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Chapter 14 - Imaging Mechanisms of Drug Resistance in Experimental Models of Epilepsy

from Part III - Predicting the Response to Therapeutic Interventions

Published online by Cambridge University Press:  07 January 2019

Andrea Bernasconi
Affiliation:
Montreal Neurological Institute, McGill University
Neda Bernasconi
Affiliation:
Montreal Neurological Institute, McGill University
Matthias Koepp
Affiliation:
Institute of Neurology, University College London
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Publisher: Cambridge University Press
Print publication year: 2019

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References

Brodie, MJ, Barry, SJE, Bamagous, GA, Norrie, JD, Kwan, P. Patterns of treatment response in newly diagnosed epilepsy. Neurology. 2012;78(20):1548–54.Google Scholar
Löscher, W, Klitgaard, H, Twyman, RE, Schmidt, D. New avenues for anti-epileptic drug discovery and development. Nat Rev Drug Discov. 2013;12(10):757–76.Google Scholar
Berg, AT, Berkovic, SF, Brodie, MJ, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005–2009. Epilepsia. 2010;51(4):676–85.Google Scholar
Kwan, P, Arzimanoglou, A, Berg, AT, et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc task force of the ILAE Commission on Therapeutic Strategies. Epilepsia. 2010;51(6):1069–77.Google Scholar
Löscher, W. Critical review of current animal models of seizures and epilepsy used in the discovery and development of new antiepileptic drugs. Seizure. 2011;20(5):359–68.Google Scholar
Potschka, H. Animal models of drug-resistant epilepsy. Epileptic Disord. 2012;14(3):226–34.Google Scholar
Barton, ME, Klein, BD, Wolf, HH, White, HS. Pharmacological characterization of the 6 Hz psychomotor seizure model of partial epilepsy. Epilepsy Res. 2001;47(3):217–27.Google Scholar
Srivastava, AK, White, HS. Carbamazepine, but not valproate, displays pharmacoresistance in lamotrigine-resistant amygdala kindled rats. Epilepsy Res. 2013;104(1–2):2634.Google Scholar
Smyth, MD, Barbaro, NM, Baraban, SC. Effects of antiepileptic drugs on induced epileptiform activity in a rat model of dysplasia. Epilepsy Res. 2002;50(3):251–64.CrossRefGoogle Scholar
Löscher, W. Animal models of drug-refractory epilepsy. In: Pitkänen, A, Schwartzkroin, P, Moshé, S, eds. Models of Seizures and Epilepsy. New York: Academic Press; 2006:551–67.Google Scholar
Löscher, W, Rundfeldt, C. Kindling as a model of drug-resistant partial epilepsy—selection of phenytoin-resistant and nonresistant rats. J Pharmacol Exp Ther. 1991;258(2):483–9.Google Scholar
Bankstahl, M, Bankstahl, JP, Löscher, W. Inter-individual variation in the anticonvulsant effect of phenobarbital in the pilocarpine rat model of temporal lobe epilepsy. Exp Neurol. 2012;234(1):7084.Google Scholar
Brandt, C, Volk, HA, Löscher, W. Striking differences in individual anticonvulsant response to phenobarbital in rats with spontaneous seizures after status epilepticus. Epilepsia. 2004;45(12):1488–97.CrossRefGoogle ScholarPubMed
Glien, M, Brandt, C, Potschka, H, Löscher, W. Effects of the novel antiepileptic drug levetiracetam on spontaneous recurrent seizures in the rat pilocarpine model of temporal lobe epilepsy. Epilepsia. 2002;43(4):350–7.CrossRefGoogle ScholarPubMed
Löscher, W. Mechanisms of drug resistance. Epileptic Disord. 2005;7(suppl 1):39.Google Scholar
Potschka, H, Brodie, MJ. Pharmacoresistance. Handbook Clin Neurol. 2012;108:741–57.Google Scholar
Remy, S, Gabriel, S, Urban, BW, et al. A novel mechanism underlying drug resistance in chronic epilepsy. Ann Neurol. 2003;53(4):469–79.Google Scholar
Remy, S, Urban, BW, Elger, CE, Beck, H. Anticonvulsant pharmacology of voltage-gated Na+ channels in hippocampal neurons of control and chronically epileptic rats. Eur J Neurosci. 2003;17(12):2648–58.CrossRefGoogle ScholarPubMed
Ellerkmann, RK, Remy, S, Chen, J, et al. Molecular and functional changes in voltage-dependent Na+ channels following pilocarpine-induced status epilepticus in rat dentate granule cells. Neuroscience. 2003;119(2):323–33.Google Scholar
Brooks-Kayal, AR, Shumate, MD, Jin, H, Rikhter, TY, Coulter, DA. Selective changes in single cell GABA(A) receptor subunit expression and function in temporal lobe epilepsy. Nat Med. 1998;4(10):1166–72.Google Scholar
Coulter, DA. Mossy fiber zinc and temporal lobe epilepsy: pathological association with altered “epileptic” gamma-aminobutyric acid A receptors in dentate granule cells. Epilepsia. 2000;41:S969.Google Scholar
Volk, HA, Arabadzisz, D, Fritschy, JM, Brandt, C, Bethmann, K, Löscher, W. Antiepileptic drug-resistant rats differ from drug-responsive rats in hippocampal neurodegeneration and GABA(A) receptor ligand binding in a model of temporal lobe epilepsy. Neurobiol Dis. 2006;21(3):633–46.Google Scholar
Löscher, W, Potschka, H. Drug resistance in brain diseases and the role of drug efflux transporters. Nat Rev Neurosci. 2005;6(8):591602.Google Scholar
Zhang, C, Kwan, P, Zuo, Z, Baum, L. The transport of antiepileptic drugs by P-glycoprotein. Adv Drug Deliv Rev. 2012;64(10):930–42.Google Scholar
Kwan, P, Brodie, MJ. Potential role of drug transporters in the pathogenesis of medically intractable epilepsy. Epilepsia. 2005;46(2):224–35.Google Scholar
Potschka, H, Volk, HA, Löscher, W. Pharmacoresistance and expression of multidrug transporter P-glycoprotein in kindled rats. NeuroReport. 2004;15(10):1657–61.Google Scholar
Tishler, DM, Weinberg, KI, Hinton, DR, Barbaro, N, Annett, GM, Raffel, C. Mdr1 gene-expression in brain of patients with medically intractable epilepsy. Epilepsia. 1995;36(1):16.CrossRefGoogle ScholarPubMed
Volk, HA, Löscher, 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;128:1358–68.Google Scholar
Brandt, C, Bethmann, K, Gastens, AM, Löscher, 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(1):202–11.Google Scholar
van Vliet, EA, van Schaik, R, Edelbroek, PM, et al. Inhibition of the multidrug transporter P-glycoprotein improves seizure control in phenytoin-treated chronic epileptic rats. Epilepsia. 2006;47(4):672–80.Google Scholar
Löscher, W, Langer, O. Imaging of P-glycoprotein function and expression to elucidate mechanisms of pharmacoresistance in epilepsy. Curr Top Med Chem. 2010;10(17):1785–91.Google Scholar
Syvänen, S, Eriksson, J. Advances in PET imaging of P-glycoprotein function at the blood-brain barrier. ACS Chem Neurosci. 2013;4(2):225–37.Google Scholar
Bankstahl, JP. What does a picture tell? In vivo imaging of ABC transporter function. Drug Discov Today Technol. 2014;12:e1139.Google Scholar
Hendrikse, NH, Schinkel, AH, De Vries, EGE, et al. Complete in vivo reversal of P-glycoprotein pump function in the blood-brain barrier visualized with positron emission tomography. Br J Pharmacol. 1998;124(7):1413–8.Google Scholar
Luurtsema, G, Molthoff, CFM, Windhorst, AD, et al. (R)- and (S)-[C-11]verapamil as PET-tracers for measuring P-glycoprotein function: in vitro and in vivo evaluation. Nucl Med Biol. 2003;30(7):747–51.Google Scholar
Passchier, J, van Waarde, A, Doze, P, Elsinga, PH, Vaalburg, W. Influence of P-glycoprotein on brain uptake of [18F]MPPF in rats. Eur J Pharmacol. 2000;407(3):273–80.CrossRefGoogle ScholarPubMed
Lazarova, N, Zoghbi, SS, Hong, J, et al. Synthesis and evaluation of [N-methyl-C-11]N-desmethyl-loperamide as a new and improved PET radiotracer for imaging P-gp function. J Med Chem. 2008;51(19):6034–43.Google Scholar
Bankstahl, JP, Kuntner, C, Abrahim, A, et al. Tariquidar-induced P-glycoprotein inhibition at the rat blood-brain barrier studied with (R)-C-11-verapamil and PET. J Nucl Med. 2008;49(8):1328–35.Google Scholar
Farwell, MD, Chong, DJ, Iida, Y, Bae, SA, Easwaramoorthy, B, Ichise, M. Imaging P-glycoprotein function in rats using C-11-N-desmethyl-loperamide. Ann Nucl Med. 2013;27(7):618–24.Google Scholar
Tournier, N, Cisternino, S, Peyronneau, MA, et al. Discrepancies in the P-glycoprotein-mediated transport of F-18-MPPF: a pharmacokinetic study in mice and non-human primates. Pharm Res. 2012;29(9):2468–76.Google Scholar
Mairinger, S, Bankstahl, JP, Kuntner, C, et al. The antiepileptic drug mephobarbital is not transported by P-glycoprotein or multidrug resistance protein 1 at the blood-brain barrier: a positron emission tomography study. Epilepsy Res. 2012;100(1–2):93103.Google Scholar
Verbeek, J, Eriksson, J, Syvanen, S, et al. 11C phenytoin revisited: synthesis by 11C CO carbonylation and first evaluation as a P-gp tracer in rats. EJNMMI Res. 2012;2(1):36.Google Scholar
Sander, K, Galante, E, Gendron, T, et al. Development of fluorine-18 labeled metabolically activated tracers for imaging of drug efflux transporters with positron emission tomography. J Med Chem. 2015;58(15):6058–80.Google Scholar
Bankstahl, JP, Bankstahl, M, Kuntner, C, et al. A novel positron emission tomography imaging protocol identifies seizure-induced regional overactivity of P-glycoprotein at the blood-brain barrier. J Neurosci. 2011;31(24):8803–11.Google Scholar
Kuntner, C, Bankstahl, JP, Bankstahl, M, et al. Dose-response assessment of tariquidar and elacridar and regional quantification of P-glycoprotein inhibition at the rat blood-brain barrier using (R)-[11C]verapamil PET. Eur J Nucl Med Mol Imaging. 2010;37(5):942–53.CrossRefGoogle Scholar
Bauer, M, Zeitlinger, M, Karch, R, et al. Pgp-mediated interaction between (R)-C-11 verapamil and tariquidar at the human blood-brain barrier: a comparison with rat data. Clin Pharmacol Ther. 2012;91(2):227–33.Google Scholar
Feldmann, M, Asselin, MC, Liu, J, et al. P-glycoprotein expression and function in patients with temporal lobe epilepsy: a case-control study. Lancet Neurol. 2013;12(8):777–85.Google Scholar
Moerman, L, Wyffels, L, Slaets, D, Raedt, R, Boon, P, De Vos, F. Antiepileptic drugs modulate P-glycoproteins in the brain: A mice study with 11C-desmethylloperamide. Epilepsy Res. 2011;94(1–2):1825.Google Scholar
Martin, C, Berridge, G, Mistry, P, Higgins, C, Charlton, P, Callaghan, R. The molecular interaction of the high affinity reversal agent XR9576 with P-glycoprotein. Br J Pharmacol. 1999;128(2):403–11.Google Scholar
Bankstahl, JP, Bankstahl, M, Römermann, K, et al. Tariquidar and elacridar are dose-dependently transported by P-glycoprotein and Bcrp at the blood-brain barrier: a small-animal positron emission tomography and in vitro study. Drug Metab Dispos. 2013;41(4):754–62.Google Scholar
Luurtsema, G, Schuit, RC, Klok, RP, et al. Evaluation of C-11 laniquidar as a tracer of P-glycoprotein: radiosynthesis and biodistribution in rats. Nucl Med Biol. 2009;36(6):643–9.Google Scholar
Syvänen, S, Luurtsema, G, Molthoff, C, et al. (R)-[11C]Verapamil PET studies to assess changes in P-glycoprotein expression and functionality in rat blood-brain barrier after exposure to kainate-induced status epilepticus. BMC Med Imaging. 2011;11(1):1.Google Scholar
Bankstahl, JP, Löscher, W. Resistance to antiepileptic drugs and expression of P-glycoprotein in two rat models of status epilepticus. Epilepsy Res. 2008;82(1):7085.Google Scholar
Bartmann, H, Fuest, C, la Fougère, C, et al. Imaging of P-glycoprotein-mediated pharmacoresistance in the hippocampus: Proof-of-concept in a chronic rat model of temporal lobe epilepsy. Epilepsia. 2010;51(9):1780–90.Google Scholar
Syvänen, S, Russmann, V, Verbeek, J, et al. C-11 quinidine and C-11 laniquidar PET imaging in a chronic rodent epilepsy model: Impact of epilepsy and drug-responsiveness. Nucl Med Biol. 2013;40(6):764–75.Google Scholar
Müllauer, J, Karch, R, Bankstahl, JP, et al. Assessment of cerebral P-glycoprotein expression and function with PET by combined [C-11]inhibitor and [C-11]substrate scans in rats. Nucl Med Biol. 2013;40(6):755–63.Google Scholar
Yakushev, IY, Dupont, E, Buchholz, H-G, et al. In vivo imaging of dopamine receptors in a model of temporal lobe epilepsy. Epilepsia. 2010;51(3):415–22.Google Scholar
Goffin, K, Van Paesschen, W, Dupont, P, Van Laere, K. Longitudinal microPET imaging of brain glucose metabolism in rat lithium-pilocarpine model of epilepsy. Exp Neurol. 2009;217(1):205–9.Google Scholar
Guo, Y, Gao, F, Wang, S, et al. In vivo mapping of temporospatial changes in glucose utilization in rat brain during epileptogenesis: an [18F]-fluordeoxyglucose-small animal positron emission tomography study. Neuroscience. 2009;162(4):972–9.CrossRefGoogle ScholarPubMed
Amhaoul, H, Hamaide, J, Bertoglio, D, et al. Brain inflammation in a chronic epilepsy model: Evolving pattern of the translocator protein during epileptogenesis. Neurobiol Dis. 2015;82:526–39.CrossRefGoogle Scholar
Bogdanovic, RM, Syvänen, S, Michler, C, et al. (R)-C-11 PK11195 brain uptake as a biomarker of inflammation and antiepileptic drug resistance: evaluation in a rat epilepsy model. Neuropharmacology. 2014;85:104–12.Google Scholar
Maziere, M, Hantraye, P, Prenant, C, Sastre, J, Comar, D. Synthesis of ethyl 8-fluoro-5,6-dihydro-5-C11 methyl-6-oxo-4h-imidazo 1,5-a 1,4 benzodiazepine-3-carboxylate (RO 15.1788-11C)—a specific radioligand for the in vivo study of central benzodiazepine receptors by positron emission tomography. Int J Appl Radiat Isot. 1984;35(10):973–6.Google Scholar
Froklage, F, Syvanen, S, Hendrikse, NH, et al. [11C]Flumazenil brain uptake is influenced by the blood-brain barrier efflux transporter P-glycoprotein. EJNMMI Res. 2012;2(1):12.Google Scholar
Liefaard, LC, Ploeger, BA, Molthoff, CFM, et al. Changes in GABA(A) receptor properties in amygdala kindled animals: In vivo studies using [C-11]flumazenil and positron emission tomography. Epilepsia. 2009;50(1):8898.CrossRefGoogle ScholarPubMed
Syvänen, S, Labots, M, Tagawa, Y, et al. Altered GABAA receptor density and unaltered blood-brain barrier transport in a kainate model of epilepsy: an in vivo study using 11C-flumazenil and PET. J Nucl Med. 2012;53(12):1974–83.Google Scholar

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