Cerebral expression of drug transporters in epilepsy

Advanced Drug Delivery Reviews

Volumn 64, Issue 10, 2012, Pages 919-929

  Aronica, Eleonora ^a,b   Sisodiya, Sanjay M ^c   Gorter, Jan A ^b,d  

^a UNIVERSITY OF AMSTERDAM   (Netherlands)

^b STICHTING EPILEPSIE INSTELLINGEN NEDERLAND SEIN   (Netherlands)

^c UNIVERSITY COLLEGE LONDON   (United Kingdom)

^d UNIVERSITY OF AMSTERDAM   (Netherlands)

Author keywords

Associated protein; Astrocytes; Blood brain barrier; Brain tumors; Hippocampal sclerosis; Human brain; Malformations of cortical development; Multidrug resistance; Rodent brain

Indexed keywords

ASTROCYTES; BLOOD-BRAIN BARRIER; BRAIN TUMORS; HIPPOCAMPAL SCLEROSIS; HUMAN BRAIN; MALFORMATIONS OF CORTICAL DEVELOPMENT; MULTIDRUG RESISTANCE; RODENT BRAIN;

BLOOD; ENDOTHELIAL CELLS; TISSUE;

BRAIN;

ABC TRANSPORTER; ANTICONVULSIVE AGENT; BREAST CANCER RESISTANCE PROTEIN; CARBAMAZEPINE; CARBAPENEM; CARRIER PROTEIN; DRUG TRANSPORTER; ETIRACETAM; GLYCOPROTEIN P; LAMOTRIGINE; MULTIDRUG RESISTANCE PROTEIN; MULTIDRUG RESISTANCE PROTEIN 1; MULTIDRUG RESISTANCE PROTEIN 2; MULTIDRUG RESISTANCE PROTEIN 3; MULTIDRUG RESISTANCE PROTEIN 4; MULTIDRUG RESISTANCE PROTEIN 5; ORGANIC ANION TRANSPORTER; ORGANIC ANION TRANSPORTER 1; ORGANIC ANION TRANSPORTER 2; ORGANIC ANION TRANSPORTER 3; ORGANIC CATION TRANSPORTER; ORGANIC CATION TRANSPORTER 1; ORGANIC CATION TRANSPORTER 2; ORGANIC CATION TRANSPORTER 3; PHENOBARBITAL; PHENYTOIN; TARIQUIDAR; TOPIRAMATE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VALPROIC ACID;

ASTROCYTE; BLOOD BRAIN BARRIER; BRAIN CELL; CELL TYPE; DRUG BLOOD LEVEL; DRUG TRANSPORT; ENDOTHELIUM CELL; EPILEPSY; EPILEPTIC FOCUS; HUMAN; MICROGLIA; MULTIDRUG RESISTANCE; NERVE CELL; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW;

ANIMALS; BRAIN; EPILEPSY; HUMANS; MEMBRANE TRANSPORT PROTEINS;

EID: 84860745673     PISSN: 0169409X     EISSN: 18728294     Source Type: Journal    
DOI: 10.1016/j.addr.2011.11.008     Document Type: Review

References (197)

1. Lee G., Dallas S., Hong M., Bendayan R. Drug transporters in the central nervous system: brain barriers and brain parenchyma considerations. Pharmacol. Rev. 2001, 53:569-596.
2. Mizuno N., Niwa T., Yotsumoto Y., Sugiyama Y. Impact of drug transporter studies on drug discovery and development. Pharmacol. Rev. 2003, 55:425-461.
3. Girardin F. Membrane transporter proteins: a challenge for CNS drug development. Dialogues Clin. Neurosci. 2006, 8:311-321.
4. Kusuhara H., Sugiyama Y. Active efflux across the blood-brain barrier: role of the solute carrier family. NeuroRx 2005, 2:73-85.
5. Koepsell H. Organic cation transporters in intestine, kidney, liver, and brain. Annu. Rev. Physiol. 1998, 60:243-266.
6. Koepsell H., Lips K., Volk C. Polyspecific organic cation transporters: structure, function, physiological roles, and biopharmaceutical implications. Pharm. Res. 2007, 24:1227-1251.
7. Lin C.J., Tai Y., Huang M.T., Tsai Y.F., Hsu H.J., Tzen K.Y., Liou H.H. Cellular localization of the organic cation transporters, OCT1 and OCT2, in brain microvessel endothelial cells and its implication for MPTP transport across the blood-brain barrier and MPTP-induced dopaminergic toxicity in rodents. J. Neurochem. 2010, 114:717-727.
8. Wu X., Kekuda R., Huang W., Fei Y.J., Leibach F.H., Chen J., Conway S.J., Ganapathy V. Identity of the organic cation transporter OCT3 as the extraneuronal monoamine transporter (uptake2) and evidence for the expression of the transporter in the brain. J. Biol. Chem. 1998, 273:32776-32786.
9. Wu X., Huang W., Prasad P.D., Seth P., Rajan D.P., Leibach F.H., Chen J., Conway S.J., Ganapathy V. Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter. J. Pharmacol. Exp. Ther. 1999, 290:1482-1492.
10. Guo Y., Jiang L. Drug transporters are altered in brain, liver and kidney of rats with chronic epilepsy induced by lithium-pilocarpine. Neurol. Res. 2010, 32:106-112.
11. Higgins C.F. ABC transporters: from microorganisms to man. Annu. Rev. Cell Biol. 1992, 8:67-113.
12. Davidson A.L., Dassa E., Orelle C., Chen J. Structure, function, and evolution of bacterial ATP-binding cassette systems. Microbiol. Mol. Biol. Rev. 2008, 72:317-364. (table of contents).
13. Loscher W., Potschka H. Blood-brain barrier active efflux transporters: ATP-binding cassette gene family. NeuroRx 2005, 2:86-98.
14. Hartz A.M., Bauer B. ABC transporters in the CNS - an inventory. Curr. Pharm. Biotechnol. 2011, 12(4):656-673.
15. Juliano R.L., Ling V. A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim. Biophys. Acta 1976, 455:152-162.
16. Yang K., Wu J., Li X. Recent advances in the research of P-glycoprotein inhibitors. Biosci. Trends 2008, 2:137-146.
17. Cordon-Cardo C., O'Brien J.P., Boccia J., Casals D., Bertino J.R., Melamed M.R. Expression of the multidrug resistance gene product (P-glycoprotein) in human normal and tumor tissues. J. Histochem. Cytochem. 1990, 38:1277-1287.
18. Ernest S., Bello-Reuss E. P-glycoprotein functions and substrates: possible roles of MDR1 gene in the kidney. Kidney Int. Suppl. 1998, 65:S11-S17.
19. Tanigawara Y. Role of P-glycoprotein in drug disposition. Ther. Drug Monit. 2000, 22:137-140.
20. Pendse S., Sayegh M.H., Frank M.H. P-glycoprotein-a novel therapeutic target for immunomodulation in clinical transplantation and autoimmunity?. Curr. Drug Targets 2003, 4:469-476.
21. Meissner K., Sperker B., Karsten C., Meyer Zu Schwabedissen H., Seeland U., Bohm M., Bien S., Dazert P., Kunert-Keil C., Vogelgesang S., Warzok R., Siegmund W., Cascorbi I., Wendt M., Kroemer H.K. Expression and localization of P-glycoprotein in human heart: effects of cardiomyopathy. J. Histochem. Cytochem. 2002, 50:1351-1356.
22. Lazarowski A.J., Garcia Rivello H.J., Vera Janavel G.L., Cuniberti L.A., Cabeza Meckert P.M., Yannarelli G.G., Mele A., Crottogini A.J., Laguens R.P. Cardiomyocytes of chronically ischemic pig hearts express the MDR-1 gene-encoded P-glycoprotein. J. Histochem. Cytochem. 2005, 53:845-850.
23. Luna-Tortos C., Fedrowitz M., Loscher W. Several major antiepileptic drugs are substrates for human P-glycoprotein. Neuropharmacology 2008, 55:1364-1375.
24. Jette L., Tetu B., Beliveau R. High levels of P-glycoprotein detected in isolated brain capillaries. Biochim. Biophys. Acta 1993, 1150:147-154.
25. Schumacher U., Mollgard K. The multidrug-resistance P-glycoprotein (Pgp, MDR1) is an early marker of blood-brain barrier development in the microvessels of the developing human brain. Histochem. Cell Biol. 1997, 108:179-182.
26. Matsuoka Y., Okazaki M., Kitamura Y., Taniguchi T. Developmental expression of P-glycoprotein (multidrug resistance gene product) in the rat brain. J. Neurobiol. 1999, 39:383-392.
27. Dombrowski S.M., Desai S.Y., Marroni M., Cucullo L., Goodrich K., Bingaman W., Mayberg M.R., Bengez L., Janigro D. Overexpression of multiple drug resistance genes in endothelial cells from patients with refractory epilepsy. Epilepsia 2001, 42:1501-1506.
28. Sisodiya S.M., Lin W.R., Harding B.N., Squier M.V., Thom M. Drug resistance in epilepsy: expression of drug resistance proteins in common causes of refractory epilepsy. Brain 2002, 125:22-31.
29. Aronica E., Gorter J.A., Ramkema M., Redeker S., Ozbas-Gercerer F., Van Vliet E.A., Scheffer G.L., Scheper R.J., Van Der Valk P., Baayen J.C., Troost D. Expression and cellular distribution of multidrug resistance-related proteins in the hippocampus of patients with mesial temporal lobe epilepsy. Epilepsia 2004, 45:441-451.
30. van Vliet E., Aronica E., Redeker S., Marchi N., Rizzi M., Vezzani A., Gorter J. Selective and persistent upregulation of mdr1b mRNA and P-glycoprotein in the parahippocampal cortex of chronic epileptic rats. Epilepsy Res. 2004, 60:203-213.
31. Soontornmalai A., Vlaming M.L., Fritschy J.M. Differential, strain-specific cellular and subcellular distribution of multidrug transporters in murine choroid plexus and blood-brain barrier. Neuroscience 2006, 138:159-169.
32. Sisodiya S.M., Martinian L., Scheffer G.L., van der Valk P., Scheper R.J., Harding B.N., Thom M. Vascular colocalization of P-glycoprotein, multidrug-resistance associated protein 1, breast cancer resistance protein and major vault protein in human epileptogenic pathologies. Neuropathol. Appl. Neurobiol. 2006, 32:51-63.
33. van Vliet E.A., Zibell G., Pekcec A., Schlichtiger J., Edelbroek P.M., Holtman L., Aronica E., Gorter J.A., Potschka H. COX-2 inhibition controls P-glycoprotein expression and promotes brain delivery of phenytoin in chronic epileptic rats. Neuropharmacology 2010, 58:404-412.
34. van Kalken C.K., Giaccone G., van der Valk P., Kuiper C.M., Hadisaputro M.M., Bosma S.A., Scheper R.J., Meijer C.J., Pinedo H.M. Multidrug resistance gene (P-glycoprotein) expression in the human fetus. Am. J. Pathol. 1992, 141:1063-1072.
35. Schumacher U., Mollgard K. The multidrug-resistance P-glycoprotein (Pgp, MDR1) is an early marker of blood-brain barrier development in the microvessels of the developing human brain. Histochem. Cell Biol. 1997, 108:179-182.
36. Virgintino D., Errede M., Girolamo F., Capobianco C., Robertson D., Vimercati A., Serio G., Di Benedetto A., Yonekawa Y., Frei K., Roncali L. Fetal blood-brain barrier P-glycoprotein contributes to brain protection during human development. J. Neuropathol. Exp. Neurol. 2008, 67:50-61.
37. Daood M., Tsai C., Ahdab-Barmada M., Watchko J.F. ABC transporter (P-gp/ABCB1, MRP1/ABCC1, BCRP/ABCG2) expression in the developing human CNS. Neuropediatrics 2008, 39:211-218.
38. Bendayan R., Lee G., Bendayan M. Functional expression and localization of P-glycoprotein at the blood brain barrier. Microsc. Res. Tech. 2002, 57:365-380.
39. Golden P.L., Pardridge W.M. P-Glycoprotein on astrocyte foot processes of unfixed isolated human brain capillaries. Brain Res. 1999, 819:143-146.
40. Schlachetzki F., Pardridge W.M. P-glycoprotein and caveolin-1alpha in endothelium and astrocytes of primate brain. Neuroreport 2003, 14:2041-2046.
41. Volk H., Potschka H., Loscher W. Immunohistochemical localization of P-glycoprotein in rat brain and detection of its increased expression by seizures are sensitive to fixation and staining variables. J. Histochem. Cytochem. 2005, 53:517-531.
42. Decleves X., Regina A., Laplanche J.L., Roux F., Boval B., Launay J.M., Scherrmann J.M. Functional expression of P-glycoprotein and multidrug resistance-associated protein (Mrp1) in primary cultures of rat astrocytes. J. Neurosci. Res. 2000, 60:594-601.
43. M. Marroni, M. Agarwal, K. Kight, K.L. Hallene, M. Hissein, L. Cucullo, K. Signorelli, S. Namura, D. Janigro, (in press). Relathionship between expression of multiple drug resistance proteins and p53 tumor suppressor gene proteins in human brain astrocytes, Neuroscience 121 (3) (2003) 605-617.
44. Lee G., Schlichter L., Bendayan M., Bendayan R. Functional expression of P-glycoprotein in rat brain microglia. J. Pharmacol. Exp. Ther. 2001, 299:204-212.
45. Manzini I., Schild D. Multidrug resistance transporters in the olfactory receptor neurons of Xenopus laevis tadpoles. J. Physiol. 2003, 546:375-385.
46. Pallis M., Turzanski J., Higashi Y., Russell N. P-glycoprotein in acute myeloid leukaemia: therapeutic implications of its association with both a multidrug-resistant and an apoptosis-resistant phenotype. Leuk. Lymphoma 2002, 43:1221-1228.
47. Kooij G., Backer R., Koning J.J., Reijerkerk A., van Horssen J., van der Pol S.M., Drexhage J., Schinkel A., Dijkstra C.D., den Haan J.M., Geijtenbeek T.B., de Vries H.E. P-glycoprotein acts as an immunomodulator during neuroinflammation. PLoS One 2009, 4:e8212.
48. Kooij G., Mizee M.R., van Horssen J., Reijerkerk A., Witte M.E., Drexhage J.A., van der Pol S.M., van Het Hof B., Scheffer G., Scheper R., Dijkstra C.D., van der Valk P., de Vries H.E. Adenosine triphosphate-binding cassette transporters mediate chemokine (C-C motif) ligand 2 secretion from reactive astrocytes: relevance to multiple sclerosis pathogenesis. Brain 2011, 134:555-570.
49. Shapiro A.B., Ling V. The mechanism of ATP-dependent multidrug transport by P-glycoprotein. Acta Physiol. Scand. Suppl. 1998, 643:227-234.
50. Rajagopal A., Simon S.M. Subcellular localization and activity of multidrug resistance proteins. Mol. Biol. Cell 2003, 14:3389-3399.
51. Sun H., Dai H., Shaik N., Elmquist W.F. Drug efflux transporters in the CNS. Adv. Drug Deliv. Rev. 2003, 55(1):83-105.
52. Marquez B., Van Bambeke F. ABC multidrug transporters: target for modulation of drug pharmacokinetics and drug-drug interactions. Curr. Drug Targets 2011, 12(5):600-620.
53. Schinkel A.H., Jonker J.W. Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview. Adv. Drug Deliv. Rev. 2003, 55:3-29.
54. Kubota H., Ishihara H., Langmann T., Schmitz G., Stieger B., Wieser H.G., Yonekawa Y., Frei K. Distribution and functional activity of P-glycoprotein and multidrug resistance-associated proteins in human brain microvascular endothelial cells in hippocampal sclerosis. Epilepsy Res. 2006, 68:213-228.
55. Warren M.S., Zerangue N., Woodford K., Roberts L.M., Tate E.H., Feng B., Li C., Feuerstein T.J., Gibbs J., Smith B., de Morais S.M., Dower W.J., Koller K.J. Comparative gene expression profiles of ABC transporters in brain microvessel endothelial cells and brain in five species including human. Pharmacol. Res. 2009, 59:404-413.
56. van Vliet E.A., Redeker S., Aronica E., Edelbroek P.M., Gorter J.A. Expression of multidrug transporters MRP1, MRP2, and BCRP shortly after status epilepticus, during the latent period, and in chronic epileptic rats. Epilepsia 2005, 46:1569-1580.
57. Aronica E., Gorter J.A., Jansen G.H., van Veelen C.W., van Rijen P.C., Leenstra S., Ramkema M., Scheffer G.L., Scheper R.J., Troost D. Expression and cellular distribution of multidrug transporter proteins in two major causes of medically intractable epilepsy: focal cortical dysplasia and glioneuronal tumors. Neuroscience 2003, 118:417-429.
58. Aronica E., Gorter J.A., Ramkema M., Redeker S., Ozbas-Gerceker F., van Vliet E.A., Scheffer G.L., Scheper R.J., van der Valk P., Baayen J.C., Troost D. Expression and cellular distribution of multidrug resistance-related proteins in the hippocampus of patients with mesial temporal lobe epilepsy. Epilepsia 2004, 45:441-451.
59. Nies A.T., Jedlitschky G., Konig J., Herold-Mende C., Steiner H.H., Schmitt H.P., Keppler D. Expression and immunolocalization of the multidrug resistance proteins, MRP1-MRP6 (ABCC1-ABCC6), in human brain. Neuroscience 2004, 129:349-360.
60. Rao V.V., Dahlheimer J.L., Bardgett M.E., Snyder A.Z., Finch R.A., Sartorelli A.C., Piwnica-Worms D. Choroid plexus epithelial expression of MDR1 P glycoprotein and multidrug resistance-associated protein contribute to the blood-cerebrospinal-fluid drug-permeability barrier. Proc. Natl. Acad. Sci. U. S. A. 1999, 96:3900-3905.
61. Hirrlinger J., Konig J., Dringen R. Expression of mRNAs of multidrug resistance proteins (Mrps) in cultured rat astrocytes, oligodendrocytes, microglial cells and neurones. J. Neurochem. 2002, 82:716-719.
62. Harris H.E., Raucci A. Alarmin(g) news about danger: workshop on innate danger signals and HMGB1. EMBO Rep. 2006, 7:774-778.
63. Bianchi M.E. HMGB1 loves company. J. Leukoc. Biol. 2009, 86:573-576.
64. Litman T., Druley T.E., Stein W.D., Bates S.E. From MDR to MXR: new understanding of multidrug resistance systems, their properties and clinical significance. Cell. Mol. Life Sci. 2001, 58:931-959.
65. Lage H., Dietel M. Effect of the breast-cancer resistance protein on atypical multidrug resistance. Lancet Oncol. 2000, 1:169-175.
66. Doyle L.A., Ross D.D. Multidrug resistance mediated by the breast cancer resistance protein BCRP (ABCG2). Oncogene 2003, 22:7340-7358.
67. Bates S.E., Robey R., Miyake K., Rao K., Ross D.D., Litman T. The role of half-transporters in multidrug resistance. J. Bioenerg. Biomembr. 2001, 33:503-511.
68. Maliepaard M., Scheffer G.L., Faneyte I.F., van Gastelen M.A., Pijnenborg A.C., Schinkel A.H., van De Vijver M.J., Scheper R.J., Schellens J.H. Subcellular localization and distribution of the breast cancer resistance protein transporter in normal human tissues. Cancer Res. 2001, 61:3458-3464.
69. Cooray H.C., Blackmore C.G., Maskell L., Barrand M.A. Localisation of breast cancer resistance protein in microvessel endothelium of human brain. Neuroreport 2002, 13:2059-2063.
70. Eisenblatter T., Huwel S., Galla H.J. Characterisation of the brain multidrug resistance protein (BMDP/ABCG2/BCRP) expressed at the blood-brain barrier. Brain Res. 2003, 971:221-231.
71. Aronica E., Gorter J.A., Redeker S., van Vliet E.A., Ramkema M., Scheffer G.L., Scheper R.J., van der Valk P., Leenstra S., Baayen J.C., Spliet W.G., Troost D. Localization of breast cancer resistance protein (BCRP) in microvessel endothelium of human control and epileptic brain. Epilepsia 2005, 46:849-857.
72. Polgar O., Robey R.W., Bates S.E. ABCG2: structure, function and role in drug response. Expert Opin. Drug Metab. Toxicol. 2008, 4:1-15.
73. Cerveny L., Pavek P., Malakova J., Staud F., Fendrich Z. Lack of interactions between breast cancer resistance protein (bcrp/abcg2) and selected antiepileptic agents. Epilepsia 2006, 47:461-468.
74. Awasthi Y.C., Chaudhary P., Vatsyayan R., Sharma A., Awasthi S., Sharma R. Physiological and pharmacological significance of glutathione-conjugate transport. J. Toxicol. Environ. Health B Crit. Rev. 2009, 12:540-551.
75. Singhal S.S., Yadav S., Roth C., Singhal J. RLIP76: a novel glutathione-conjugate and multi-drug transporter. Biochem. Pharmacol. 2009, 77:761-769.
76. Awasthi S., Hallene K.L., Fazio V., Singhal S.S., Cucullo L., Awasthi Y.C., Dini G., Janigro D. RLIP76, a non-ABC transporter, and drug resistance in epilepsy. BMC Neurosci. 2005, 6:61.
77. Soranzo N., Kelly L., Martinian L., Burley M.W., Thom M., Sali A., Kroetz D.L., Goldstein D.B., Sisodiya S.M. Lack of support for a role for RLIP76 (RALBP1) in response to treatment or predisposition to epilepsy. Epilepsia 2007, 48:674-683.
78. Janigro D., Awasthi S., Awasthi Y.C., Sharma R., Yadav S., Singhal S.S., Hallene K. RLIP76 in AED drug resistance. Epilepsia 2007, 48:1218-1219. (author reply 1219-1220).
79. Kwan P., Brodie M.J. Potential role of drug transporters in the pathogenesis of medically intractable epilepsy. Epilepsia 2005, 46:224-235.
80. Loscher W., Potschka H. Drug resistance in brain diseases and the role of drug efflux transporters. Nat. Rev. Neurosci. 2005, 6:591-602.
81. Loscher W. Drug transporters in the epileptic brain. Epilepsia 2007, 48(Suppl. 1):8-13.
82. Marchi N., Gonzalez-Martinez J., Nguyen M.T., Granata T., Janigro D. Transporters in drug-refractory epilepsy: clinical significance. Clin. Pharmacol. Ther. 2010, 87:13-15.
83. Sillanpaa M., Schmidt D. Natural history of treated childhood-onset epilepsy: prospective, long-term population-based study. Brain 2006, 129:617-624.
84. Hitiris N., Mohanraj R., Norrie J., Sills G.J., Brodie M.J. Predictors of pharmacoresistant epilepsy. Epilepsy Res. 2007, 75:192-196.
85. French J.A. Refractory epilepsy: clinical overview. Epilepsia 2007, 48(Suppl. 1):3-7.
86. Rogawski M.A., Johnson M.R. Intrinsic severity as a determinant of antiepileptic drug refractoriness. Epilepsy Curr. 2008, 8:127-130.
87. Schmidt D., Loscher W. New developments in antiepileptic drug resistance: an integrative view. Epilepsy Curr. 2009, 9:47-52.
88. Picot M.C., Baldy-Moulinier M., Daures J.P., Dujols P., Crespel A. The prevalence of epilepsy and pharmacoresistant epilepsy in adults: a population-based study in a Western European country. Epilepsia 2008, 49:1230-1238.
89. van Breemen M.S., Wilms E.B., Vecht C.J. Epilepsy in patients with brain tumours: epidemiology, mechanisms, and management. Lancet Neurol. 2007, 6:421-430.
90. Wieser H.G. I.C.o.N.o. epilepsy, ILAE commission report. Mesial temporal lobe epilepsy with hippocampal sclerosis. Epilepsia 2004, 45:695-714.
91. Thom M. Hippocampal sclerosis: progress since Sommer. Brain Pathol. 2009, 19:565-572.
92. Tishler D.M., Weinberg K.I., Hinton D.R., Barbaro N., Annett G.M., Raffel C. MDR1 gene expression in brain of patients with medically intractable epilepsy. Epilepsia 1995, 36:1-6.
93. Chengyun D., Guoming L., Elia M., Catania M.V., Qunyuan X. Expression of multidrug resistance type 1 gene (MDR1) P-glycoprotein in intractable epilepsy with different aetiologies: a double-labelling and electron microscopy study. Neurol. Sci. 2006, 27:245-251.
94. Marchi N., Guiso G., Rizzi M., Pirker S., Novak K., Czech T., Baumgartner C., Janigro D., Caccia S., Vezzani A. A pilot study on brain-to-plasma partition of 10,11-dyhydro-10-hydroxy-5H-dibenzo(b,f)azepine-5-carboxamide and MDR1 brain expression in epilepsy patients not responding to oxcarbazepine. Epilepsia 2005, 46:1613-1619.
95. Cucullo L., Hossain M., Rapp E., Manders T., Marchi N., Janigro D. Development of a humanized in vitro blood-brain barrier model to screen for brain penetration of antiepileptic drugs. Epilepsia 2007, 48:505-516.
96. Renes J., de Vries E.E., Hooiveld G.J., Krikken I., Jansen P.L., Muller M. Multidrug resistance protein MRP1 protects against the toxicity of the major lipid peroxidation product 4-hydroxynonenal. Biochem. J. 2000, 350(Pt. 2):555-561.
97. Renes J., de Vries E.G., Jansen P.L., Muller M. The (patho)physiological functions of the MRP family. Drug Resist. Updat. 2000, 3:289-302.
98. 11C]verapamil. Epilepsia 2007, 48:1774-1784.
99. 11C-verapamil and PET. J. Nucl. Med. 2008, 49:1328-1335.
100. 11C]verapamil PET. Eur. J. Nucl. Med. Mol. Imaging 2010, 37:942-953.
101. Bauer M., Karch R., Neumann F., Wagner C.C., Kletter K., Muller M., Loscher W., Zeitlinger M., Langer O. Assessment of regional differences in tariquidar-induced P-glycoprotein modulation at the human blood-brain barrier. J. Cereb. Blood Flow Metab. 2010, 30:510-515.
102. Blumcke I. Neuropathology of focal epilepsies: a critical review. Epilepsy Behav. 2009, 15:34-39.
103. Blümcke I., Vinters H.V., Armstrong D., Aronica E., Thom M., Spreafico R. Malformations of cortical development and epilepsies: neuropathological findings with emphasis on focal cortical dysplasia. Epileptic Disord. 2009, 11:181-193.
104. Sisodiya S.M., Heffernan J., Squier M.V. Over-expression of P-glycoprotein in malformations of cortical development. Neuroreport 1999, 10:3437-3441.
105. Lazarowski A., Sevlever G., Taratuto A., Massaro M., Rabinowicz A. Tuberous sclerosis associated with MDR1 gene expression and drug-resistant epilepsy. Pediatr. Neurol. 1999, 21:731-734.
106. Sisodiya S.M., Lin W.R., Squier M.V., Thom M. Multidrug-resistance protein 1 in focal cortical dysplasia. Lancet 2001, 357:42-43.
107. Lazarowski A., Lubieniecki F., Camarero S., Pomata H., Bartuluchi M., Sevlever G., Taratuto A.L. Multidrug resistance proteins in tuberous sclerosis and refractory epilepsy. Pediatr. Neurol. 2004, 30:102-106.
108. Lazarowski A.J., Lubieniecki F.J., Camarero S.A., Pomata H.H., Bartuluchi M.A., Sevlever G., Taratuto A.L. New proteins configure a brain drug resistance map in tuberous sclerosis. Pediatr. Neurol. 2006, 34:20-24.
109. Boer K., Troost D., Jansen F., Nellist M., van den Ouweland A.M., Geurts J.J., Spliet W.G., Crino P., Aronica E. Clinicopathological and immunohistochemical findings in an autopsy case of tuberous sclerosis complex. Neuropathology 2008, 28:577-590.
110. Iyer A., Zurolo E., Spliet W.G.M., van Rijen P.C., Baayen J.C., Gorter J.A., Aronica E. Evaluation of the innate and adaptive immunity in type I and type II focal cortical dysplasias. Epilepsia 2010, 51(9):1763-1773.
111. Bleau A.M., Hambardzumyan D., Ozawa T., Fomchenko E.I., Huse J.T., Brennan C.W., Holland E.C. PTEN/PI3K/Akt pathway regulates the side population phenotype and ABCG2 activity in glioma tumor stem-like cells. Cell Stem Cell 2009, 4:226-235.
112. McCubrey J.A., Steelman L.S., Kempf C.R., Chappell W., Abrams S.L., Stivala F., Malaponte G., Nicoletti F., Libra M., Basecke J., Maksimovic-Ivanic D., Mijatovic S., Montalto G., Cervello M., Cocco L., Martelli A.M. Therapeutic resistance resulting from mutations in Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR signaling pathways. J. Cell. Physiol. 2011, 226(11):2762-2781.
113. Decleves X., Amiel A., Delattre J.Y., Scherrmann J.M. Role of ABC transporters in the chemoresistance of human gliomas. Curr. Cancer Drug Targets 2006, 6:433-445.
114. Lu C., Shervington A. Chemoresistance in gliomas. Mol. Cell. Biochem. 2008, 312:71-80.
115. Bleau A.M., Huse J.T., Holland E.C. The ABCG2 resistance network of glioblastoma. Cell Cycle 2009, 8:2936-2944.
116. Dean M. ABC transporters, drug resistance, and cancer stem cells. J. Mammary Gland Biol. Neoplasia 2009, 14:3-9.
117. Rizzi M., Caccia S., Guiso G., Richichi C., Gorter J.A., Aronica E., Aliprandi M., Bagnati R., Fanelli R., D'Incalci M., Samanin R., Vezzani A. Limbic seizures induce P-glycoprotein in rodent brain: functional implications for pharmacoresistance. J. Neurosci. 2002, 22:5833-5839.
118. Potschka H., Volk H.A., Loscher W. Pharmacoresistance and expression of multidrug transporter P-glycoprotein in kindled rats. Neuroreport 2004, 15:1657-1661.
119. Volk H.A., Burkhardt K., Potschka H., Chen J., Becker A., Loscher W. Neuronal expression of the drug efflux transporter P-glycoprotein in the rat hippocampus after limbic seizures. Neuroscience 2004, 123:751-759.
120. Volk H.A., Potschka H., Loscher W. Increased expression of the multidrug transporter P-glycoprotein in limbic brain regions after amygdala-kindled seizures in rats. Epilepsy Res. 2004, 58:67-79.
121. Volk H.A., Loscher W. Multidrug resistance in epilepsy: rats with drug-resistant seizures exhibit enhanced brain expression of P-glycoprotein compared with rats with drug-responsive seizures. Brain 2005, 128:1358-1368.
122. Pekcec A., Unkruer B., Stein V., Bankstahl J.P., Soerensen J., Tipold A., Baumgartner W., Potschka H. Over-expression of P-glycoprotein in the canine brain following spontaneous status epilepticus. Epilepsy Res. 2009, 83:144-151.
123. Marchi N., Guiso G., Caccia S., Rizzi M., Gagliardi B., Noe F., Ravizza T., Bassanini S., Chimenti S., Battaglia G., Vezzani A. Determinants of drug brain uptake in a rat model of seizure-associated malformations of cortical development. Neurobiol. Dis. 2006, 24:429-442.
124. Hoffmann K., Gastens A.M., Volk H.A., Loscher W. Expression of the multidrug transporter MRP2 in the blood-brain barrier after pilocarpine-induced seizures in rats. Epilepsy Res. 2006, 69:1-14.
125. Loscher W., Brandt C. High seizure frequency prior to antiepileptic treatment is a predictor of pharmacoresistant epilepsy in a rat model of temporal lobe epilepsy. Epilepsia 2010, 51:89-97.
126. Luna-Tortos C., Fedrowitz M., Loscher W. Evaluation of transport of common antiepileptic drugs by human multidrug resistance-associated proteins (MRP1, 2 and 5) that are overexpressed in pharmacoresistant epilepsy. Neuropharmacology 2010, 58:1019-1032.
127. Loscher W., Luna-Tortos C., Romermann K., Fedrowitz M. Do ABC transporters cause pharmacoresistance in epilepsy? Problems and approaches in determining which antiepileptic drugs are affected. Curr. Pharm. Des. 2011, 17(26):2808-2828.
128. Zhang C., Kwan P., Zuo Z., Baum L. In vitro concentration dependent transport of phenytoin and phenobarbital, but not ethosuximide, by human P-glycoprotein. Life Sci. 2010, 86:899-905.
129. Zhang C., Zuo Z., Kwan P., Baum L. In vitro transport profile of carbamazepine, oxcarbazepine, eslicarbazepine acetate, and their active metabolites by human P-glycoprotein. Epilepsia 2011, 52(10):1894-1904.
130. Hocht C., Lazarowski A., Gonzalez N.N., Auzmendi J., Opezzo J.A., Bramuglia G.F., Taira C.A., Girardi E. Nimodipine restores the altered hippocampal phenytoin pharmacokinetics in a refractory epileptic model. Neurosci. Lett. 2007, 413:168-172.
131. Hocht C., Lazarowski A., Gonzalez N.N., Mayer M.A., Opezzo J.A., Taira C.A., Girardi E. Differential hippocampal pharmacokinetics of phenobarbital and carbamazepine in repetitive seizures induced by 3-mercaptopropionic acid. Neurosci. Lett. 2009, 453:54-57.
132. van Vliet E.A., van Schaik R., Edelbroek P.M., Voskuyl R.A., Redeker S., Aronica E., Wadman W.J., Gorter J.A. Region-specific overexpression of P-glycoprotein at the blood-brain barrier affects brain uptake of phenytoin in epileptic rats. J. Pharmacol. Exp. Ther. 2007, 322:141-147.
133. Brandt C., Bethmann K., Gastens A.M., Loscher W. The multidrug transporter hypothesis of drug resistance in epilepsy: proof-of-principle in a rat model of temporal lobe epilepsy. Neurobiol. Dis. 2006, 24:202-211.
134. van Vliet E.A., van Schaik R., Edelbroek P.M., Redeker S., Aronica E., Wadman W.J., Marchi N., Vezzani A., Gorter J.A. Inhibition of the multidrug transporter P-glycoprotein improves seizure control in phenytoin-treated chronic epileptic rats. Epilepsia 2006, 47:672-680.
135. Bartmann H., Fuest C., la Fougere C., Xiong G., Just T., Schlichtiger J., Winter P., Boning G., Wangler B., Pekcec A., Soerensen J., Bartenstein P., Cumming P., Potschka H. Imaging of P-glycoprotein-mediated pharmacoresistance in the hippocampus: proof-of-concept in a chronic rat model of temporal lobe epilepsy. Epilepsia 2010, 51:1780-1790.
136. Miller D.S., Bauer B., Hartz A.M. Modulation of P-glycoprotein at the blood-brain barrier: opportunities to improve central nervous system pharmacotherapy. Pharmacol. Rev. 2008, 60:196-209.
137. Potschka H. Targeting regulation of ABC efflux transporters in brain diseases: a novel therapeutic approach. Pharmacol. Ther. 2010, 125:118-127.
138. Siddiqui A., Kerb R., Weale M.E., Brinkmann U., Smith A., Goldstein D.B., Wood N.W., Sisodiya S.M. Association of multidrug resistance in epilepsy with a polymorphism in the drug-transporter gene ABCB1. N. Engl. J. Med. 2003, 348:1442-1448.
139. Tan N.C., Heron S.E., Scheffer I.E., Pelekanos J.T., McMahon J.M., Vears D.F., Mulley J.C., Berkovic S.F. Failure to confirm association of a polymorphism in ABCB1 with multidrug-resistant epilepsy. Neurology 2004, 63:1090-1092.
140. Sills G.J., Mohanraj R., Butler E., McCrindle S., Collier L., Wilson E.A., Brodie M.J. Lack of association between the C3435T polymorphism in the human multidrug resistance (MDR1) gene and response to antiepileptic drug treatment. Epilepsia 2005, 46:643-647.
141. Basic S., Hajnsek S., Poljakovic Z., Basic M. Lack of association between the C3435T polymorphism in the human multidrug resistance (MDR1) gene and response to antiepileptic drug treatment. Epilepsia 2006, 47:449. (author reply 450).
142. Kim D.W., Lee S.K., Chu K., Jang I.J., Yu K.S., Cho J.Y., Kim S.J. Lack of association between ABCB1, ABCG2, and ABCC2 genetic polymorphisms and multidrug resistance in partial epilepsy. Epilepsy Res. 2009, 84:86-90.
143. Sisodiya S.M., Marini C. Genetics of antiepileptic drug resistance. Curr. Opin. Neurol. 2009, 22:150-156.
144. Ufer M., Mosyagin I., Muhle H., Jacobsen T., Haenisch S., Hasler R., Faltraco F., Remmler C., von Spiczak S., Kroemer H.K., Runge U., Boor R., Stephani U., Cascorbi I. Non-response to antiepileptic pharmacotherapy is associated with the ABCC2-24C>T polymorphism in young and adult patients with epilepsy. Pharmacogenet. Genomics 2009, 19:353-362.
145. Aronica E., Gorter J.A., Jansen G.H., van Veelen C.W.M., van Rijen P.C., Leenstra S., Ramkema M., Scheffer G.L., Scheper R.J., Troost D. Expression and cellular distribution of multidrug transporter proteins in two major causes of medically intractable epilepsy: focal cortical dysplasia and glioneuronal tumors. Neuroscience 2003, 118:417-429.
146. Schick V., Majores M., Koch A., Elger C.E., Schramm J., Urbach H., Becker A.J. Alterations of phosphatidylinositol 3-kinase pathway components in epilepsy-associated glioneuronal lesions. Epilepsia 2007, 48(Suppl. 5):65-73.
147. Boer K., Troost D., Timmerman W., Spliet W.G.M., van Rijen P.C., Aronica E. Pi3K-mTOR signaling and AMOG expression in epilepsy-associated glioneuronal tumors. Brain Pathol. 2010, 20(1):234-244.
148. Orlova K.A., Tsai V., Baybis M., Heuer G.G., Sisodiya S., Thom M., Strauss K., Aronica E., Storm P.B., Crino P.B. Early progenitor cell marker expression distinguishes type II from type I focal cortical dysplasias. J. Neuropathol. Exp. Neurol. 2010, 69:850-863.
149. Yu A. Role of microRNAs in the regulation of drug metabolism and disposition. Expert Opin. Drug Metab. Toxicol. 2009, 5:1513-1528.
150. Ma J., Dong C., Ji C. MicroRNA and drug resistance. Cancer Gene Ther. 2010, 17:523-531.
151. Cao X., Yeo G., Muotri A.R., Kuwabara T., Gage F.H. Noncoding RNAs in the mammalian central nervous system. Annu. Rev. Neurosci. 2006, 29:77-103.
152. Tsai L.M., Yu D. MicroRNAs in common diseases and potential therapeutic applications. Clin. Exp. Pharmacol. Physiol. 2010, 37:102-107.
153. Zhu H., Wu H., Liu X., Evans B.R., Medina D.J., Liu C.G., Yang J.M. Role of MicroRNA miR-27a and miR-451 in the regulation of MDR1/P-glycoprotein expression in human cancer cells. Biochem. Pharmacol. 2008, 76:582-588.
154. Pan Y.Z., Morris M.E., Yu A.M. MicroRNA-328 negatively regulates the expression of breast cancer resistance protein (BCRP/ABCG2) in human cancer cells. Mol. Pharmacol. 2009, 75:1374-1379.
155. Li Z., Hu S., Wang J., Cai J., Xiao L., Yu L., Wang Z. MiR-27a modulates MDR1/P-glycoprotein expression by targeting HIPK2 in human ovarian cancer cells. Gynecol. Oncol. 2010, 119:125-130.
156. Aronica E., Gorter J.A., Van Vliet E.A., Spliet W.G., Van Veelen C.W., Van Rijen P.C., Leenstra S., Ramkema M.D., Scheffer G.L., Scheper R.J., Sisodiya S.M., Troost D. Overexpression of the human major vault protein in gangliogliomas. Epilepsia 2003, 44:1166-1175.
157. Rizzi M., Caccia S., Guiso G., Richichi C., Gorter J.A., Aronica E., Aliprandi M., Bagnati R., Fanelli R., D'Incalci M., Samanin R., Vezzani A. Limbic seizures induce P-glycoprotein in rodent brain: functional implications for pharmacoresistance. J. Neurosci. 2002, 22:5833-5839.
158. Yang L., Yong Y., Xuefeng W. Antiepileptic drug-induced multidrug resistance P-glycoprotein overexpression in astrocytes cultured from rat brains. Chin. Med. J. 2004, 117:1682-1686.
159. Yang H.W., Liu H.Y., Liu X., Zhang D.M., Liu Y.C., Liu X.D., Wang G.J., Xie L. Increased P-glycoprotein function and level after long-term exposure of four antiepileptic drugs to rat brain microvascular endothelial cells in vitro. Neurosci. Lett. 2008, 434:299-303.
160. Ambroziak K., Kuteykin-Teplyakov K., Luna-Tortos C., Al-Falah M., Fedrowitz M., Loscher W. Exposure to antiepileptic drugs does not alter the functionality of P-glycoprotein in brain capillary endothelial and kidney cell lines. Eur. J. Pharmacol. 2010, 628:57-66.
161. Wen T., Liu Y.C., Yang H.W., Liu H.Y., Liu X.D., Wang G.J., Xie L. Effect of 21-day exposure of phenobarbital, carbamazepine and phenytoin on P-glycoprotein expression and activity in the rat brain. J. Neurol. Sci. 2008, 270:99-106.
162. 11C-desmethylloperamide. Epilepsy Res. 2011, 94:18-25.
163. Bauer B., Hartz A.M., Pekcec A., Toellner K., Miller D.S., Potschka H. Seizure-induced up-regulation of P-glycoprotein at the blood-brain barrier through glutamate and cyclooxygenase-2 signaling. Mol. Pharmacol. 2008, 73:1444-1453.
164. Pekcec A., Unkruer B., Schlichtiger J., Soerensen J., Hartz A.M., Bauer B., van Vliet E.A., Gorter J.A., Potschka H. Targeting prostaglandin E2 EP1 receptors prevents seizure-associated P-glycoprotein up-regulation. J. Pharmacol. Exp. Ther. 2009, 330:939-947.
165. Vezzani A., French J., Bartfai T., Baram T.Z. The role of inflammation in epilepsy. Nat. Rev. Neurol. 2010, (online publication 7 December 2010). 10.1038/nrneurol.2010.178.
166. Stein U., Walther W. Cytokine-mediated reversal of multidrug resistance. Cytotechnology 1998, 27:271-282.
167. Kuteykin-Teplyakov K., Brandt C., Hoffmann K., Loscher W. Complex time-dependent alterations in the brain expression of different drug efflux transporter genes after status epilepticus. Epilepsia 2009, 50:887-897.
168. Goralski K.B., Hartmann G., Piquette-Miller M., Renton K.W. Downregulation of mdr1a expression in the brain and liver during CNS inflammation alters the in vivo disposition of digoxin. Br. J. Pharmacol. 2003, 139:35-48.
169. Theron D., Barraud de Lagerie S., Tardivel S., Pelerin H., Demeuse P., Mercier C., Mabondzo A., Farinotti R., Lacour B., Roux F., Gimenez F. Influence of tumor necrosis factor-alpha on the expression and function of P-glycoprotein in an immortalised rat brain capillary endothelial cell line, GPNT. Biochem. Pharmacol. 2003, 66:579-587.
170. Hartz A.M., Bauer B., Fricker G., Miller D.S. Rapid regulation of P-glycoprotein at the blood-brain barrier by endothelin-1. Mol. Pharmacol. 2004, 66:387-394.
171. Hartz A.M., Bauer B., Fricker G., Miller D.S. Rapid modulation of P-glycoprotein-mediated transport at the blood-brain barrier by tumor necrosis factor-alpha and lipopolysaccharide. Mol. Pharmacol. 2006, 69:462-470.
172. Bauer B., Hartz A.M., Miller D.S. Tumor necrosis factor alpha and endothelin-1 increase P-glycoprotein expression and transport activity at the blood-brain barrier. Mol. Pharmacol. 2007, 71:667-675.
173. von Wedel-Parlow M., Wolte P., Galla H.J. Regulation of major efflux transporters under inflammatory conditions at the blood-brain barrier in vitro. J. Neurochem. 2009, 111:111-118.
174. Monville C., Fages C., Feyens A.M., D'Hondt V., Guillet C., Vernallis A., Gascan H., Peschanski M. Astroglial expression of the P-glycoprotein is controlled by intracellular CNTF. BMC Cell Biol. 2002, 3:20.
175. Ronaldson P.T., Bendayan R. HIV-1 viral envelope glycoprotein gp120 triggers an inflammatory response in cultured rat astrocytes and regulates the functional expression of P-glycoprotein. Mol. Pharmacol. 2006, 70:1087-1098.
176. Ronaldson P.T., Ashraf T., Bendayan R. Regulation of multidrug resistance protein 1 by tumor necrosis factor alpha in cultured glial cells: involvement of nuclear factor-kappaB and c-Jun N-terminal kinase signaling pathways. Mol. Pharmacol. 2010, 77:644-659.
177. Gorter J.A., van Vliet E.A., Aronica E., Breit T., Rauwerda H., Lopes da Silva F.H., Wadman W.J. Potential new antiepileptogenic targets indicated by microarray analysis in a rat model for temporal lobe epilepsy. J. Neurosci. 2006, 26:11083-11110.
178. Wu Y., Wang X., Mo X., Xi Z., Xiao F., Li J., Zhu X., Luan G., Wang Y., Li Y., Zhang J. Expression of monocyte chemoattractant protein-1 in brain tissue of patients with intractable epilepsy. Clin. Neuropathol. 2008, 27:55-63.
179. Boer K., Crino P.B., Gorter J.A., Nellist M., Jansen F.E., Spliet W.G., van Rijen P.C., Wittink F.R., Breit T.M., Troost D., Wadman W.J., Aronica E. Gene expression analysis of tuberous sclerosis complex cortical tubers reveals increased expression of adhesion and inflammatory factors. Brain Pathol. 2010, 20:704-719.
180. Iyer A., Zurolo E., Spliet W.G., van Rijen P.C., Baayen J.C., Gorter J.A., Aronica E. Evaluation of the innate and adaptive immunity in type I and type II focal cortical dysplasias. Epilepsia 2010, 51:1763-1773.
181. Ito K., Suzuki H., Horie T., Sugiyama Y. Apical/basolateral surface expression of drug transporters and its role in vectorial drug transport. Pharm. Res. 2005, 22:1559-1577.
182. Takano M., Yumoto R., Murakami T. Expression and function of efflux drug transporters in the intestine. Pharmacol. Ther. 2006, 109:137-161.
183. Lazarowski A., Czornyj L., Lubienieki F., Girardi E., Vazquez S., D'Giano C. ABC transporters during epilepsy and mechanisms underlying multidrug resistance in refractory epilepsy. Epilepsia 2007, 48(Suppl. 5):140-149.
184. Lazarowski A., Czornyj L. Potential role of multidrug resistant proteins in refractory epilepsy and antiepileptic drugs interactions. Drug Metabol. Drug Interact. 2011, 26:21-26.
185. Kock K., Grube M., Jedlitschky G., Oevermann L., Siegmund W., Ritter C.A., Kroemer H.K. Expression of adenosine triphosphate-binding cassette (ABC) drug transporters in peripheral blood cells: relevance for physiology and pharmacotherapy. Clin. Pharmacokinet. 2007, 46:449-470.
186. Mancl E.E., Gidal B.E. The effect of carbapenem antibiotics on plasma concentrations of valproic acid. Ann. Pharmacother. 2009, 43:2082-2087.
187. Coves-Orts F.J., Borras-Blasco J., Navarro-Ruiz A., Murcia-Lopez A., Palacios-Ortega F. Acute seizures due to a probable interaction between valproic acid and meropenem. Ann. Pharmacother. 2005, 39:533-537.
188. Fudio S., Carcas A., Pinana E., Ortega R. Epileptic seizures caused by low valproic acid levels from an interaction with meropenem. J. Clin. Pharm. Ther. 2006, 31:393-396.
189. Lazarowski A., Massaro M., Schteinschnaider A., Intruvini S., Sevlever G., Rabinowicz A. Neuronal MDR-1 gene expression and persistent low levels of anticonvulsants in a child with refractory epilepsy. Ther. Drug Monit. 2004, 26:44-46.
190. Marchi N., Betto G., Fazio V., Fan Q., Ghosh C., Machado A., Janigro D. Blood-brain barrier damage and brain penetration of antiepileptic drugs: role of serum proteins and brain edema. Epilepsia 2009, 50:664-677.
191. Marchi N., Hallene K.L., Kight K.M., Cucullo L., Moddel G., Bingaman W., Dini G., Vezzani A., Janigro D. Significance of MDR1 and multiple drug resistance in refractory human epileptic brain. BMC Med. 2004, 2:37.
192. Liu X., Yang Z., Yang J., Yang H. Increased P-glycoprotein expression and decreased phenobarbital distribution in the brain of pentylenetetrazole-kindled rats. Neuropharmacology 2007, 53:657-663.
193. Pekcec A., Unkruer B., Schlichtiger J., Soerensen J., Hartz A.M., Bauer B., van Vliet E.A., Gorter J.A., Potschka H. Targeting prostaglandin E2 EP1 receptors prevents seizure-associated P-glycoprotein up-regulation. J. Pharmacol. Exp. Ther. 2009, 330:939-947.
194. Zhang L., Ong W.Y., Lee T. Induction of P-glycoprotein expression in astrocytes following intracerebroventricular kainate injections. Exp. Brain Res. 1999, 126:509-516.
195. Seegers U., Potschka H., Loscher W. Transient increase of P-glycoprotein expression in endothelium and parenchyma of limbic brain regions in the kainate model of temporal lobe epilepsy. Epilepsy Res. 2002, 51:257-268.
196. van Vliet E.A., da Costa Araujo S., Redeker S., van Schaik R., Aronica E., Gorter J.A. Blood-brain barrier leakage may lead to progression of temporal lobe epilepsy. Brain 2007, 130:521-534.
197. Fabene P.F., Navarro Mora G., Martinello M., Rossi B., Merigo F., Ottoboni L., Bach S., Angiari S., Benati D., Chakir A., Zanetti L., Schio F., Osculati A., Marzola P., Nicolato E., Homeister J.W., Xia L., Lowe J.B., McEver R.P., Osculati F., Sbarbati A., Butcher E.C., Constantin G. A role for leukocyte-endothelial adhesion mechanisms in epilepsy. Nat. Med. 2008, 14:1377-1383. (see comment).