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The Blood–Brain Barrier: An Introduction to Its Structure and Function

  • Anne MahringerEmail author
  • Melanie Ott
  • Gert Fricker
Chapter
Part of the Topics in Medicinal Chemistry book series (TMC, volume 10)

Abstract

The blood-brain barrier (BBB) formed by the brains microvascular system is impermeable for most therapeutically used compounds and overcoming this barrier remains to be one of the big challenges in modern medicine. It is composed of highly specialized endothelial cells, which are surrounded by pericytes and a basal membrane. Together with nearby astrocytes and neurons they constitute the so-called neurovascular unit, which restricts substance transfer from blood to brain and vice versa and maintains the cerebral ion homeostasis. Chapters of this book describe the discovery of the BBB, its evolutionary development as well as the cellular and molecular mechanisms, which underlay its structure and function in health and disease. The organization of tight junctional complexes or specific transport processes at the BBB will be addressed as well as methods to investigate BBB function in vitro and in vivo. Changes in the barrier function under several diseases conditions such as stroke or inflammation will be discussed as well as approaches to overcome the barrier by colloidal carriers or ultrasound.

Keywords

Blood–brain barrier Neurovascular unit Morphology Transporter 

References

  1. 1.
    Pardridge WM (2005) NeuroRx 2:3–14Google Scholar
  2. 2.
    Pardridge WM (2007) Drug Discov Today 12:54–61Google Scholar
  3. 3.
    Ehrlich P (1885) Das Sauerstoffbedürfnis des Organismus. In: Eine Farbenanalytische Studie, Hirschwald, BerlinGoogle Scholar
  4. 4.
    Ehrlich P (1904) Ueber die Beziehungen von chemischer Constitution, Verteilung und pharmakologischer Wirkung. In: Gesammelte Arbeiten zur Immunitaetsforschung, Hirschwald, Berlin, p 574Google Scholar
  5. 5.
    Bield A, Kraus R (1898) Zhl Inn Med 19:1185–1200Google Scholar
  6. 6.
    Goldmann E (1913) Abh Preuss Akad Wiss Physik-Math 1:1–60Google Scholar
  7. 7.
    Goldmann E (1909) Die äussere und innere Sekretion des gesunden und kranken Organismus im Lichte der “vitalen” Färbung. Beitr Klin Chir 64:192–265Google Scholar
  8. 8.
    Lewandowsky M (1900) Z Klin Med 40:480–484Google Scholar
  9. 9.
    Loewit M (1881) Zeitschr Heilkunde 2:459–495Google Scholar
  10. 10.
    Roux MME, Borrel A (1898) Ann Inst Pasteur 4:225–238Google Scholar
  11. 11.
    Stern L (1921) Schweiz Arch Neurol 8:215–232Google Scholar
  12. 12.
    Behnsen G (1926) Zeitschr Zellforsch 4:515–572Google Scholar
  13. 13.
    Spatz H (1933) Arch Psych 101:267–358Google Scholar
  14. 14.
    Walter FK (1929) Die Blut-Liquorschranke – eine physiologische und klinische Studie. Georg Thieme, StuttgartGoogle Scholar
  15. 15.
    Walter FK (1933) Arch Psych 101:195–230Google Scholar
  16. 16.
    Foertig H (1929) Die Bluthirnschranke. Zentralblatt für Haut- und Geschlechtskrankheiten 28:369–398Google Scholar
  17. 17.
    Broman T (1941) Acta Psychiatr 16:1–25Google Scholar
  18. 18.
    Friedemann U (1942) Physiol Rev 22:125–145Google Scholar
  19. 19.
    Krogh A (1946) Proc Royal Soc Med 133:140–200Google Scholar
  20. 20.
    Van Harreveld A, Collewijn H, Malhotra SK (1966) Am J Physiol 210:251–256Google Scholar
  21. 21.
    Brightman MW, Reese TS (1969) J Cell Biol 40:648–677Google Scholar
  22. 22.
    Reese TS, Karnovsky MJ (1967) J Cell Biol 34:207–217Google Scholar
  23. 23.
    Zlokovic BV (2008) Neuron 57:178–201Google Scholar
  24. 24.
    Oldendorf WH (1971) Am J Physiol 221:1629–1639Google Scholar
  25. 25.
    Nagy Z, Peters H, Huttner I (1984) Lab Invest 50:313–322Google Scholar
  26. 26.
    Shivers RR, Betz AL, Goldstein GW (1984) Brain Res 324:313–322Google Scholar
  27. 27.
    Butt AM, Jones HC, Abbott NJ (1990) J Physiol 429:47–62Google Scholar
  28. 28.
    Crone C, Olsen SP (1982) Brain Res 241:49–55Google Scholar
  29. 29.
    Weiler-Güttler H, Zinke H, Möckel B, Frey A, Gassen HG (1989) Biol Chem Hoppe Seyler 370:467–473Google Scholar
  30. 30.
    Stern L, Gautier R (1921) Arch Int Physiol 17:138–192Google Scholar
  31. 31.
    Stern L, Gautier R (1922) Arch Int Physiol 17:391–448Google Scholar
  32. 32.
    Schinkel AH (2001) Adv Exp Med Biol 500:365–372Google Scholar
  33. 33.
    Miller DS (2010) Trends Pharmacol Sci 31:246–254Google Scholar
  34. 34.
    Abbott NJ (1992) In: Bradbury MWB (ed) Physiology and pharmacology of the blood–brain barrier. Springer, London, pp 371–396Google Scholar
  35. 35.
    Bundgaard M, Abbott NJ (2008) Glia 56:699–708Google Scholar
  36. 36.
    Cserr HF, Bundgaard M (1984) Am J Physiol 246:R277–R288Google Scholar
  37. 37.
    Begley DJ, Brightman MW (2003) Prog Drug Res 61:39–78Google Scholar
  38. 38.
    Zlokovic BV (2005) Trends Neurosci 28:202–208Google Scholar
  39. 39.
    Rengachary SS (2005) Intracranial pressure, cerebral edema, and brain herniation. In: Rengachary SS, Ellenbogen RG (eds) Principles of neurosurgery. Elsevier Mosby, New York, pp 65–70Google Scholar
  40. 40.
    Fenstermacher J, Gross P, Sposito N, Acuff V, Pettersen S, Gruber K (1988) Ann NY Acad Sci 529:21–30Google Scholar
  41. 41.
    Kniesel U, Wolburg H (2000) Cell Mol Neurobiol 20:57–76Google Scholar
  42. 42.
    el-Bacha RS, Minn A (1999) Cell Mol Biol 45:15–23Google Scholar
  43. 43.
    Minn A et al (1991) Brain Res Brain Res Rev 116:65–82Google Scholar
  44. 44.
    Oldendorf WH, Cornford ME, Brown WJ (1977) Ann Neurol 1:409–417Google Scholar
  45. 45.
    Sedlakova R, Shivers RR, Del Maestro RF (1999) J Submicrosc Cytol Pathol 31:149–161Google Scholar
  46. 46.
    Zlokovic BV, Apuzzo ML (1998) Neurosurgery 43(4):877–878Google Scholar
  47. 47.
    Rodríguez-Baeza A, Reina-de la Torre F, Poca A, Martí M, Garnacho A (2003) Anat Rec A Discov Mol Cell Evol Biol 273(1):583–593Google Scholar
  48. 48.
    Armulik A, Abramsson A, Betsholtz C (2005) Circ Res 97:512–523Google Scholar
  49. 49.
    Tagami M, Nara Y, Kubota A, Fujino H, Yamori Y (1990) Stroke 21:1064–1071Google Scholar
  50. 50.
    Dore-Duffy P (2008) Curr Pharm Des 14:1581–1593Google Scholar
  51. 51.
    Allt G, Lawrenson JG (2001) Cells Tissues Organs 169:1–11Google Scholar
  52. 52.
    Fernandez-Klett F, Offenhauser N, Dirnagl U, Priller J, Lindauer U (2010) Proc Natl Acad Sci USA 107:22290–22295Google Scholar
  53. 53.
    Peppiatt CM, Howarth C, Mobbs P, Attwell D (2006) Nature 443:700–704Google Scholar
  54. 54.
    Thomas WE (1999) Brain Res Brain Res Rev 31:42–57Google Scholar
  55. 55.
    Rucker HK et al (2000) Brain Res Bull 51:363–369Google Scholar
  56. 56.
    Balabanov R et al (1996) Microvasc Res 52:127–142Google Scholar
  57. 57.
    Mato M et al (1984) Experientia 40:399–402Google Scholar
  58. 58.
    Dore-Duffy P, La Manna JC (2007) Antioxid Redox Signal 9:1363–1372Google Scholar
  59. 59.
    von Tell D, Armulik A, Betsholtz C (2006) Exp Cell Res 312:623–629Google Scholar
  60. 60.
    Hori S, Ohtsuki S, Hosoya K, Nakashima E, Terasaki T (2004) J Neurochem 89(2):503–513Google Scholar
  61. 61.
    Allende ML, Proia RL (2002) Biochim Biophys Acta 1582:222–227Google Scholar
  62. 62.
    Sato Y (1995) J Atheroscler Thromb 2:24–29Google Scholar
  63. 63.
    Chekenya M, Enger PØ, Thorsen F, Tysnes BB, Al-Sarraj S, Read TA, Furmanek T, Mahesparan R, Levine JM, Butt AM, Pilkington GJ, Bjerkvig R (2002) Neuropathol Appl Neurobiol 28:367–380Google Scholar
  64. 64.
    Najbauer J, Huszthy PC, Barish ME, Garcia E, Metz MZ, Myers SM, Gutova M, Frank RT, Miletic H, Kendall SE, Glackin CA, Bjerkvig R, Aboody KS (2012) PLoS One 7:e35150Google Scholar
  65. 65.
    Nakagawa S, Castro V, Toborek M (2012) J Cell Mol Med 16(12):2950–2957Google Scholar
  66. 66.
    Wyss-Coray T, Lin C, Sanan DA, Mucke L, Masliah E (2000) Am J Pathol 156:139–150Google Scholar
  67. 67.
    Alcendor DJ, Charest AM, Zhu WQ, Vigil HE, Knobel SM (2012) J Neuroinflammation 18:95Google Scholar
  68. 68.
    Yemisci M, Gursoy-Ozdemir Y, Vural A, Can A, Topalkara K, Dalkara T (2009) Nat Med 15:1031–1037Google Scholar
  69. 69.
    Szpak GM, Lewandowska E, Wierzba-Bobrowicz T, Bertrand E, Pasennik E, Mendel T, Stepien T, Leszczynska A, Rafalowska J (2007) Folia Neuropathol 45:192–204Google Scholar
  70. 70.
    Wisniewski HM, Wegiel J, Wang KC, Lach B (1992) Acta Neuropathol 84:117–127Google Scholar
  71. 71.
    Bell RD, Zlokovic BV (2009) Acta Neuropathol 118:103–113Google Scholar
  72. 72.
    Bell RD, Deane R, Chow N, Long X, Sagare A, Singh I, Streb JW, Guo H, Rubio A, Van Nostrand W, Miano JM, Zlokovic BV (2009) Nat Cell Biol 11:143–153Google Scholar
  73. 73.
    Dalkara T, Gursoy-Ozdemir Y, Yemisci M (2011) Acta Neuropathol 122:1–9Google Scholar
  74. 74.
    Zlokovic BV (2010) Nat Med 16:1370–1371Google Scholar
  75. 75.
    Davson H, Oldendorf WH (1967) Proc R Soc Med 60:326–329Google Scholar
  76. 76.
    Neuhaus J, Risau W, Wolburg H (1991) Ann NY Acad Sci 633:578–580Google Scholar
  77. 77.
    Tao-Cheng JH, Nagy Z, Brightman MW (1987) J Neurosci 7:3293–3299Google Scholar
  78. 78.
    Maxwell K, Berliner JA, Cancilla PA (1987) Brain Res 410:309–314Google Scholar
  79. 79.
    Willis CL, Nolan CC, Reith SN, Lister T, Prior MJ, Guerin CJ, Mavroudis G, Ray DE (2004) Glia 45:325–337Google Scholar
  80. 80.
    Braet K, Paemeleire K, D'Herde K, Sanderson MJ, Leybaert L (2001) Eur J Neurosci 13:79–91Google Scholar
  81. 81.
    Paemeleire K (2002) Acta Neurol Belg 102:153–157Google Scholar
  82. 82.
    Zonta M, Angulo MC, Gobbo S, Rosengarten B, Hossmann KA, Pozzan T, Carmignoto G (2003) Nat Neurosci 6:43–50Google Scholar
  83. 83.
    Ballabh P, Braun A, Nedergaard M (2004) Neurobiol Dis 16:1–13Google Scholar
  84. 84.
    Tran ND, Correale J, Schreiber SS, Fisher M (1999) Stroke 30:1671–1678Google Scholar
  85. 85.
    Utsumi H, Chiba H, Kamimura Y, Osanai M, Igarashi Y, Tobioka H, Mori M, Sawada N (2000) Am J Physiol Cell Physiol 279:C361–C368Google Scholar
  86. 86.
    Mi H, Haeberle H, Barres BA (2001) J Neurosci 21:1538–1547Google Scholar
  87. 87.
    Yoder EJ (2002) Glia 38:137–145Google Scholar
  88. 88.
    Rash JE, Yasumura T, Hudson CS, Agre P, Nielsen S (1998) Proc Natl Acad Sci 95:11981–11986Google Scholar
  89. 89.
    Roy CS, Sherrington CS (1890) J Physiol 11:85–158Google Scholar
  90. 90.
    Nishijima T, Piriz J, Duflot S, Fernandez AM, Gaitan G, Gomez-Pinedo U, Verdugo JM, Leroy F, Soya H, Nuñez A, Torres-Aleman I (2010) Neuron 67:834–846Google Scholar
  91. 91.
    Stewart PA, Wiley MJ (1981) Dev Biol 84:183–192Google Scholar
  92. 92.
    Ben-Menachem E, Johansson BB, Svensson TH (1982) J Neural Transm 53:159–167Google Scholar
  93. 93.
    Cohen Z, Molinatti G, Hamel E (1997) J Cereb Blood Flow Metab 17:894–904Google Scholar
  94. 94.
    Cohen Z, Bonvento G, Lacombe P, Hamel E (1996) Prog Neurobiol 50:335–362Google Scholar
  95. 95.
    Tong XK, Hamel E (1999) Neuroscience 92:163–175Google Scholar
  96. 96.
    Vaucher E, Hamel E (1995) J Neurosci 15:7427–7441Google Scholar
  97. 97.
    Vaucher E, Tong XK, Cholet N, Lantin S, Hamel E (2000) J Comp Neurol 421:161–171Google Scholar
  98. 98.
    Kobayashi H, Magnoni MS, Govoni S, Izumi F, Wada A, Trabucchi M (1985) Experientia 41:427–434Google Scholar
  99. 99.
    Farkas E, Luiten PG (2001) Prog Neurobiol 64:575–611Google Scholar
  100. 100.
    Hynes RO (1992) Cell 69:11–25Google Scholar
  101. 101.
    Savettieri G, Di Liegro I, Catania C, Licata L, Pitarresi GL, D'Agostino S, Schiera G, De Caro V, Giandalia G, Giannola LI et al (2000) Neuroreport 11:1081–1084Google Scholar
  102. 102.
    Tilling T, Korte D, Hoheisel D, Galla HJ (1998) J Neurochem 71:1151–1157Google Scholar
  103. 103.
    Rascher G, Fischmann A, Kröger S, Duffner F, Grote EH, Wolburg H (2002) Acta Neuropathol 104:85–91Google Scholar
  104. 104.
    Rosenberg GA, Estrada E, Kelley RO, Kornefeld M (1993) Neurosci Lett 160:117–119Google Scholar
  105. 105.
    Tilling T, Engelbertz C, Decker S, Korte D, Hüwel S, Galla HJ (2002) Cell Tissue Res 310:19–29Google Scholar
  106. 106.
    Schulze C, Firth JA (1993) J Cell Sci 104:773–782Google Scholar
  107. 107.
    Vorbrodt AW, Dobrogowska DH (2003) Brain Res Brain Res Rev 42:221–242Google Scholar
  108. 108.
    Wolburg H, Lippoldt A (2002) Vascul Pharmacol 38:323–337Google Scholar
  109. 109.
    Bazzoni G, Dejana E (2004) Physiol Rev 84:869–901Google Scholar
  110. 110.
    Kojima T, Yamamoto T, Murata M, Chiba H, Kokai Y, Sawada N (2003) Med Electron Microsc 36:157–164Google Scholar
  111. 111.
    Simard M, Arcuino G, Takano T, Liu QS, Nedergaard M (2003) J Neurosci 23:9254–9262Google Scholar
  112. 112.
    Brown RC, Davis TP (2002) Stroke 33:1706–1711Google Scholar
  113. 113.
    Vincent PA, Xiao K, Buckley KM, Kowalczyk AP (2004) Am J Physiol Cell Physiol 286:C987–C997Google Scholar
  114. 114.
    Knudsen KA, Soler AP, Johnson KR, Wheelock MJ (1995) J Cell Biol 130:67–77Google Scholar
  115. 115.
    Lampugnani MG, Corada M, Caveda L, Breviario F, Ayalon O, Geiger B, Dejana E (1995) J Cell Biol 129:203–217Google Scholar
  116. 116.
    Watabe-Uchida M, Uchida N, Imamura Y, Nagafuchi A, Fujimoto K, Uemura T, Vermeulen S, van Roy F, Adamson ED, Takeichi M (1998) J Cell Biol 142:847–857Google Scholar
  117. 117.
    Daneman R, Zhou L, Agalliu D, Cahoy JD, Kaushal A, Barres BA (2010) PLoS One 5:e13741Google Scholar
  118. 118.
    Hirase T, Staddon JM, Saitou M, Ando-Akatsuka Y, Itoh M, Furuse M, Fujimoto K, Tsukita S, Rubin LL (1997) J Cell Sci 110:1603–1613Google Scholar
  119. 119.
    Furuse M, Fujita K, Hiiragi T, Fujimoto K, Tsukita S (1998) J Cell Biol 141(7):1539–1550Google Scholar
  120. 120.
    Furuse M, Sasaki H, Tsukita S (1999) J Cell Biol 147:891–903Google Scholar
  121. 121.
    Dejana E, Lampugnani MG, Martinez-Estrada O, Bazzoni G (2000) Int J Dev Biol 44:743–748Google Scholar
  122. 122.
    Martin-Padura I, Lostaglio S, Schneemann M, Williams L, Romano M, Fruscella P, Panzeri C, Stoppacciaro A, Ruco L, Simmons D, Dejana E (1998) J Cell Biol 142:117–127Google Scholar
  123. 123.
    Bauer B, Hartz AM, Fricker G, Miller DS (2004) Mol Pharmacol 66:413–419Google Scholar
  124. 124.
    Bauer H-C, Traweger A, Bauer H (2004) Proteins of the tight junction in the blood–brain barrier. In: Sharma HS, Westman J (eds) Blood-spinal cord and brain barriers in health and disease. Elsevier, San Diego, pp 1–10Google Scholar
  125. 125.
    Xu Z, Waeckerlin R, Urbanowski MD, van Marle G, Hobman TC (2012) PLoS One 7:e37886Google Scholar
  126. 126.
    Del Maschio A, De Luigi A, Martin-Padura I, Brockhaus M, Bartfai T, Fruscella P, Adorini L, Martino GV, Furlan R, De Simoni MG, Dejana E (1999) J Exp Med 190:1351–1356Google Scholar
  127. 127.
    Liebner S, Fischmann A, Rascher G, Duffner F, Grote EH, Kalbacher H, Wolburg H (2000) Acta Neuropathol 100:323–331Google Scholar
  128. 128.
    Hamm S, Dehouck B, Kraus J, Wolburg-Buchholz K, Wolburg H, Risau W, Cecchelli R, Engelhardt B, Dehouck MP (2004) Cell Tissue Res 315:157–166Google Scholar
  129. 129.
    Wolburg H, Wolburg-Buchholz K, Kraus J, Rascher-Eggstein G, Liebner S, Hamm S, Duffner F, Grote EH, Risau W, Engelhardt B (2003) Acta Neuropathol 105:586–592Google Scholar
  130. 130.
    Pfeiffer F, Schäfer J, Lyck R, Makrides V, Brunner S, Schaeren-Wiemers N, Deutsch U, Engelhardt B (2011) Acta Neuropathol 122:601–614Google Scholar
  131. 131.
    Nitta T, Hata M, Gotoh S, Seo Y, Sasaki H, Hashimoto N, Furuse M, Tsukita S (2003) J Cell Biol 161:653–660Google Scholar
  132. 132.
    Bélanger M, Asashima T, Ohtsuki S, Yamaguchi H, Ito S, Terasaki T (2007) Neurochem Int 50:95–101Google Scholar
  133. 133.
    Lai CH et al (2005) Brain Res Brain Res Rev 50:7–13Google Scholar
  134. 134.
    Rosenberg GA (2009) Lancet Neurol 8(2):205–216Google Scholar
  135. 135.
    Jin R, Yang G, Li G (2010) Neurobiol Dis 38:376–385Google Scholar
  136. 136.
    Dahlin A, Royall J, Hohmann JG, Wang J (2009) J Pharmacol Exp Ther 329:558–570Google Scholar
  137. 137.
    Cordon-Cardo C, O'Brien JP, Casals D, Rittman-Grauer L, Biedler JL, Melamed MR, Bertino JR (1989) Proc Natl Acad Sci USA 86:695–698Google Scholar
  138. 138.
    Thiebaut F, Tsuruo T, Hamada H, Gottesman MM, Pastan I, Willingham C et al (1989) J Histochem Cytochem 37:159–164Google Scholar
  139. 139.
    Kania KD, Wijesuriya HC, Hladky SB, Barrand MA (2011) Brain Res 1418:1–11Google Scholar
  140. 140.
    Lim JC, Kania KD, Wijesuriya H, Chawla S, Sethi JK, Pulaski L, Romero IA, Couraud PO, Weksler BB, Hladky SB, Barrand MA (2008) J Neurochem 106:1855–1865Google Scholar
  141. 141.
    Bauer B, Hartz AM, Miller DS (2007) Mol Pharmacol 71:667–675Google Scholar
  142. 142.
    Hartz AM, Bauer B, Fricker G, Miller DS (2006) Mol Pharmacol 69:462–470Google Scholar
  143. 143.
    Hartz AM, Bauer B, Fricker G, Miller DS (2004) Mol Pharmacol 66:387–394Google Scholar
  144. 144.
    Rigor RR, Hawkins BT, Miller DS (2010) J Cereb Blood Flow Metab 30:1373–1383Google Scholar
  145. 145.
    Bankstahl JP, Hoffmann K, Bethmann K, Loscher W (2008) Neuropharmacology 54:1006–1016Google Scholar
  146. 146.
    Bauer B et al (2008) Mol Pharmacol 73:1444–1453Google Scholar
  147. 147.
    Pekcec A et al (2009) J Pharmacol Exp Ther 330:939–947Google Scholar
  148. 148.
    Yousif S, Chaves C, Potin S, Margaill I, Scherrmann JM, Declèves X (2012) J Neurochem 123:491–503Google Scholar
  149. 149.
    Zibell G et al (2009) Neuropharmacology 56:849–855Google Scholar
  150. 150.
    Bauer B et al (2006) Mol Pharmacol 70:1212–1219Google Scholar
  151. 151.
    Dauchy S et al (2008) J Neurochem 107:1518–1528Google Scholar
  152. 152.
    Narang VS et al (2008) Am J Physiol Cell Physiol 295:C440–C450Google Scholar
  153. 153.
    Ott M, Fricker G, Bauer B (2009) J Pharmacol Exp Ther 329:141–149Google Scholar
  154. 154.
    Wang X, Sykes DB, Miller DS (2010) Mol Pharmacol 78:376–383Google Scholar
  155. 155.
    Wang X, Hawkins BT, Miller DS (2011) FASEB J 25:644–652Google Scholar
  156. 156.
    Huber O, Brunner A, Maier P, Kaufmann R, Couraud PO, Cremer C, Fricker G (2012) PLoS One 7:e44776Google Scholar
  157. 157.
    Aronica E, Sisodiya SM, Gorter JA (2012) Adv Drug Deliv Rev 64:919–929Google Scholar
  158. 158.
    Jeynes B, Provias J (2011) Neurosci Lett 487:389–393Google Scholar
  159. 159.
    Potschka H (2012) Adv Drug Deliv Rev 64:943–952Google Scholar
  160. 160.
    van Assema DM, Lubberink M, Bauer M, van der Flier WM, Schuit RC, Windhorst AD, Comans EF, Hoetjes NJ, Tolboom N, Langer O, Müller M, Scheltens P, Lammertsma AA, van Berckel BN (2012) Brain 135:181–189Google Scholar
  161. 161.
    Cooray HC et al (2002) Neuroreport 13:2059–2063Google Scholar
  162. 162.
    Eisenblätter T, Galla HJ (2002) Biochem Biophys Res Commun 293:1273–1278Google Scholar
  163. 163.
    Mahringer A, Fricker G (2010) Mol Pharm 7:1835–1847Google Scholar
  164. 164.
    Dallas S, Miller DS, Bendayan R (2006) Pharmacol Rev 58:140–161Google Scholar
  165. 165.
    Bronger H, Konig J, Kopplow K, Steiner HH, Ahmadi R, Herold-Mende C, Keppler D, Nies AT (2005) Cancer Res 65:11419–11428Google Scholar
  166. 166.
    Leggas M, Adachi M, Scheffer GL, Sun D, Wielinga P, Du G, Mercer KE, Zhuang Y, Panetta JC, Johnston B et al (2004) Mol Cell Biol 24:7612–7621Google Scholar
  167. 167.
    Miller DS, Nobmann SN, Gutmann H, Toeroek M, Drewe J, Fricker G (2000) Mol Pharmacol 58:1357–1367Google Scholar
  168. 168.
    Nies AT, Jedlitschky G, Konig J, Herold-Mende C, Steiner HH, Schmitt HP, Keppler D (2004) Neuroscience 129:349–360Google Scholar
  169. 169.
    Zhang Y, Han H, Elmquist WF, Miller DW (2000) Brain Res 876:148–153Google Scholar
  170. 170.
    Zhang Y, Schuetz JD, Elmquist WF, Miller DW (2004) J Pharmacol Exp Ther 311:449–455Google Scholar
  171. 171.
    Panzenboeck U, Balazs Z, Sovic A, Hrzenjak A, Levak-Frank S, Wintersperger A, Malle E, Sattler W (2002) J Biol Chem 277:42781–42789Google Scholar
  172. 172.
    Shawahna R, Uchida Y, Decleves X, Ohtsuki S, Yousif S, Dauchy S, Jacob A, Chassoux F, Daumas-Duport C, Couraud PO, Terasaki T, Scherrmann JM (2011) Mol Pharm 8:1332–1341Google Scholar
  173. 173.
    Wolf A, Bauer B, Hartz AM (2012) Front Psychiatry 3:54Google Scholar
  174. 174.
    Kusuhara H, Sugiyama Y (2005) NeuroRx 2:73–85Google Scholar
  175. 175.
    Inano A, Sai Y, Nikaido H, Hasimoto N, Asano M, Tsuji A, Tamai I (2003) Drug Dispos 24:357–365Google Scholar
  176. 176.
    Gao B, Stieger B, Noé B, Fritschy JM, Meier PJ (1999) J Histochem Cytochem 47:1255–1264Google Scholar
  177. 177.
    Ohtsuki S, Takizawa T, Takanaga H, Hori S, Hosoya K, Terasaki T (2004) J Neurochem 90:743–749Google Scholar
  178. 178.
    Gao B, Hagenbuch B, Kullak-Ublick GA, Benke D, Aguzzi A, Meier PJ (2000) J Pharmacol Exp Ther 294:73–79Google Scholar
  179. 179.
    Ohtsuki S, Ito S, Matsuda A, Hori S, Abe T, Terasaki T (2007) J Neurochem 103:1430–1438Google Scholar
  180. 180.
    Awasthi S, Hallene KL, Fazio V, Singhal SS, Cuccullo L, Awasthi YC, Dini G, Janigro D (2005) BMC Neurosci 6:61Google Scholar
  181. 181.
    Kalaria RN, Harik SI (1986) J Neurochem 47(6):1849–1856Google Scholar
  182. 182.
    Kook SY, Hong HS, Moon M, Ha CM, Chang S, Mook-Jung I (2012) J Neurosci 32:8845–8854Google Scholar
  183. 183.
    Jones AR, Shusta EV (2007) Pharm Res 24:1759–1771Google Scholar
  184. 184.
    Hervé F, Ghinea N, Scherrmann JM (2008) AAPS J 10:455–472Google Scholar
  185. 185.
    Tuma P, Hubbard AL (2003) Physiol Rev 83:871–932Google Scholar
  186. 186.
    Simionescu M, Ghinea N, Fixman A, Lasser M, Kukes L, Simionescu N, Palade GE (1988) J Submicrosc Cytol Pathol 20:243–261Google Scholar
  187. 187.
    Bickel U, Yoshikawa T, Pardridge WM (2001) Adv Drug Deliv Rev 46:247–279Google Scholar
  188. 188.
    Kumagai AK, Eisenberg JB, Pardridge WM (1987) J Biol Chem 262:15214–15219Google Scholar
  189. 189.
    Dietz GP, Bähr M (2007) Methods Mol Biol 399:181–198Google Scholar
  190. 190.
    Drin G, Mazel M, Clair P, Mathieu D, Kaczorek M, Temsamani J (2001) Eur J Biochem 268:1304–1314Google Scholar
  191. 191.
    Vivès E, Brodin P, Lebleu BJ (1997) Biol Chem 272:16010–16017Google Scholar
  192. 192.
    Wender PA, Mitchell DJ, Pattabiraman K, Pelkey ET, Steinman L, Rothbard JB (2000) Proc Natl Acad Sci USA 97:13003–13008Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Institute of Pharmacy and Molecular BiotechnologyRuprecht-Karls UniversityHeidelbergGermany

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