AM, Rodrigues AJ, Geschwind DH, et al. Kinetic profile of the transcriptome changes induced in the choroid plexus by peripheral inflammation. J Cereb Blood Flow Metab. 2009;29:921–932. doi: 10.1038/jcbfm.2009.15. PubMed DOI

Marques F, Sousa JC, Correia-Neves M, Oliveira P, Sousa N, Palha JA. The choroid plexus response to peripheral inflammatory stimulus. Neuroscience. 2007;144:424–430. doi: 10.1016/j.neuroscience.2006.09.029. PubMed DOI

Ip JPK, Noçon AL, Hofer MJ, Lim SL, Müller M, Campbell IL. Lipocalin 2 in the central nervous system host response to systemic lipopolysaccharide administration. J Neuroinflammation. 2011;8:124. doi: 10.1186/1742-2094-8-124. PubMed DOI PMC

Marques F, Rodrigues A-J, Sousa JC, Coppola G, Geschwind DH, Sousa N, et al. Lipocalin 2 is a choroid plexus acute-phase protein. J Cereb Blood Flow Metab. 2008;28:450–455. doi: 10.1038/sj.jcbfm.9600557. PubMed DOI

Flo TH, Smith KD, Sato S, Rodriguez DJ, Holmes MA, Strong RK, et al. Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Nature. 2004;432:917–921. doi: 10.1038/nature03104. PubMed DOI

Goetz DH, Holmes MA, Borregaard N, Bluhm ME, Raymond KN, Strong RK. The neutrophil lipocalin NGAL Is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition. Mol Cell. 2002;10:1033–1043. doi: 10.1016/S1097-2765(02)00708-6. PubMed DOI

Marques F, Falcao AM, Sousa JC, Coppola G, Geschwind D, Sousa N, et al. Altered iron metabolism is part of the choroid plexus response to peripheral inflammation. Endocrinology. 2009;150:2822–2828. doi: 10.1210/en.2008-1610. PubMed DOI

Verstrepen L, Bekaert T, Chau T-L, Tavernier J, Chariot A, Beyaert R. TLR-4, IL-1R and TNF-R signaling to NF-kappaB: variations on a common theme. Cell Mol Life Sci. 2008;65:2964–2978. doi: 10.1007/s00018-008-8064-8. PubMed DOI PMC

Wright SD. Toll, a new piece in the puzzle of innate immunity. J Exp Med. 1999;189:605–609. doi: 10.1084/jem.189.4.605. PubMed DOI PMC

Chakravarty S, Herkenham M. Toll-like receptor 4 on nonhematopoietic cells sustains CNS inflammation during endotoxemia, independent of systemic cytokines. J Neurosci. 2005;25:1788–1796. doi: 10.1523/JNEUROSCI.4268-04.2005. PubMed DOI PMC

Kowalewska M, Szczepkowska A, Herman AP, Pellicer-Rubio MT, Jałyński M, Skipor J. Melatonin from slow-release implants did not influence the gene expression of the lipopolysaccharide receptor complex in the choroid plexus of seasonally anoestrous adult ewes subjected or not to a systemic inflammatory stimulus. Small Ruminant Res. 2017;147:1–7. doi: 10.1016/j.smallrumres.2016.11.018. DOI

Lacroix S, Feinstein D, Rivest S. The bacterial endotoxin lipopolysaccharide has the ability to target the brain in upregulating its membrane CD14 receptor within specific cellular populations. Brain Pathol. 1998;8:625–640. doi: 10.1111/j.1750-3639.1998.tb00189.x. PubMed DOI PMC

Lacroix S, Rivest S. Effect of acute systemic inflammatory response and cytokines on the transcription of the genes encoding cyclooxygenase enzymes (COX-1 and COX-2) in the rat brain. J Neurochem. 1998;70:452–466. doi: 10.1046/j.1471-4159.1998.70020452.x. PubMed DOI

Laflamme N, Rivest S. Toll-like receptor 4: the missing link of the cerebral innate immune response triggered by circulating gram-negative bacterial cell wall components. FASEB J. 2001;15:155–163. doi: 10.1096/fj.00-0339com. PubMed DOI

Quan N, Whiteside M, Kim L, Herkenham M. Induction of inhibitory factor κBα mRNA in the central nervous system after peripheral lipopolysaccharide administration: an in situ hybridization histochemistry study in the rat. PNAS. 1997;94:10985–10990. doi: 10.1073/pnas.94.20.10985. PubMed DOI PMC

Stridh L, Ek CJ, Wang X, Nilsson H, Mallard C. Regulation of toll-like receptors in the choroid plexus in the immature brain after systemic inflammatory stimuli. Transl Stroke Res. 2013;4:220–227. doi: 10.1007/s12975-012-0248-8. PubMed DOI PMC

Chiu P-S, Lai S-C. Matrix metalloproteinase-9 leads to claudin-5 degradation via the NF-κB pathway in BALB/c mice with eosinophilic meningoencephalitis caused by Angiostrongylus cantonensis. PLoS ONE. 2013;8:e53370. doi: 10.1371/journal.pone.0053370. PubMed DOI PMC

Vandenbroucke RE, Dejonckheere E, Lint PV, Demeestere D, Wonterghem EV, Vanlaere I, et al. Matrix metalloprotease 8-dependent extracellular matrix cleavage at the blood–CSF barrier contributes to lethality during systemic inflammatory diseases. J Neurosci. 2012;32:9805–9816. doi: 10.1523/JNEUROSCI.0967-12.2012. PubMed DOI PMC

Nadeau S, Rivest S. Regulation of the gene encoding tumor necrosis factor alpha (TNF-alpha) in the rat brain and pituitary in response in different models of systemic immune challenge. J Neuropathol Exp Neurol. 1999;58:61–77. doi: 10.1097/00005072-199901000-00008. PubMed DOI

Schwerk C, Rybarczyk K, Essmann F, Seibt A, Mölleken M-L, Zeni P, et al. TNF induces choroid plexus epithelial cell barrier alterations by apoptotic and nonapoptotic mechanisms. Biomed Res Int. 2010 doi: 10.1155/2010/307231. PubMed DOI PMC

Kowalewska M, Herman AP, Szczepkowska A, Skipor J. The effect of melatonin from slow-release implants on basic and TLR-4-mediated gene expression of inflammatory cytokines and their receptors in the choroid plexus in ewes. Res Vet Sci. 2017;113:50–55. doi: 10.1016/j.rvsc.2017.09.003. PubMed DOI

Thibeault I, Laflamme N, Rivest S. Regulation of the gene encoding the monocyte chemoattractant protein 1 (MCP-1) in the mouse and rat brain in response to circulating LPS and proinflammatory cytokines. J Comp Neurol. 2001;434:461–477. doi: 10.1002/cne.1187. PubMed DOI

Marques F, Sousa JC, Coppola G, Geschwind DH, Sousa N, Palha JA, et al. The choroid plexus response to a repeated peripheral inflammatory stimulus. BMC Neurosci. 2009;10:135. doi: 10.1186/1471-2202-10-135. PubMed DOI PMC

Melo GD, Machado GF. Choroid plexus involvement in dogs with spontaneous visceral leishmaniasis: a histopathological investigation. Braz J Vet Pathol. 2009;2:69–74.

Balusu S, Van Wonterghem E, De Rycke R, Raemdonck K, Stremersch S, Gevaert K, et al. Identification of a novel mechanism of blood–brain communication during peripheral inflammation via choroid plexus-derived extracellular vesicles. EMBO Mol Med. 2016;8:1162–1183. doi: 10.15252/emmm.201606271. PubMed DOI PMC

Dando SJ, Mackay-Sim A, Norton R, Currie BJ, St. John JA, Ekberg JAK, et al. Pathogens penetrating the central nervous system: infection pathways and the cellular and molecular mechanisms of invasion. Clin Microbiol Rev. 2014;27:691–726. doi: 10.1128/cmr.00118-13. PubMed DOI PMC

Meeker RB, Williams K, Killebrew DA, Hudson LC. Cell trafficking through the choroid plexus. Cell Adh Migr. 2012;6:390–396. doi: 10.4161/cam.21054. PubMed DOI PMC

Tenenbaum T, Matalon D, Adam R, Seibt A, Wewer C, Schwerk C, et al. Dexamethasone prevents alteration of tight junction-associated proteins and barrier function in porcine choroid plexus epithelial cells after infection with Streptococcus suis in vitro. Brain Res. 2008;1229:1–17. doi: 10.1016/j.brainres.2008.06.118. PubMed DOI

Adam RA, Tenenbaum T, Valentin-Weigand P, Laryea M, Schwahn B, Angelow S, et al. Porcine choroid plexus epithelial cells induce Streptococcus suis bacteriostasis in vitro. Infect Immun. 2004;72:3084–3087. doi: 10.1128/iai.72.5.3084-3087.2004. PubMed DOI PMC

de Greeff A, Benga L, Wichgers Schreur PJ, Valentin-Weigand P, Rebel JMJ, Smith HE. Involvement of NF-kappaB and MAP-kinases in the transcriptional response of alveolar macrophages to Streptococcus suis. Vet Microbiol. 2010;141:59–67. doi: 10.1016/j.vetmic.2009.07.031. PubMed DOI

Schwerk C, Adam R, Borkowski J, Schneider H, Klenk M, Zink S, et al. In vitro transcriptome analysis of porcine choroid plexus epithelial cells in response to Streptococcus suis: release of pro-inflammatory cytokines and chemokines. Microbes Infect. 2011;13:953–962. doi: 10.1016/j.micinf.2011.05.012. PubMed DOI

Tenenbaum T, Essmann F, Adam R, Seibt A, Jänicke RU, Novotny GEK, et al. Cell death, caspase activation, and HMGB1 release of porcine choroid plexus epithelial cells during Streptococcus suis infection in vitro. Brain Res. 2006;1100:1–12. doi: 10.1016/j.brainres.2006.05.041. PubMed DOI

Tenenbaum T, Papandreou T, Gellrich D, Friedrichs U, Seibt A, Adam R, et al. Polar bacterial invasion and translocation of Streptococcus suis across the blood–cerebrospinal fluid barrier in vitro. Cell Microbiol. 2009;11:323–336. doi: 10.1111/j.1462-5822.2008.01255.x. PubMed DOI

Williams AE, Blakemore WF. Pathogenesis of meningitis caused by Streptococcus suis type 2. J Infect Dis. 1990;162:474–481. doi: 10.1093/infdis/162.2.474. PubMed DOI

Wewer C, Seibt A, Wolburg H, Greune L, Schmidt MA, Berger J, et al. Transcellular migration of neutrophil granulocytes through the blood–cerebrospinal fluid barrier after infection with Streptococcus suis. J Neuroinflammation. 2011;8:51. doi: 10.1186/1742-2094-8-51. PubMed DOI PMC

Iovino F, Orihuela CJ, Moorlag HE, Molema G, Bijlsma JJE. Interactions between blood-borne Streptococcus pneumoniae and the blood–brain barrier preceding meningitis. PLoS ONE. 2013;8:e68408. doi: 10.1371/journal.pone.0068408. PubMed DOI PMC

Echchannaoui H, Bachmann P, Letiembre M, Espinosa M, Landmann R. Regulation of Streptococcus pneumoniae distribution by Toll-like receptor 2 in vivo. Immunobiology. 2005;210:229–236. doi: 10.1016/j.imbio.2005.05.017. PubMed DOI

Bitsch A, Trostdorf F, Brück W, Schmidt H, Fischer FR, Nau R. Central nervous system TNFα-mRNA expression during rabbit experimental pneumococcal meningitis. Neurosci Lett. 1997;237:105–108. doi: 10.1016/S0304-3940(97)00830-6. PubMed DOI

Berche P. Bacteremia is required for invasion of the murine central nervous system by Listeria monocytogenes. Microb Pathog. 1995;18:323–336. doi: 10.1006/mpat.1995.0029. PubMed DOI

Bonazzi M, Lecuit M, Cossart P. Listeria monocytogenes internalin and E-cadherin: from structure to pathogenesis. Cell Microbiol. 2009;11:693–702. doi: 10.1111/j.1462-5822.2009.01293.x. PubMed DOI

Gründler T, Quednau N, Stump C, Orian-Rousseau V, Ishikawa H, Wolburg H, et al. The surface proteins InlA and InlB are interdependently required for polar basolateral invasion by Listeria monocytogenes in a human model of the blood–cerebrospinal fluid barrier. Microbes Infect. 2013;15:291–301. doi: 10.1016/j.micinf.2012.12.005. PubMed DOI

Dinner S, Kaltschmidt J, Stump-Guthier C, Hetjens S, Ishikawa H, Tenenbaum T, et al. Mitogen-activated protein kinases are required for effective infection of human choroid plexus epithelial cells by Listeria monocytogenes. Microbes Infect. 2017;19:18–33. doi: 10.1016/j.micinf.2016.09.003. PubMed DOI

Parkkinen J, Korhonen TK, Pere A, Hacker J, Soinila S. Binding sites in the rat brain for Escherichia coli S fimbriae associated with neonatal meningitis. J Clin Invest. 1988;81:860–865. doi: 10.1172/JCI113395. PubMed DOI PMC

Rose R, Häuser S, Stump-Guthier C, Weiss C, Rohde M, Kim KS, et al. Virulence factor-dependent basolateral invasion of choroid plexus epithelial cells by pathogenic Escherichia coli in vitro. FEMS Microbiol Lett. 2018;365:fny274. doi: 10.1093/femsle/fny274. PubMed DOI PMC

Sterk LMT, Van Alphen L, Geelen-Van Den Broek L, Houthoff HJ, Dankert J. Differential binding of Haemophilus influenzae to human tissues by fimbriae. J Med Microbiol. 1991;35:129–138. doi: 10.1099/00222615-35-3-129. PubMed DOI

Häuser S, Wegele C, Stump-Guthier C, Borkowski J, Weiss C, Rohde M, et al. Capsule and fimbriae modulate the invasion of Haemophilus influenzae in a human blood–cerebrospinal fluid barrier model. Int J Med Microbiol. 2018;308:829–839. doi: 10.1016/j.ijmm.2018.07.004. PubMed DOI

Schwerk C, Tenenbaum T, Kim KS, Schroten H. The choroid plexus—a multi-role player during infectious diseases of the CNS. Front Cell Neurosci. 2015 doi: 10.3389/fncel.2015.00080. PubMed DOI PMC

Schwerk C, Papandreou T, Schuhmann D, Nickol L, Borkowski J, Steinmann U, et al. Polar invasion and translocation of Neisseria meningitidis and Streptococcus suis in a novel human model of the blood–cerebrospinal fluid barrier. Borrow R, editor. PLoS ONE. 2012;7:e30069. doi: 10.1371/journal.pone.0030069. PubMed DOI PMC

Pron B, Taha M-K, Rambaud C, Fournet J-C, Pattey N, Monnet J-P, et al. Interaction of neisseria meningitidis with the components of the blood–brain barrier correlates with an increased expression of PilC. J Infect Dis. 1997;176:1285–1292. doi: 10.1086/514124. PubMed DOI

Borkowski J, Li L, Steinmann U, Quednau N, Stump-Guthier C, Weiss C, et al. Neisseria meningitidiselicits a pro-inflammatory response involving IκBζ in a human blood–cerebrospinal fluid barrier model. J Neuroinflammation. 2014;11:163. doi: 10.1186/s12974-014-0163-x. PubMed DOI PMC

Giorgi Rossi P, Mantovani J, Ferroni E, Forcina A, Stanghellini E, Curtale F, et al. Incidence of bacterial meningitis (2001–2005) in Lazio, Italy: the results of a integrated surveillance system. BMC Infect Dis. 2009;9:13. doi: 10.1186/1471-2334-9-13. PubMed DOI PMC

Kim J, Hetman M, Hattab EM, Joiner J, Alejandro B, Schroten H, et al. Zika virus infects pericytes in the choroid plexus and enters the central nervous system through the blood–cerebrospinal fluid barrier. bioRxiv. 2019 doi: 10.1101/841437. PubMed DOI PMC

Corbridge SM, Rice RC, Bean LA, Wüthrich C, Dang X, Nicholson DA, et al. JC virus infection of meningeal and choroid plexus cells in patients with progressive multifocal leukoencephalopathy. J Neurovirol. 2019;25:520–524. doi: 10.1007/s13365-019-00753-y. PubMed DOI PMC

Kramer-Hämmerle S, Rothenaigner I, Wolff H, Bell JE, Brack-Werner R. Cells of the central nervous system as targets and reservoirs of the human immunodeficiency virus. Virus Res. 2005;111:194–213. doi: 10.1016/j.virusres.2005.04.009. PubMed DOI

Dunfee R, Thomas ER, Gorry PR, Wang J, Ancuta P, Gabuzda D. Mechanisms of HIV-1 neurotropism. Curr HIV Res. 2006;4:267–278. doi: 10.2174/157016206777709500. PubMed DOI

Petito CK, Chen H, Mastri AR, Torres-Munoz J, Roberts B, Wood C. HIV infection of choroid plexus in AIDS and asymptomatic HIV-infected patients suggests that the choroid plexus may be a reservoir of productive infection. J Neurovirol. 1999;5:670–677. doi: 10.3109/13550289909021295. PubMed DOI

Chen H, Wood C, Petito CK. Comparisons of HIV-1 viral sequences in brain, choroid plexus and spleen: potential role of choroid plexus in the pathogenesis of HIV encephalitis. J Neurovirol. 2000;6:498–506. doi: 10.3109/13550280009091950. PubMed DOI

Falangola MF, Hanly A, Galvao-Castro B, Petito CK. HIV infection of human choroid plexus: a possible mechanism of viral entry into the CNS. J Neuropathol Exp Neurol. 1995;54:497–503. doi: 10.1097/00005072-199507000-00003. PubMed DOI

Bagasra O, Lavi E, Bobroski L, Khalili K, Pestaner JP, Tawadros R, et al. Cellular reservoirs of HIV-1 in the central nervous system of infected individuals: identification by the combination of in situ polymerase chain reaction and immunohistochemistry. AIDS. 1996;10:573–585. doi: 10.1097/00002030-199606000-00002. PubMed DOI

Hanly A, Petito CK. HLA-DR-positive dendritic cells of the normal human choroid plexus: a potential reservoir of HIV in the central nervous system. Hum Pathol. 1998;29:88–93. doi: 10.1016/s0046-8177(98)90395-1. PubMed DOI

Schneider H, Weber CE, Schoeller J, Steinmann U, Borkowski J, Ishikawa H, et al. Chemotaxis of T-cells after infection of human choroid plexus papilloma cells with Echovirus 30 in an in vitro model of the blood–cerebrospinal fluid barrier. Virus Res. 2012;170:66–74. doi: 10.1016/j.virusres.2012.08.019. PubMed DOI

Dahm T, Frank F, Adams O, Lindner HA, Ishikawa H, Weiss C, et al. Sequential transmigration of polymorphonuclear cells and naive CD3+ T lymphocytes across the blood–cerebrospinal–fluid barrier in vitro following infection with Echovirus 30. Virus Res. 2017;232:54–62. doi: 10.1016/j.virusres.2017.01.024. PubMed DOI

Tabor-Godwin JM, Ruller CM, Bagalso N, An N, Pagarigan RR, Harkins S, et al. A novel population of myeloid cells responding to coxsackievirus infection assists in the dissemination of virus within the neonatal CNS. J Neurosci. 2010;30:8676–8691. doi: 10.1523/JNEUROSCI.1860-10.2010. PubMed DOI PMC

WHO Director-General’s opening remarks at the media briefing on COVID-19—11 March 2020. https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19-11-march-2020.

Mao L, Wang M, Chen S, He Q, Chang J, Hong C, et al. Neurological manifestations of hospitalized patients with COVID-19 in Wuhan, China: a retrospective case series study. JAMA Neurol. 2020 doi: 10.1101/2020.02.22.20026500. PubMed DOI PMC

Desforges M, Le Coupanec A, Dubeau P, Bourgouin A, Lajoie L, Dubé M, et al. Human coronaviruses and other respiratory viruses: underestimated opportunistic pathogens of the central nervous system? Viruses. 2019 doi: 10.3390/v12010014. PubMed DOI PMC

Chang YC, Stins MF, McCaffery MJ, Miller GF, Pare DR, Dam T, et al. Cryptococcal yeast cells invade the central nervous system via transcellular penetration of the blood–brain barrier. Infect Immun. 2004;72:4985–4995. doi: 10.1128/IAI.72.9.4985-4995.2004. PubMed DOI PMC

Charlier C, Chrétien F, Baudrimont M, Mordelet E, Lortholary O, Dromer F. Capsule structure changes associated with Cryptococcus neoformans crossing of the blood–brain barrier. Am J Pathol. 2005;166:421–432. doi: 10.1016/S0002-9440(10)62265-1. PubMed DOI PMC

Liu T-B, Perlin D, Xue C. Molecular mechanisms of cryptococcal meningitis. Virulence. 2012;3:173–181. doi: 10.4161/viru.18685. PubMed DOI PMC

Hammoud DA, Mahdi E, Panackal AA, Wakim P, Sheikh V, Sereti I, et al. Choroid plexitis and ependymitis by magnetic resonance imaging are biomarkers of neuronal damage and inflammation in HIV-negative cryptococcal meningoencephalitis. Sci Rep. 2017;7:1–8. doi: 10.1038/s41598-017-09694-0. PubMed DOI PMC

Kumari R, Raval M, Dhun A. Cryptococcal choroid plexitis: rare imaging findings of central nervous system cryptococcal infection in an immunocompetent individual. Br J Radiol. 2010;83:e014–e017. doi: 10.1259/bjr/50945216. PubMed DOI PMC

Kovoor JME, Mahadevan A, Narayan JP, Govindappa SS, Satishchandra P, Taly AV, et al. Cryptococcal choroid plexitis as a mass lesion: mR imaging and histopathologic correlation. AJNR Am J Neuroradiol. 2002;23:273–276. PubMed PMC

Masocha W, Kristensson K. Passage of parasites across the blood–brain barrier. Virulence. 2012;3:202–212. doi: 10.4161/viru.19178. PubMed DOI PMC

Abolarin MO, Evans DA, Tovey DG, Ormerod WE. Cryptic stage of sleeping-sickness trypanosome developing in choroid plexus epithelial cells. Br Med J (Clin Res Ed) 1982;285:1380–1382. doi: 10.1136/bmj.285.6352.1380. PubMed DOI PMC

Biswas D, Choudhury A, Misra KK. Histopathology of Trypanosoma (Trypanozoon) evansi infection in Bandicoot rat. II. Brain and choroid plexus. Proc Zool Soc. 2010;63:27–37. doi: 10.1007/s12595-010-0004-6. DOI

Melo GD, Silva JES, Grano FG, Souza MS, Machado GF. Leishmania infection and neuroinflammation: specific chemokine profile and absence of parasites in the brain of naturally-infected dogs. J Neuroimmunol. 2015;289:21–29. doi: 10.1016/j.jneuroim.2015.10.004. PubMed DOI

Melo GD, Silva JES, Grano FG, Homem CG, Machado GF. Compartmentalized gene expression of toll-like receptors 2, 4 and 9 in the brain and peripheral lymphoid organs during canine visceral leishmaniasis. Parasite Immunol. 2014;36:726–731. doi: 10.1111/pim.12148. PubMed DOI

Chaudhry SR, Hafez A, Rezai Jahromi B, Kinfe TM, Lamprecht A, Niemelä M, et al. Role of damage associated molecular pattern molecules (DAMPs) in aneurysmal subarachnoid hemorrhage (aSAH) Int J Mol Sci. 2018;19:2035. doi: 10.3390/ijms19072035. PubMed DOI PMC

Okada T, Suzuki H. Toll-like receptor 4 as a possible therapeutic target for delayed brain injuries after aneurysmal subarachnoid hemorrhage. Neural Regen Res. 2017;12:193–196. doi: 10.4103/1673-5374.200795. PubMed DOI PMC

Kwon MS, Woo SK, Kurland DB, Yoon SH, Palmer AF, Banerjee U, et al. Methemoglobin is an endogenous toll-like receptor 4 ligand-relevance to subarachnoid hemorrhage. Int J Mol Sci. 2015;16:5028–5046. doi: 10.3390/ijms16035028. PubMed DOI PMC

Rivest S. Regulation of innate immune responses in the brain. Nat Rev Immunol. 2009;9:429–439. doi: 10.1038/nri2565. PubMed DOI

Karimy JK, Zhang J, Kurland DB, Theriault BC, Duran D, Stokum JA, et al. Inflammation-dependent cerebrospinal fluid hypersecretion by the choroid plexus epithelium in posthemorrhagic hydrocephalus. Nat Med. 2017;23:997–1003. doi: 10.1038/nm.4361. PubMed DOI

Gram M, Sveinsdottir S, Cinthio M, Sveinsdottir K, Hansson SR, Mörgelin M, et al. Extracellular hemoglobin—mediator of inflammation and cell death in the choroid plexus following preterm intraventricular hemorrhage. J Neuroinflammation. 2014;11:200. doi: 10.1186/s12974-014-0200-9. PubMed DOI PMC

Liszczak TM, Black PM, Tzouras A, Foley L, Zervas NT. Morphological changes of the basilar artery, ventricles, and choroid plexus after experimental SAH. J Neurosurg. 1984;61:486–493. doi: 10.3171/jns.1984.61.3.0486. PubMed DOI

Solár P, Klusáková I, Jančálek R, Dubový P, Joukal M. Subarachnoid hemorrhage induces dynamic immune cell reactions in the choroid plexus. Front Cell Neurosci. 2020 doi: 10.3389/fncel.2020.00018. PubMed DOI PMC

Wan Y, Hua Y, Garton HJL, Novakovic N, Keep RF, Xi G. Activation of epiplexus macrophages in hydrocephalus caused by subarachnoid hemorrhage and thrombin. CNS Neurosci Ther. 2019;25:1134–1141. doi: 10.1111/cns.13203. PubMed DOI PMC

Karimy JK, Zhang J, Kurland DB, Theriault BC, Duran D, Furey CG, et al. 166 TLR-4-regulated cerebrospinal fluid hypersecretion in post-hemorrhagic hydrocephalus. Neurosurgery. 2017;64:242. doi: 10.1093/neuros/nyx417.166. DOI

Zeni P, Doepker E, Topphoff US, Huewel S, Tenenbaum T, Galla H-J. MMPs contribute to TNF-α-induced alteration of the blood–cerebrospinal fluid barrier in vitro. Am J Physiol-Cell Physiol. 2007;293:C855–C864. doi: 10.1152/ajpcell.00470.2006. PubMed DOI

Demirgil BT, Tugcu B, Postalci L, Guclu G, Dalgic A, Oral Z. Factors leading to hydrocephalus after aneurysmal subarachnoid hemorrhage. Minim Invasive Neurosurg. 2003;46:344–348. doi: 10.1055/s-2003-812500. PubMed DOI

Kim J, Jung Y. Increased aquaporin-1 and Na+-K+-2Cl– cotransporter 1 expression in choroid plexus leads to blood–cerebrospinal fluid barrier disruption and necrosis of hippocampal CA1 cells in acute rat models of hyponatremia. J Neurosci Res. 2012;90:1437–1444. doi: 10.1002/jnr.23017. PubMed DOI

Aydin MD, Kanat A, Turkmenoglu ON, Yolas C, Gundogdu C, Aydın N. Changes in number of water-filled vesicles of choroid plexus in early and late phase of experimental rabbit subarachnoid hemorrhage model: the role of petrous ganglion of glossopharyngeal nerve. Acta Neurochir. 2014;156:1311–1317. doi: 10.1007/s00701-014-2088-7. PubMed DOI

Kanat A, Turkmenoglu O, Aydin MD, Yolas C, Aydin N, Gursan N, et al. Toward changing of the pathophysiologic basis of acute hydrocephalus after subarachnoid hemorrhage: a preliminary experimental study. World Neurosurg. 2013;80:390–395. doi: 10.1016/j.wneu.2012.12.020. PubMed DOI

Niemelä M, Marbacher S. Acute hydrocephalus after subarachnoid hemorrhage–can it be caused by water vesicles of choroid plexuses? World Neurosurg. 2013;80:307–308. doi: 10.1016/j.wneu.2013.02.021. PubMed DOI

Long C-Y, Huang G-Q, Du Q, Zhou L-Q, Zhou J-H. The dynamic expression of aquaporins 1 and 4 in rats with hydrocephalus induced by subarachnoid haemorrhage. Folia Neuropathol. 2019;57:182–195. doi: 10.5114/fn.2019.86296. PubMed DOI

Shibahara S, Kitamuro T, Takahashi K. Heme degradation and human disease: diversity is the soul of life. Antioxid Redox Sign. 2002;4:593–602. doi: 10.1089/15230860260220094. PubMed DOI

Schallner N, Pandit R, LeBlanc R, Thomas AJ, Ogilvy CS, Zuckerbraun BS, et al. Microglia regulate blood clearance in subarachnoid hemorrhage by heme oxygenase-1. J Clin Invest. 2015;125:2609–2625. doi: 10.1172/JCI78443. PubMed DOI PMC

Ewing JF, Weber CM, Maines MD. Biliverdin reductase is heat resistant and coexpressed with constitutive and heat shock forms of heme oxygenase in brain. J Neurochem. 1993;61:1015–1023. doi: 10.1111/j.1471-4159.1993.tb03615.x. PubMed DOI

Yilmaz A, Aydin MD, Kanat A, Musluman AM, Altas S, Aydin Y, et al. The effect of choroidal artery vasospasm on choroid plexus injury in subarachnoid hemorrhage: experimental study. Turk Neurosurg. 2011;21:477–482. doi: 10.5137/1019-5149.JTN.4204-11.1. PubMed DOI

Kotan D, Aydin MD, Gundogdu C, Aygul R, Aydin N, Ulvi H. Parallel development of choroid plexus degeneration and meningeal inflammation in subarachnoid hemorrhage—experimental study. Adv Clin Exp Med. 2014;23:699–704. doi: 10.17219/acem/37221. PubMed DOI

Yolas C, Ozdemir NG, Kanat A, Aydin MD, Keles P, Kepoglu U, et al. Uncovering a new cause of obstructive hydrocephalus following subarachnoid hemorrhage: choroidal artery vasospasm-related ependymal cell degeneration and aqueductal stenosis-first experimental study. World Neurosurg. 2016;90:484–491. doi: 10.1016/j.wneu.2016.03.049. PubMed DOI

Gillardon F, Lenz C, Kuschinsky W, Zimmermann M. Evidence for apoptotic cell death in the choroid plexus following focal cerebral ischemia. Neurosci Lett. 1996;207:113–116. doi: 10.1016/0304-3940(96)12508-8. PubMed DOI

Traystman RJ. Animal models of focal and global cerebral ischemia. ILAR J. 2003;44:85–95. doi: 10.1093/ilar.44.2.85. PubMed DOI

Hupperts RM, Lodder J, Heuts-van Raak EP, Kessels F. Infarcts in the anterior choroidal artery territory: anatomical distribution, clinical syndromes, presumed pathogenesis and early outcome. Brain. 1994;117:825–834. doi: 10.1093/brain/117.4.825. PubMed DOI

Pulsinelli WA, Brierley JB, Plum F. Temporal profile of neuronal damage in a model of transient forebrain ischemia. Ann Neurol. 1982;11:491–498. doi: 10.1002/ana.410110509. PubMed DOI

Ennis SR, Keep RF. Forebrain ischemia and the blood–cerebrospinal fluid barrier. In: Hoff JT, Keep RF, Xi G, Hua Y, editors. Brain Edema XIII, Acta Neurochir Supplementum. Vienna: Springer; 2006. pp. 276–278. PubMed

Johanson CE, Palm DE, Primiano MJ, McMillan PN, Chan P, Knuckey NW, et al. Choroid plexus recovery after transient forebrain ischemia: role of growth factors and other repair mechanisms. Cell Mol Neurobiol. 2000;20:197–216. doi: 10.1023/A:1007097622590. PubMed DOI

Nagahiro S, Goto S, Korematsu K, Sumi M, Takahashi M, Ushio Y. Disruption of the blood–cerebrospinal fluid barrier by transient cerebral ischemia. Brain Res. 1994;633:305–311. doi: 10.1016/0006-8993(94)91553-9. PubMed DOI

Palm D, Knuckey N, Guglielmo M, Watson P, Primiano M, Johanson C. Choroid plexus electrolytes and ultrastructure following transient forebrain ischemia. Am J Physiol. 1995;269:R73–R79. doi: 10.1152/ajpregu.1995.269.1.R73. PubMed DOI

Akdemir G, Kaymaz F, Gursoy-Özdemir Y, Akalan N, Akdemir ES. The time course changes in expression of aquaporin 4 and aquaporin 1 following global cerebral ischemic edema in rat. Surg Neurol Int. 2016;7:4. doi: 10.4103/2152-7806.173316. PubMed DOI PMC

Ikeda J, Mies G, Nowak TS, Joó F, Klatzo I. Evidence for increased calcium influx across the choroid plexus following brief ischemia of gerbil brain. Neurosci Lett. 1992;142:257–259. doi: 10.1016/0304-3940(92)90386-L. PubMed DOI

Béjot Y, Prigent-Tessier A, Cachia C, Giroud M, Mossiat C, Bertrand N, et al. Time-dependent contribution of non neuronal cells to BDNF production after ischemic stroke in rats. Neurochem Int. 2011;58:102–111. doi: 10.1016/j.neuint.2010.10.019. PubMed DOI

Ennis SR, Keep RF. The effects of cerebral ischemia on the rat choroid plexus. J Cereb Blood Flow Metab. 2006;26:675–683. doi: 10.1038/sj.jcbfm.9600224. PubMed DOI

Kozniewska E, Romaniuk K. Vasopressin in vascular regulation and water homeostasis in the brain. J Physiol Pharmacol. 2008;59(Suppl 8):109–116. PubMed

Batra A, Latour LL, Ruetzler CA, Hallenbeck JM, Spatz M, Warach S, et al. Increased plasma and tissue MMP levels are associated with BCSFB and BBB disruption evident on post-contrast FLAIR after experimental stroke. J Cereb Blood Flow Metab. 2010;30:1188–1199. doi: 10.1038/jcbfm.2010.1. PubMed DOI PMC

Li Y, Chen J, Chopp M. Cell proliferation and differentiation from ependymal, subependymal and choroid plexus cells in response to stroke in rats. J Neurol Sci. 2002;193:137–146. doi: 10.1016/s0022-510x(01)00657-8. PubMed DOI

Knuckey NW, Finch P, Palm DE, Primiano MJ, Johanson CE, Flanders KC, et al. Differential neuronal and astrocytic expression of transforming growth factor beta isoforms in rat hippocampus following transient forebrain ischemia. Mol Brain Res. 1996;40:1–14. doi: 10.1016/0169-328X(96)00016-2. PubMed DOI

Sivakumar V, Lu J, Ling EA, Kaur C. Vascular endothelial growth factor and nitric oxide production in response to hypoxia in the choroid plexus in neonatal brain. Brain Pathol. 2008;18:71–85. doi: 10.1111/j.1750-3639.2007.00104.x. PubMed DOI PMC

Yao X, Miao W, Li M, Wang M, Ma J, Wang Y, et al. Protective effect of albumin on VEGF and brain edema in acute ischemia in rats. Neurosci Lett. 2010;472:179–183. doi: 10.1016/j.neulet.2010.02.002. PubMed DOI

Llovera G, Benakis C, Enzmann G, Cai R, Arzberger T, Ghasemigharagoz A, et al. The choroid plexus is a key cerebral invasion route for T cells after stroke. Acta Neuropathol. 2017;134:851–868. doi: 10.1007/s00401-017-1758-y. PubMed DOI

Ge R, Tornero D, Hirota M, Monni E, Laterza C, Lindvall O, et al. Choroid plexus-cerebrospinal fluid route for monocyte-derived macrophages after stroke. J Neuroinflammation. 2017;14:153. doi: 10.1186/s12974-017-0909-3. PubMed DOI PMC

Ferrand-Drake M. Cell death in the choroid plexus following transient forebrain global ischemia in the rat. Microsc Res Tech. 2001;52:130–136. doi: 10.1002/1097-0029(20010101)52:1<130::AID-JEMT14>3.0.CO;2-6. PubMed DOI

Borlongan CV, Skinner SJM, Geaney M, Vasconcellos AV, Elliott RB, Emerich DF. Intracerebral transplantation of porcine choroid plexus provides structural and functional neuroprotection in a rodent model of stroke. Stroke. 2004;35:2206–2210. doi: 10.1161/01.STR.0000138954.25825.0b. PubMed DOI

Borlongan CV, Skinner SJM, Geaney M, Vasconcellos AV, Elliott RB, Emerich DF. CNS grafts of rat choroid plexus protect against cerebral ischemia in adult rats. NeuroReport. 2004;15:1543–1547. doi: 10.1097/01.wnr.0000133298.84901.cf. PubMed DOI

Matsumoto N, Taguchi A, Kitayama H, Watanabe Y, Ohta M, Yoshihara T, et al. Transplantation of cultured choroid plexus epithelial cells via cerebrospinal fluid shows prominent neuroprotective effects against acute ischemic brain injury in the rat. Neurosci Lett. 2010;469:283–288. doi: 10.1016/j.neulet.2009.09.060. PubMed DOI

Maxwell WL, Hardy IG, Watt C, McGadey J, Graham DI, Adams JH, et al. Changes in the choroid plexus, responses by intrinsic epiplexus cells and recruitment from monocytes after experimental head acceleration injury in the non-human primate. Acta Neuropathol. 1992;84:78–84. doi: 10.1007/bf00427218. PubMed DOI

Sharma HS, Zimmermann-Meinzingen S, Johanson CE. Cerebrolysin reduces blood–cerebrospinal fluid barrier permeability change, brain pathology, and functional deficits following traumatic brain injury in the rat. Ann NY Acad Sci. 2010;1199:125–137. doi: 10.1111/j.1749-6632.2009.05329.x. PubMed DOI

Kaur C, Singh J, Lim MK, Ng BL, Yap EP, Ling EA. Studies of the choroid plexus and its associated epiplexus cells in the lateral ventricles of rats following an exposure to a single non-penetrative blast. Arch Histol Cytol. 1996;59:239–248. doi: 10.1679/aohc.59.239. PubMed DOI

Szmydynger-Chodobska J, Strazielle N, Zink BJ, Ghersi-Egea J-F, Chodobski A. The role of the choroid plexus in neutrophil invasion after traumatic brain injury. J Cereb Blood Flow Meta. 2009;29:1503–1516. doi: 10.1038/jcbfm.2009.71. PubMed DOI PMC

Helmy A, Carpenter KL, Menon DK, Pickard JD, Hutchinson PJ. The cytokine response to human traumatic brain injury: temporal profiles and evidence for cerebral parenchymal production. J Cereb Blood Flow Metab. 2011 doi: 10.1038/jcbfm.2010.142. PubMed DOI PMC

Semple BD, Bye N, Rancan M, Ziebell JM, Morganti-Kossmann MC. Role of CCL2 (MCP-1) in Traumatic Brain Injury (TBI): evidence from severe TBI patients and CCL2−/− mice. J Cereb Blood Flow Metab. 2010;30:769–782. doi: 10.1038/jcbfm.2009.262. PubMed DOI PMC

Shechter R, Miller O, Yovel G, Rosenzweig N, London A, Ruckh J, et al. Recruitment of beneficial M2 macrophages to injured spinal cord is orchestrated by remote brain choroid plexus. Immunity. 2013;38:555–569. doi: 10.1016/j.immuni.2013.02.012. PubMed DOI PMC

Joukal M, Klusáková I, Solár P, Kuklová A, Dubový P. Cellular reactions of the choroid plexus induced by peripheral nerve injury. Neurosci Lett. 2016;628:73–77. doi: 10.1016/j.neulet.2016.06.019. PubMed DOI

Brkic M, Balusu S, Van Wonterghem E, Gorlé N, Benilova I, Kremer A, et al. Amyloid β oligomers disrupt blood-CSF barrier integrity by activating matrix metalloproteinases. J Neurosci. 2015;35:12766–12778. doi: 10.1523/JNEUROSCI.0006-15.2015. PubMed DOI PMC

Krzyzanowska A, Carro E. Pathological alteration in the choroid plexus of Alzheimer’s disease: implication for new therapy approaches. Front Pharmacol. 2012;3:75. doi: 10.3389/fphar.2012.00075. PubMed DOI PMC

Prineas JW, Parratt JDE, Kirwan PD. Fibrosis of the choroid plexus filtration membrane. J Neuropathol Exp Neurol. 2016;75:855–867. doi: 10.1093/jnen/nlw061. PubMed DOI PMC

Deczkowska A, Baruch K, Schwartz M. Type I/II interferon balance in the regulation of brain physiology and pathology. Trends Immunol. 2016;7:181–192. doi: 10.1016/j.it.2016.01.006. PubMed DOI

Mesquita SD, Ferreira AC, Gao F, Coppola G, Geschwind DH, Sousa JC, et al. The choroid plexus transcriptome reveals changes in type I and II interferon responses in a mouse model of Alzheimer’s disease. Brain Behav Immun. 2015;49:280–292. doi: 10.1016/j.bbi.2015.06.008. PubMed DOI

Alvira-Botero X, Carro EM. Clearance of amyloid-β peptide across the choroid plexus in Alzheimer’s disease. Current Aging Science. 2010;3:219–229. doi: 10.2174/1874609811003030219. PubMed DOI

Spuch C, Antequera D, Pascual C, Abilleira S, Blanco M, Moreno-Carretero MJ, et al. Soluble megalin is reduced in cerebrospinal fluid samples of Alzheimer’s Disease patients. Front Cell Neurosci. 2015 doi: 10.3389/fncel.2015.00134. PubMed DOI PMC

Deane R, Bell R, Sagare A, Zlokovic B. Clearance of amyloid-β peptide across the blood–brain barrier: implication for therapies in Alzheimer’s disease. CNS Neurol Disord Drug Targets. 2009;8:16–30. doi: 10.2174/187152709787601867. PubMed DOI PMC

Kaur C, Rathnasamy G, Ling E-A. The choroid plexus in healthy and diseased brain. J Neuropathol Exp Neurol. 2016;75:198–213. doi: 10.1093/jnen/nlv030. PubMed DOI

Ocheltree SM, Shen H, Hu Y, Xiang J, Keep RF, Smith DE. Role of PEPT2 in the choroid plexus uptake of glycylsarcosine and 5-aminolevulinic acid: studies in wild-type and null mice. Pharm Res. 2004;21:1680–1685. doi: 10.1023/B:PHAM.0000041465.89254.05. PubMed DOI

Varatharaj A, Galea I. The blood–brain barrier in systemic inflammation. Brain Behav Immun. 2017;60:1–12. doi: 10.1016/j.bbi.2016.03.010. PubMed DOI

González-Marrero I, Giménez-Llort L, Johanson CE, Carmona-Calero EM, Castañeyra-Ruiz L, Brito-Armas JM, et al. Choroid plexus dysfunction impairs beta-amyloid clearance in a triple transgenic mouse model of Alzheimer’s disease. Front Cell Neurosci. 2015 doi: 10.3389/fncel.2015.00017. PubMed DOI PMC

Spector R, Johanson CE. Sustained choroid plexus function in human elderly and Alzheimer’s disease patients. Fluids Barriers CNS. 2013;10:28. doi: 10.1186/2045-8118-10-28. PubMed DOI PMC

Perez-Gracia E, Blanco R, Carmona M, Carro E, Ferrer I. Oxidative stress damage and oxidative stress responses in the choroid plexus in Alzheimer’s disease. Acta Neuropathol. 2009;118:497–504. doi: 10.1007/s00401-009-0574-4. PubMed DOI

Marques F, Sousa JC, Brito MA, Pahnke J, Santos C, Correia-Neves M, et al. The choroid plexus in health and in disease: dialogues into and out of the brain. Neurobiol Dis. 2017;107:32–40. doi: 10.1016/j.nbd.2016.08.011. PubMed DOI

Serot J-M, Béné M-C, Faure GC. Choroid plexus, aging of the brain, and Alzheimer’s disease. Front Biosci. 2003;8:s515–s521. doi: 10.2741/1085. PubMed DOI

Serot JM, Béné MC, Foliguet B, Faure GC. Morphological alterations of the choroid plexus in late-onset Alzheimer’s disease. Acta Neuropathol. 2000;99:105–108. doi: 10.1007/pl00007412. PubMed DOI

Chalbot S, Zetterberg H, Blennow K, Fladby T, Andreasen N, Grundke-Iqbal I, et al. Blood–cerebrospinal fluid barrier permeability in Alzheimer’s disease. J Alzheimers Dis. 2011;25:505–515. doi: 10.3233/JAD-2011-101959. PubMed DOI PMC

Johanson CE, Stopa EG, Daiello L, de la Monte S, Keane M, Ott BR. Disrupted blood-CSF barrier to urea and creatinine in mild cognitive impairment and Alzheimer’s disease. J Alzheimers Dis Parkinsonism. 2018;08:435. doi: 10.4172/2161-0460.1000435. DOI

Masseguin C, LePanse S, Corman B, Verbavatz JM, Gabrion J. Aging affects choroidal proteins involved in CSF production in Sprague-Dawley rats. Neurobiol Aging. 2005;26:917–927. doi: 10.1016/j.neurobiolaging.2004.07.013. PubMed DOI

Kant S, Stopa EG, Johanson CE, Baird A, Silverberg GD. Choroid plexus genes for CSF production and brain homeostasis are altered in Alzheimer’s disease. Fluids Barriers CNS. 2018;15:34. doi: 10.1186/s12987-018-0120-7. PubMed DOI PMC

Nardo AD, Moya KL, Arnaud K, Prochiantz A. Inhibition of the synthesis of beta-app or of the activity of the a-beta peptide in the choroid plexus. 2018. patent/US20180142012A1/en.

Bolos M, Antequera D, Aldudo J, Kristen H, Bullido MJ, Carro E. Choroid plexus implants rescue Alzheimer’s disease-like pathologies by modulating amyloid-β degradation. Cell Mol Life Sci. 2014;71:2947–2955. doi: 10.1007/s00018-013-1529-4. PubMed DOI PMC

Bates CA, Fu S, Ysselstein D, Rochet J-C, Zheng W. Expression and transport of α-synuclein at the blood–cerebrospinal fluid barrier and effects of manganese exposure. ADMET DMPK. 2015;3:15–33. doi: 10.5599/admet.3.1.159. PubMed DOI PMC

Bates CA, Zheng W. Brain disposition of α-synuclein: roles of brain barrier systems and implications for Parkinson’s disease. Fluids Barriers CNS. 2014;11:17. doi: 10.1186/2045-8118-11-17. PubMed DOI PMC

Stopa EG, Tanis KQ, Miller MC, Nikonova EV, Podtelezhnikov AA, Finney EM, et al. Comparative transcriptomics of choroid plexus in Alzheimer’s disease, frontotemporal dementia and Huntington’s disease: implications for CSF homeostasis. Fluids Barriers CNS. 2018;15:18. doi: 10.1186/s12987-018-0102-9. PubMed DOI PMC

Borlongan CV, Thanos CG, Skinner SJM, Geaney M, Emerich DF. Transplants of encapsulated rat choroid plexus cells exert neuroprotection in a rodent model of huntington’s disease. Cell Transplant. 2007;16:987–992. doi: 10.3727/000000007783472426. PubMed DOI

Engelhardt B, Wolburg-Buchholz K, Wolburg H. Involvement of the choroid plexus in central nervous system inflammation. Microsc Res Tech. 2001;52:112–129. doi: 10.1002/1097-0029(20010101)52:1<112::AID-JEMT13>3.0.CO;2-5. PubMed DOI

Kivisäkk P, Mahad DJ, Callahan MK, Trebst C, Tucky B, Wei T, et al. Human cerebrospinal fluid central memory CD4+ T cells: evidence for trafficking through choroid plexus and meninges via P-selectin. PNAS. 2003;100:8389–8394. doi: 10.1073/pnas.1433000100. PubMed DOI PMC

Kunis G, Baruch K, Rosenzweig N, Kertser A, Miller O, Berkutzki T, et al. IFN-γ-dependent activation of the brain’s choroid plexus for CNS immune surveillance and repair. Brain. 2013;136:3427–3440. doi: 10.1093/brain/awt259. PubMed DOI

Vercellino M, Votta B, Condello C, Piacentino C, Romagnolo A, Merola A, et al. Involvement of the choroid plexus in multiple sclerosis autoimmune inflammation: a neuropathological study. J Neuroimmunol. 2008;199:133–141. doi: 10.1016/j.jneuroim.2008.04.035. PubMed DOI

Wilson EH, Weninger W, Hunter CA. Trafficking of immune cells in the central nervous system. J Clin Invest. 2010;120:1368–1379. doi: 10.1172/JCI41911. PubMed DOI PMC

Reboldi A, Coisne C, Baumjohann D, Benvenuto F, Bottinelli D, Lira S, et al. C–C chemokine receptor 6-regulated entry of T H -17 cells into the CNS through the choroid plexus is required for the initiation of EAE. Nat Immunol. 2009;10:514–523. doi: 10.1038/ni.1716. PubMed DOI

Strominger I, Elyahu Y, Berner O, Reckhow J, Mittal K, Nemirovsky A, et al. The choroid plexus functions as a niche for T-cell stimulation within the central nervous system. Front Immunol. 2018;9:1066. doi: 10.3389/fimmu.2018.01066. PubMed DOI PMC

Mills JH, Alabanza LM, Mahamed DA, Bynoe MS. Extracellular adenosine signaling induces CX3CL1 expression in the brain to promote experimental autoimmune encephalomyelitis. J Neuroinflammation. 2012;9:193. doi: 10.1186/1742-2094-9-193. PubMed DOI PMC

Junker A, Hohlfeld R, Meinl E. The emerging role of microRNAs in multiple sclerosis. Nat Rev Neurol. 2011;7:56–59. doi: 10.1038/nrneurol.2010.179. PubMed DOI

Wu GF, Alvarez E. The immuno-pathophysiology of multiple sclerosis. Neurol Clin. 2011;29:257–278. doi: 10.1016/j.ncl.2010.12.009. PubMed DOI PMC

Murugesan N, Paul D, Lemire Y, Shrestha B, Ge S, Pachter JS. Active induction of experimental autoimmune encephalomyelitis by MOG35-55 peptide immunization is associated with differential responses in separate compartments of the choroid plexus. Fluids Barriers CNS. 2012;9:15. doi: 10.1186/2045-8118-9-15. PubMed DOI PMC

Parratt JDE, Prineas JW. Neuromyelitis optica: a demyelinating disease characterized by acute destruction and regeneration of perivascular astrocytes. Mult Scler. 2010;16:1156–1172. doi: 10.1177/1352458510382324. PubMed DOI

Kunis G, Baruch K, Miller O, Schwartz M. Immunization with a myelin-derived antigen activates the brain’s choroid plexus for recruitment of immunoregulatory cells to the cns and attenuates disease progression in a mouse model of ALS. J Neurosci. 2015;35:6381–6393. doi: 10.1523/JNEUROSCI.3644-14.2015. PubMed DOI PMC

Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016;131:803–820. doi: 10.1007/s00401-016-1545-1. PubMed DOI

McComb RD, Burger PC. Choroid plexus carcinoma: report of a case with lmmunohistochemical and ultrastructural observations. Cancer. 1983;51:470–475. doi: 10.1002/1097-0142(19830201)51:3<470::AID-CNCR2820510319>3.0.CO;2-K. PubMed DOI

Muscatello LV, Avallone G, Serra F, Seuberlich T, Mandara MT, Sisó S, et al. Glomeruloid microvascular proliferation, desmoplasia, and high proliferative index as potential indicators of high grade canine choroid plexus tumors. Vet Pathol. 2018;55:391–401. doi: 10.1177/0300985817754124. PubMed DOI

Megerian CA, Pilch BZ, Bhan AK, McKenna MJ. Differential expression of transthyretin in papillary tumors of the endolymphatic sac and choroid plexus. Laryngoscope. 1997;107:216–221. doi: 10.1097/00005537-199702000-00014. PubMed DOI

Paulus W, Jänisch W. Clinicopathologic correlations in epithelial choroid plexus neoplasms: a study of 52 cases. Acta Neuropathol. 1990;80:635–641. doi: 10.1007/BF00307632. PubMed DOI

Rickert CH, Paulus W. Tumors of the choroid plexus. Microsc Res Tech. 2001;52:104–111. doi: 10.1002/1097-0029(20010101)52:1<104::AID-JEMT12>3.0.CO;2-3. PubMed DOI

Pienkowska M, Choufani S, Turinsky AL, Guha T, Merino DM, Novokmet A, et al. DNA methylation signature is prognostic of choroid plexus tumor aggressiveness. Clin Epigenetics. 2019;11:117. doi: 10.1186/s13148-019-0708-z. PubMed DOI PMC

Longatti P, Basaldella L, Orvieto E, Dei Tos A, Martinuzzi A. Aquaporin(s) expression in choroid plexus tumours. Pediatr Neurosurg. 2006;42:228–233. doi: 10.1159/000092359. PubMed DOI

Fairburn B. Choroid plexus papilloma and its relation to hydrocephalus. J Neurosurg. 1960;17:166–171. doi: 10.3171/jns.1960.17.1.0166. PubMed DOI

Fujimura M, Onuma T, Kameyama M, Motohashi O, Kon H, Yamamoto K, et al. Hydrocephalus due to cerebrospinal fluid overproduction by bilateral choroid plexus papillomas. Childs Nerv Syst. 2004;20:485–488. doi: 10.1007/s00381-003-0889-8. PubMed DOI

Aydın M, Kanat A, Karaavci C, Sahin H, Ozmen S. First demonstration water-filled vesicles of choroid plexus tumors. J Craniofac Surg. 2019 doi: 10.1097/scs.0000000000005735. PubMed DOI

Hasselblatt M, Mertsch S, Koos B, Riesmeier B, Stegemann H, Jeibmann A, et al. TWIST-1 Is overexpressed in neoplastic choroid plexus epithelial cells and promotes proliferation and invasion. Cancer Res. 2009;69:2219–2223. doi: 10.1158/0008-5472.CAN-08-3176. PubMed DOI PMC

Puisieux A, Valsesia-Wittmann S, Ansieau S. A twist for survival and cancer progression. Br J Cancer. 2006;94:13–17. doi: 10.1038/sj.bjc.6602876. PubMed DOI PMC

Shannon ML, Fame RM, Chau KF, Dani N, Calicchio ML, Géléoc GS, et al. Mice expressing Myc in neural precursors develop choroid plexus and ciliary body tumors. Am J Pathol. 2018;188:1334–1344. doi: 10.1016/j.ajpath.2018.02.009. PubMed DOI PMC

Merve A, Zhang X, Pomella N, Acquati S, Hoeck JD, Dumas A, et al. c-MYC overexpression induces choroid plexus papillomas through a T-cell mediated inflammatory mechanism. Acta Neuropathol Commun. 2019;7:95. doi: 10.1186/s40478-019-0739-x. PubMed DOI PMC

Ide T, Uchida K, Kikuta F, Suzuki K, Nakayama H. Immunohistochemical characterization of canine neuroepithelial tumors. Vet Pathol. 2010;47:741–750. doi: 10.1177/0300985810363486. PubMed DOI

Nentwig A, Higgins RJ, Francey T, Doherr M, Zurbriggen A, Oevermann A. Aberrant E-cadherin, β-catenin, and glial fibrillary acidic protein (GFAP) expression in canine choroid plexus tumors. J Vet Diagn Invest. 2012;24:14–22. doi: 10.1177/1040638711425940. PubMed DOI

Reginato A, Girolami D, Menchetti L, Foiani G, Mandara MT. E-cadherin, N-cadherin expression and histologic characterization of canine choroid plexus tumors. Vet Pathol. 2016;53:788–791. doi: 10.1177/0300985815620844. PubMed DOI

Miller AD, Miller CR, Rossmeisl JH. Canine primary intracranial cancer: a clinicopathologic and comparative review of glioma, meningioma, and choroid plexus tumors. Front Oncol. 2019;9:1151. doi: 10.3389/fonc.2019.01151. PubMed DOI PMC

Beatty RA. Malignant melanoma of the choroid plexus epithelium: case report. J Neurosurg. 1972;36:344–347. doi: 10.3171/jns.1972.36.3.0344. PubMed DOI

Cecchi PC, Billio A, Colombetti V, Rizzo P, Ricci UM, Schwarz A. Primary high-grade B-cell lymphoma of the choroid plexus. Clin Neurol Neurosurg. 2008;110:75–79. doi: 10.1016/j.clineuro.2007.08.019. PubMed DOI

Schackert G, Simmons RD, Buzbee TM, Hume DA, Fidler IJ. Macrophage infiltration into experimental brain metastases: occurrence through an intact blood–brain barrier. J Natl Cancer Inst. 1988;80:1027–1034. doi: 10.1093/jnci/80.13.1027. PubMed DOI

Terasaki M, Abe T, Tajima Y, Fukushima S, Hirohata M, Shigemori M. Primary choroid plexus T-cell lymphoma and multiple aneurysms in the CNS. Leukemia Lymphoma. 2006;47:1680–1682. doi: 10.1080/10428190600612503. PubMed DOI

Kim S, Hwang Y, Lee D, Webster MJ. Transcriptome sequencing of the choroid plexus in schizophrenia. Transl Psychiatry. 2016;6:e964. doi: 10.1038/tp.2016.229. PubMed DOI PMC

Lizano P, Lutz O, Ling G, Lee AM, Eum S, Bishop JR, et al. Association of choroid plexus enlargement with cognitive, inflammatory, and structural phenotypes across the psychosis spectrum. Am J Psychiatry. 2019;176:564–572. doi: 10.1176/appi.ajp.2019.18070825. PubMed DOI PMC

Sathyanesan M, Girgenti MJ, Banasr M, Stone K, Bruce C, Guilchicek E, et al. A molecular characterization of the choroid plexus and stress-induced gene regulation. Transl Psychiatry. 2012;2:e139. doi: 10.1038/tp.2012.64. PubMed DOI PMC

Simard PF, Tosun C, Melnichenko L, Ivanova S, Gerzanich V, Simard JM. Inflammation of the choroid plexus and ependymal layer of the ventricle following intraventricular hemorrhage. Transl Stroke Res. 2011;2:227–231. doi: 10.1007/s12975-011-0070-8. PubMed DOI PMC

Johanson C, Stopa E, Baird A, Sharma H. Traumatic brain injury and recovery mechanisms: peptide modulation of periventricular neurogenic regions by the choroid plexus–CSF nexus. J Neural Transm. 2011;118:115–133. doi: 10.1007/s00702-010-0498-0. PubMed DOI PMC

Wen GY, Wisniewski HM, Kascsak RJ. Biondi ring tangles in the choroid plexus of Alzheimer’s disease and normal aging brains: a quantitative study. Brain Res. 1999;832:40–46. doi: 10.1016/S0006-8993(99)01466-3. PubMed DOI

Breaking boundaries: role of the brain barriers in metastatic process

Paclitaxel triggers molecular and cellular changes in the choroid plexus

The circadian clock in the choroid plexus drives rhythms in multiple cellular processes under the control of the suprachiasmatic nucleus

Inflammatory changes in the choroid plexus following subarachnoid hemorrhage: the role of innate immune receptors and inflammatory molecules

Basic Analysis of the Cerebrospinal Fluid: An Important Framework for Laboratory Diagnostics of the Impairment of the Central Nervous System

Current Chemical, Biological, and Physiological Views in the Development of Successful Brain-Targeted Pharmaceutics

Subarachnoid Hemorrhage Increases Level of Heme Oxygenase-1 and Biliverdin Reductase in the Choroid Plexus