Advertisement

Role of Adenosine Receptors in Epileptic Seizures

  • Diogo Miguel Rombo
  • Joaquim Alexandre Ribeiro
  • Ana Maria Sebastião
Chapter
Part of the The Receptors book series (REC, volume 34)

Abstract

Epileptic seizures are caused by an electrical disturbance of brain activity that results in abnormal and excessive synchronization of neurons. Adenosine is a long-known anticonvulsant endogenous substance, exerting its actions through diverse mechanisms of action at different cellular targets. In this review we discuss the main actions of adenosine during acute and chronic phases of epileptic seizure progression and the mechanisms involved. There should be considered three main levels of adenosine actions: (1) neuronal level, where adenosine, mostly through its receptors A1, A2A and A3, alters intrinsic neuronal properties and excitatory/inhibitory network balance; (2) non-neuronal level, by affecting astrocytic function; and (3) homeostatic control level, through epigenetic regulatory mechanisms. Together, these actions make adenosine as a sort of “universal modulator or maestro” of desynchronization of epileptic focus, with great therapeutic potential in the treatment of resistant forms of epileptic seizures. Indeed, adenosine augmentation therapies are being considered to tackle epilepsy, which include gene therapy strategies and dietary interventions. Further research on new drugs that specifically target the mechanisms of actions involved in the pathological process of the disease are needed to take full advantage of adenosine anticonvulsant actions in the control of epileptic seizures.

Keywords

Epilepsy Seizure models Neuroprotection Adenosine-control mechanisms Adenosine-based therapies GABAergic transmission. 

Notes

Acknowledgements

The research carried out by the authors of this work have been supported by LISBOA-01-0145-FEDER-007391, project co-funded by FEDER through POR Lisboa 2020 (Programa Operacional Regional de Lisboa) from PORTUGAL 2020 and Fundação para a Ciência e Tecnologia (FCT), by an FCT project (PTDC/DTP-FTO/3346/2014) and by Twinning action (SynaNet) from the EU H2020 programme (project number: 692340).

References

  1. Adami M, Bertorelli R, Ferri N et al (1995) Effects of repeated administration of selective adenosine A1 and A2A receptor agonists on pentylenetetrazole-induced convulsions in the rat. Eur J Pharmacol 294:383–389. https://doi.org/10.1016/0014-2999(95)00557-9CrossRefPubMedGoogle Scholar
  2. Adén U, O’Connor WT, Berman RF (2004) Changes in purine levels and adenosine receptors in kindled seizures in the rat. Neuroreport 15:1585–1589. https://doi.org/10.1097/01.wnr.0000133227CrossRefPubMedGoogle Scholar
  3. Akula KK, Kulkarni SK (2014) Effect of Curcumin Against Pentylenetetrazol- Induced Seizure Threshold in Mice : Possible Involvement of Adenosine A 1 Receptors. Phytother Res 721:714–721CrossRefGoogle Scholar
  4. Alasvand Zarasvand M, Mirnajafi-Zadeh J, Fathollahi Y, Palizvan MR (2001) Anticonvulsant effect of bilateral injection of N6-cyclohexyladenosine into the CA1 region of the hippocampus in amygdala-kindled rats. Epilepsy Res 47:141–149. https://doi.org/10.1016/S0920-1211(01)00300-XCrossRefPubMedGoogle Scholar
  5. Albertson TE, Stark LG, Joy RM, Bowyer JF (1983) Aminophylline and kindled seizures. Exp Neurol 81:703–713CrossRefPubMedGoogle Scholar
  6. Alzheimer C, Sutor B, ten Bruggencate G (1989) Transient and selective blockade of adenosine A1-receptors by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) causes sustained epileptiform activity in hippocampal CA3 neurons of guinea pigs. Neurosci Lett 99:107–112. https://doi.org/10.1016/0304-3940(89)90273-90275CrossRefPubMedGoogle Scholar
  7. Alzheimer C, Sutor B, Ten Bruggencate G (1993) Disinhibition of hippocampal CA3 neurons induced by suppression of an adenosine A1 receptor-mediated inhibitory tonus: Pre- and postsynaptic components. Neuroscience 57:565–575. https://doi.org/10.1016/0306-4522(93)90006-2CrossRefPubMedGoogle Scholar
  8. Angelatou F, Pagonopoulou O, Kostopoulos G (1990) Alterations of A1 adenosine receptors in different mouse brain areas after pentylenetetrazol-induced seizures, but not in the epileptic mutant mouse “tottering”. Brain Res 534:251–256. https://doi.org/10.1016/0006-8993(90)90136-YCrossRefPubMedGoogle Scholar
  9. Angelatou F, Pagonopoulou O, Kostopoulos G (1991) Changes in seizure latency correlate with alterations in A1 adenosine receptor binding during daily repeated pentylenetetrazol-induced convulsions in different mouse brain areas. Neurosci Lett 132:203–206. https://doi.org/10.1016/0304-3940(91)90302-ACrossRefPubMedGoogle Scholar
  10. Angelatou F, Pagonopoulou O, Maraziotis T et al (1993) Upregulation of A1 adenosine receptors in human temporal lobe epilepsy: a quantitative autoradiographic study. NeurosciLett 163:11–14Google Scholar
  11. Aronica E, Zurolo E, Iyer A et al (2011) Upregulation of adenosine kinase in astrocytes in experimental and human temporal lobe epilepsy. Epilepsia 52:1645–1655. https://doi.org/10.1111/j.1528-1167.2011.03115.xCrossRefPubMedPubMedCentralGoogle Scholar
  12. Arvidsson SB, Ekström-Jodal B, Martinell SA, Niemand D (1982) Aminophylline antagonises diazepam sedation. Lancet (London, England) 2:1467CrossRefGoogle Scholar
  13. Arvin B, Neville LF, Pan J, Roberts PJ (1989) 2-chloroadenosine attenuates kainic acid-induced toxicity within the rat straitum: relationship to release of glutamate and Ca2+ influx. Br J Pharmacol 98:225–235CrossRefPubMedPubMedCentralGoogle Scholar
  14. Avsar E, Empson RM (2004) Adenosine acting via A1 receptors, controls the transition to status epilepticus-like behaviour in an in vitro model of epilepsy. Neuropharmacology 47:427–437. https://doi.org/10.1016/j.neuropharm.2004.04.015CrossRefPubMedGoogle Scholar
  15. Banerjee PN, Filippi D, Allen Hauser W (2009) The descriptive epidemiology of epilepsy-A review. Epilepsy Res 85:31–45. https://doi.org/10.1016/j.eplepsyres.2009.03.003CrossRefPubMedPubMedCentralGoogle Scholar
  16. Barraco RA, Swanson TH, Phillis JW, Berman RF (1984) Anticonvulsant effects of adenosine analogues on amygdaloid- kindled seizures in rats. Neurosci Lett 46:317–322CrossRefPubMedGoogle Scholar
  17. Beghi E, Hesdorffer D (2014) Prevalence of epilepsy-An unknown quantity. Epilepsia 55:963–967. https://doi.org/10.1111/epi.12579CrossRefPubMedGoogle Scholar
  18. Bell GS, Neligan A, Sander JW (2014) An unknown quantity - The worldwide prevalence of epilepsy. Epilepsia 55:958–962. https://doi.org/10.1111/epi.12605CrossRefPubMedGoogle Scholar
  19. Bender AS, Hertz L (1986) Similarities of adenosine uptake systems in astrocytes and neurons in primary cultures. Neurochem Res 11:1507–1524CrossRefPubMedGoogle Scholar
  20. Berg AT, Millichap JJ (2013) The 2010 revised classification of seizures and epilepsy. Continuum (Minneap Minn) 19:571–597. https://doi.org/10.1212/01.CON.0000431377.44312.9eCrossRefGoogle Scholar
  21. Berman RF, Fredholm BB, Aden U, Connor WTO (2000) Evidence for increased dorsal hippocampal adenosine release and metabolism during pharmacologically induced seizures in rats. Brain Res 872:44–53CrossRefPubMedGoogle Scholar
  22. Bialer M, White HS (2010) Key factors in the discovery and development of new antiepileptic drugs. Nat Rev Drug Discov 9:68–82. https://doi.org/10.1038/nrd2997CrossRefPubMedGoogle Scholar
  23. Bjursell MK, Blom HJ, Cayuela JA et al (2011) Adenosine kinase deficiency disrupts the methionine cycle and causes hypermethioninemia, encephalopathy, and abnormal liver function. Am J Hum Genet 89:507–515. https://doi.org/10.1016/j.ajhg.2011.09.004CrossRefPubMedPubMedCentralGoogle Scholar
  24. Boison D (2006) Adenosine kinase, epilepsy and stroke: mechanisms and therapies. Trends Pharmacol Sci 27:652–658. https://doi.org/10.1016/j.tips.2006.10.008CrossRefPubMedGoogle Scholar
  25. Boison D (2008) The adenosine kinase hypothesis of epileptogenesis. Prog Neurobiol 84:249–262. https://doi.org/10.1016/j.pneurobio.2007.12.002CrossRefPubMedGoogle Scholar
  26. Boison D (2010) Inhibitory RNA in epilepsy: Research tools and therapeutic perspectives. Epilepsia 51:1659–1668. https://doi.org/10.1111/j.1528-1167.2010.02672.xCrossRefPubMedPubMedCentralGoogle Scholar
  27. Boison D (2016a) Adenosinergic signaling in epilepsy. Neuropharmacology 104:131–139. https://doi.org/10.1016/j.neuropharm.2015.08.046CrossRefPubMedGoogle Scholar
  28. Boison D (2016b) The Biochemistry and Epigenetics of Epilepsy: Focus on Adenosine and Glycine. Front Mol Neurosci 9:26. https://doi.org/10.3389/fnmol.2016.00026CrossRefPubMedPubMedCentralGoogle Scholar
  29. Boison D, Scheurer L, Tseng JL et al (1999) Seizure suppression in kindled rats by intraventricular grafting of an adenosine releasing synthetic polymer. Exp Neurol 160:164–174. https://doi.org/10.1006/exnr.1999.7209CrossRefPubMedGoogle Scholar
  30. Boison D, Huber A, Padrun V et al (2002) Seizure suppression by adenosine-releasing cells is independent of seizure frequency. Epilepsia 43:788–796. https://doi.org/10.1046/j.1528-1157.2002.33001.xCrossRefPubMedGoogle Scholar
  31. Bonan CD, Amaral OB, Rockenbach IC et al (2000a) Altered ATP hydrolysis induced by pentylenetetrazol kindling in rat brain synaptosomes. Neurochem Res 25:775–779. https://doi.org/10.1023/A:1007557205523CrossRefPubMedGoogle Scholar
  32. Bonan CD, Walz R, Pereira GS et al (2000b) Changes in synaptosomal ectonucleotidase activities in two rat models of temporal lobe epilepsy. Epilepsy Res 39:229–238. https://doi.org/10.1016/S0920-1211(00)00095-4CrossRefPubMedGoogle Scholar
  33. Borowicz KK, Kleinrok Z, Czuczwar SJ (1997) N6-2-(4-aminophenyl) ethyl-adenosine enhances the anticonvulsive activity of antiepileptic drug. Eur J Pharmacol 327:125–133. https://doi.org/10.1016/S0014-2999(97)89651-3CrossRefPubMedGoogle Scholar
  34. Borowicz KK, Kleinrok Z, Czuczwar SJ (2000) N6-2-(4-Aminophenyl)ethyl-adenosine enhances the anticonvulsive action of conventional antiepileptic drugs in the kindling model of epilepsy in rats. Eur Neuropsychopharmacol 10:237–243. https://doi.org/10.1016/S0924-977X(00)00081-XCrossRefPubMedGoogle Scholar
  35. Borowicz KK, Luszczki J, Czuczwar SJ (2002) 2-Chloroadenosine, a preferential agonist of adenosine A1 receptors, enhances the anticonvulsant activity of carbamazepine and clonazepam in mice. Eur Neuropsychopharmacol 12:173–179. https://doi.org/10.1016/S0924-977X(02)00009-3CrossRefPubMedGoogle Scholar
  36. Borowicz KK, Swiader M, Wielosz M, Czuczwar SJ (2004) Influence of the combined treatment of LY 300164 (an AMPA/kainate receptor antagonist) with adenosine receptor agonists on the electroconvulsive threshold in mice. Eur Neuropsychopharmacol 14:407–412. https://doi.org/10.1016/j.euroneuro.2003.12.003CrossRefPubMedGoogle Scholar
  37. Bough KJ, Rho JM (2007) Anticonvulsant mechanisms of the ketogenic diet. Epilepsia 48:43–58. https://doi.org/10.1111/j.1528-1167.2007.00915.xCrossRefPubMedGoogle Scholar
  38. Bouilleret V, Ridoux V, Depaulis A et al (1999) Recurrent seizures and hippocampal sclerosis following intrahippocampal kainate injection in adult mice: Electroencephalography, histopathology and synaptic reorganization similar to mesial temporal lobe epilepsy. Neuroscience 89:717–729. https://doi.org/10.1016/S0306-4522(98)00401-1CrossRefPubMedGoogle Scholar
  39. Brodie MS, Lee K, Fredholm BB et al (1987) Central versus peripheral mediation of responses to adenosine receptor agonists: Evidence against a central mode of action. Brain Res 415:323–330. https://doi.org/10.1016/0006-8993(87)90214-9CrossRefPubMedGoogle Scholar
  40. Chen J-F, Pedata F (2008) Modulation of ischemic brain injury and neuroinflammation by adenosine A2A receptors. Curr Pharm Des 14:1490–1499CrossRefPubMedGoogle Scholar
  41. Chen Z, Xiong C, Pancyr C et al (2014) Prolonged Adenosine A1 Receptor Activation in Hypoxia and Pial Vessel Disruption Focal Cortical Ischemia Facilitates Clathrin-Mediated AMPA Receptor Endocytosis and Long-Lasting Synaptic Inhibition in Rat Hippocampal CA3-CA1 Synapses: Differential Regulat. J Neurosci 34:9621–9643. https://doi.org/10.1523/JNEUROSCI.3991-13.2014CrossRefPubMedGoogle Scholar
  42. Chin JH (1989) Adenosine receptors in brain: neuromodulation and role in epilepsy. Ann Neurol 26:695–698. https://doi.org/10.1002/ana.410260602CrossRefPubMedGoogle Scholar
  43. Clark BD, Kurth-Nelson ZL, Newman EA (2009) Adenosine-evoked hyperpolarization of retinal ganglion cells is mediated by G-protein-coupled inwardly rectifying K+ and small conductance Ca2+-activated K+ channel activation. J Neurosci 29:11237–11245. https://doi.org/10.1523/JNEUROSCI.2836-09.2009CrossRefPubMedPubMedCentralGoogle Scholar
  44. Concas A, Santoro G, Mascia MP et al (1993) Anticonvulsant doses of 2-chloro-N6-cyclopentyladenosine, an adenosine A1 receptor agonist, reduce GABAergic transmission in different areas of the mouse brain. J Pharmacol Exp Ther 267:844–851PubMedGoogle Scholar
  45. Cristóvão-Ferreira S, Vaz SH, Ribeiro JA, Sebastião AM (2009) Adenosine A2A receptors enhance GABA transport into nerve terminals by restraining PKC inhibition of GAT-1. J Neurochem 109:336–347. https://doi.org/10.1111/j.1471-4159.2009.05963.xCrossRefPubMedGoogle Scholar
  46. Cristóvão-Ferreira S, Navarro G, Brugarolas M et al (2013) A1R-A2AR heteromers coupled to Gs and G i/0 proteins modulate GABA transport into astrocytes. Purinergic Signal 9:433–449. https://doi.org/10.1007/s11302-013-9364-5CrossRefPubMedPubMedCentralGoogle Scholar
  47. Cunha RA (2001) Adenosine as a neuromodulator and as a homeostatic regulator in the nervous system: different roles, different sources and different receptors. Neurochem Int 38:107–125CrossRefPubMedGoogle Scholar
  48. Cunha RA (2005) Neuroprotection by adenosine in the brain: From A(1) receptor activation to A (2A) receptor blockade. Purinergic Signal 1:111–134. https://doi.org/10.1007/s11302-005-0649-1CrossRefPubMedPubMedCentralGoogle Scholar
  49. Cunha RA, Correia-de-Sá P, Sebastião AM, Ribeiro JA (1996) Preferential activation of excitatory adenosine receptors at rat hippocampal and neuromuscular synapses by adenosine formed from released adenine nucleotides. Br J Pharmacol 119:253–260CrossRefPubMedPubMedCentralGoogle Scholar
  50. Czuczwar SJ, Turski WA, Ikonomidou C, Turski L (1985) Aminophylline and CGS 8216 Reverse the Protective Action of Diazepam Against Electroconvulsions in Mice. Epilepsia 26:693–696. https://doi.org/10.1111/j.1528-1157.1985.tb05713.xCrossRefPubMedGoogle Scholar
  51. Czuczwar SJ, Szczepanik B, Wamil A et al (1990) Differential effects of agents enhancing purinergic transmission upon the antielectroshock efficacy of carbamazepine, diphenylhydantoin, diazepam, phenobarbital, and valproate in mice. J Neural Transm 81:153–166. https://doi.org/10.1007/BF01245835CrossRefGoogle Scholar
  52. D’Alimonte I, D’Auro M, Citraro R et al (2009) Altered distribution and function of A2A adenosine receptors in the brain of WAG/Rij rats with genetic absence epilepsy, before and after appearance of the disease. Eur J Neurosci 30:1023–1035. https://doi.org/10.1111/j.1460-9568.2009.06897.xCrossRefPubMedGoogle Scholar
  53. Dai S-S, Zhou Y-G (2011) Adenosine 2A receptor: a crucial neuromodulator with bidirectional effect in neuroinflammation and brain injury. Rev Neurosci 22:231–239. https://doi.org/10.1515/RNS.2011.020CrossRefPubMedGoogle Scholar
  54. Daval JL, Sarfati A (1987) Effects of bicuculline-induced seizures on benzodiazepine and adenosine receptors in developing rat brain. Life Sci 41:1685–1693. https://doi.org/10.1016/0024-3205(87)90595-9CrossRefPubMedGoogle Scholar
  55. Daval J, Werck M (1991) Autoradiographic changes in brain adenosine A1 receptors and their coupling to G proteins following seizures in the developing rat. Brain Res Dev Brain Res 59:237–247CrossRefPubMedGoogle Scholar
  56. Davies LP (1985) Pharmacological studies on adenosine analogues isolated from marine organisms. Trends Pharmacol Sci 6:143–146. https://doi.org/10.1016/0165-6147(85)90066-5CrossRefGoogle Scholar
  57. de Groot M, Iyer A, Zurolo E et al (2012) Overexpression of ADK in human astrocytic tumors and peritumoral tissue is related to tumor-associated epilepsy. Epilepsia 53:58–66. https://doi.org/10.1111/j.1528-1167.2011.03306.xCrossRefPubMedGoogle Scholar
  58. De Mendonça A, Ribeiro JA (2000) Long-term potentiation observed upon blockade of adenosine A1 receptors in rat hippocampus is N-methyl-D-aspartate receptor-dependent. Neurosci Lett 291:81–84. https://doi.org/10.1016/S0304-3940(00)01391-4CrossRefPubMedGoogle Scholar
  59. De Mendonça A, Sebastião AM, Ribeiro JA (1995) Inhibition of NMDA receptor-mediated currents in isolated rat hippocampal neurones by adenosine A1 receptor activation. Neuroreport 6:1097–1100CrossRefPubMedGoogle Scholar
  60. De Sarro G, De Sarro A, Donato E et al (1999) Effects of adenosine receptor agonists and antagonists on audiogenic seizure-sensible DBAr2 mice. Eur J Pharmacol 371:137–145CrossRefPubMedGoogle Scholar
  61. Dias RB, Ribeiro JA, Sebastião AM (2012) Enhancement of AMPA currents and GluR1 membrane expression through PKA-coupled adenosine A(2A) receptors. Hippocampus 22:276–291. https://doi.org/10.1002/hipo.20894CrossRefPubMedGoogle Scholar
  62. Dias RB, Rombo DM, Ribeiro JA, Sebastião AM (2013) Ischemia-induced synaptic plasticity drives sustained expression of calcium-permeable AMPA receptors in the hippocampus. Neuropharmacology 65:114–122. https://doi.org/10.1016/j.neuropharm.2012.09.016CrossRefPubMedGoogle Scholar
  63. Dodd PR, Watson WE, Johnston GA (1986) Adenosine receptors in post-mortem human cerebral cortex and the effect of carbamazepine. Clin Exp Pharmacol Physiol 13:711–722CrossRefPubMedGoogle Scholar
  64. Dragunow M, Goddard GV (1984) Adenosine modulation of amygdala kindling. Exp Neurol 84:654–665. https://doi.org/10.1016/0014-4886(84)90212-7CrossRefPubMedGoogle Scholar
  65. Dragunow M, Robertson HA (1987) 8-Cyclopentyl 1,3-dimethylxanthine prolongs epileptic seizures in rats. Brain Res 417:377–379. https://doi.org/10.1016/0006-8993(87)90468-9CrossRefPubMedGoogle Scholar
  66. Dragunow M, Goddard GV, Laverty R (1985) Is adenosine an endogenous anticonvulsant? Epilepsia 26:480–487CrossRefPubMedGoogle Scholar
  67. Dunwiddie TV (1980) Endogenously released adenosine regulates excitability in the in vitro hippocampus. Epilepsia 21:541–548. https://doi.org/10.1111/j.1528-1157.1980.tb04305.xCrossRefPubMedGoogle Scholar
  68. Dunwiddie TV, Hoffer BJ (1980) Adenine nucleotides and synaptic transmission in the in vitro rat hippocampus. Br J Pharmacol 69:59–68CrossRefPubMedPubMedCentralGoogle Scholar
  69. Dunwiddie TV, Worth T (1982) Sedative and anticonvulsant effects of adenosine analogs in mouse and rat. J Pharmacol Exp Ther 220:70–76PubMedGoogle Scholar
  70. Dunwiddie TV, Diao L, Kim HO et al (1997) Activation of hippocampal adenosine A3 receptors produces a desensitization of A1 receptor-mediated responses in rat hippocampus. J Neurosci 17:607–614CrossRefPubMedPubMedCentralGoogle Scholar
  71. During MJ, Spencer DD (1992) Adenosine: A potential mediator of seizure arrest and postictal refractoriness. Ann Neurol 32:618–624. https://doi.org/10.1002/ana.410320504CrossRefPubMedGoogle Scholar
  72. Ehrengruber MU, Doupnik CA, Xu Y et al (1997) Activation of heteromeric G protein-gated inward rectifier K+ channels overexpressed by adenovirus gene transfer inhibits the excitability of hippocampal neurons. Proc Natl Acad Sci U S A 94:7070–7075CrossRefPubMedPubMedCentralGoogle Scholar
  73. Ekonomou A, Vergnes M, Kostopoulos G (1998) Lower density of A1 adenosine receptors in nucleus reticularis thalami in rats with genetic absence epilepsy. Neuroreport 9:2135–2140CrossRefPubMedGoogle Scholar
  74. Ekonomou A, Sperk G, Kostopoulos G, Angelatou F (2000) Reduction of A1 adenosine receptors in rat hippocampus after kainic acid-induced limbic seizures. NeurosciLett 284:49–52Google Scholar
  75. El Yacoubi M, Ledent C, Parmentier M et al (2001) Absence of the adenosine A2A receptor or its chronic blockade decrease ethanol withdrawal-induced seizures in mice. Neuropharmacology 40:424–432. https://doi.org/10.1016/S0028-3908(00)00173-8CrossRefPubMedGoogle Scholar
  76. El Yacoubi M, Ledent C, Parmentier M et al (2008) Evidence for the involvement of the adenosine A2A receptor in the lowered susceptibility to pentylenetetrazol-induced seizures produced in mice by long-term treatment with caffeine. Neuropharmacology 55:35–40. https://doi.org/10.1016/j.neuropharm.2008.04.007CrossRefPubMedGoogle Scholar
  77. El Yacoubi M, Ledent C, Parmentier M et al (2009) Adenosine A2A receptor deficient mice are partially resistant to limbic seizures. Naunyn Schmiedebergs Arch Pharmacol 380:223–232. https://doi.org/10.1007/s00210-009-0426-8CrossRefPubMedGoogle Scholar
  78. Eldridge FL, Paydarfar D, Scott SC, Dowell RT (1989) Role of endogenous adenosine in recurrent generalized seizures. Exp Neurol 103:179–185. https://doi.org/10.1016/0014-4886(89)90080-0CrossRefPubMedGoogle Scholar
  79. Engel J (1996a) Surgery for Seizures. N Engl J Med 334:647–653. https://doi.org/10.1056/NEJM199603073341008CrossRefPubMedGoogle Scholar
  80. Engel J (1996b) Introduction to temporal lobe epilepsy. Epilepsy Res 26:141–150. https://doi.org/10.1016/S0920-1211(96)00043-5CrossRefPubMedGoogle Scholar
  81. Etherington LV, Frenguelli BG (2004) Endogenous adenosine modulates epileptiform activity in rat hippocampus in a receptor subtype-dependent manner. Eur J Neurosci 19:2539–2550. https://doi.org/10.1111/j.0953-816X.2004.03355.xCrossRefPubMedGoogle Scholar
  82. Etherington LA, Patterson GE, Meechan L et al (2009) Astrocytic adenosine kinase regulates basal synaptic adenosine levels and seizure activity but not activity-dependent adenosine release in the hippocampus. Neuropharmacology 56:429–437. https://doi.org/10.1016/j.neuropharm.2008.09.016CrossRefPubMedGoogle Scholar
  83. Faingold CL, Randall M, Kommajosyula SP (2016) Susceptibility to seizure-induced sudden death in DBA/2 mice is altered by adenosine. Epilepsy Res 124:49–54. https://doi.org/10.1016/j.eplepsyres.2016.05.007CrossRefPubMedGoogle Scholar
  84. Fedele DE, Li T, Lan JQ et al (2006) Adenosine A1 receptors are crucial in keeping an epileptic focus localized. Exp Neurol 200:184–190. https://doi.org/10.1016/j.expneurol.2006.02.133CrossRefPubMedGoogle Scholar
  85. Fiebich BL, Biber K, Lieb K et al (1996) Cyclooxygenase-2 expression in rat microglia is induced by adenosine A2a-receptors. Glia 18:152–160 doi: 10.1002/(SICI)1098-1136(199610)18:2<152::AID-GLIA7>3.0.CO;2-2CrossRefPubMedGoogle Scholar
  86. Fields RD, Burnstock G (2006) Purinergic signalling in neuron-glia interactions. Nat Rev Neurosci 7:423–436. https://doi.org/10.1038/nrn1928CrossRefPubMedPubMedCentralGoogle Scholar
  87. Fisher RS, Van Emde BW, Blume W et al (2005) Epileptic seizures and epilepsy: Definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia 46:470–472. https://doi.org/10.1111/j.0013-9580.2005.66104.xCrossRefPubMedGoogle Scholar
  88. Fisher RS, Acevedo C, Arzimanoglou A et al (2014) ILAE Official Report: A practical clinical definition of epilepsy. Epilepsia 55:475–482. https://doi.org/10.1111/epi.12550CrossRefPubMedGoogle Scholar
  89. Fisher RS, Cross JH, D’Souza C et al (2017) Instruction manual for the ILAE 2017 operational classification of seizure types. Epilepsia 58:531–542. https://doi.org/10.1111/epi.13671CrossRefPubMedGoogle Scholar
  90. Franklin PH, Zhang G, Tripp ED, Murray TF (1989) Adenosine A1 receptor activation mediates suppression of (-) bicuculline methiodide-induced seizures in rat prepiriform cortex. J Pharmacol Exp Ther 251:1229–1236PubMedGoogle Scholar
  91. Fujiwara Y, Sato M, Otsuki S (1986) Interaction of carbamazepine and other drugs with adenosine (A1and A2) receptors. Psychopharmacology (Berl) 90:332–335. https://doi.org/10.1007/BF00179186CrossRefGoogle Scholar
  92. Fukuda M, Suzuki Y, Hino H et al (2010) Adenosine A1 receptor blockage mediates theophylline-associated seizures. Epilepsia 51:483–487. https://doi.org/10.1111/j.1528-1167.2009.02382.xCrossRefPubMedGoogle Scholar
  93. Gebicke-Haerter PJ, Christoffel F, Timmer J et al (1996) Both adenosine A1- and A2-receptors are required to stimulate microglial proliferation. Neurochem Int 29:37–42. https://doi.org/10.1016/0197-0186(95)00137-9CrossRefPubMedGoogle Scholar
  94. Giraldez L, Girardi E (1998) Modification of [3H]MK801 binding to rat brain NMDA receptors after the administration of a convulsant drug and an adenosine analogue: A quantitative autoradiographic study. Neurochem Res 23:1327–1336. https://doi.org/10.1023/A:1020708603495CrossRefPubMedGoogle Scholar
  95. Girardi ES, Canitrot J, Antonelli M et al (2007) Differential expression of cerebellar metabotropic glutamate receptors mGLUR2/3 and mGLUR4a after the administration of a convulsant drug and the adenosine analogue cyclopentyladenosine. Neurochem Res 32:1120–1128. https://doi.org/10.1007/s11064-006-9275-8CrossRefPubMedGoogle Scholar
  96. Girardi E, Auzmendi J, Charó N et al (2010) 3-mercaptopropionic acid-induced seizures decrease NR2B expression in Purkinje cells: Cyclopentyladenosine effect. Cell Mol Neurobiol 30:985–990. https://doi.org/10.1007/s10571-010-9546-4CrossRefPubMedGoogle Scholar
  97. Glass M, Faull RL, Bullock JY et al (1996) Loss of A1 adenosine receptors in human temporal lobe epilepsy. Brain Res 710:56–68CrossRefPubMedGoogle Scholar
  98. Gleiter CH, Deckert J, Nutt DJ, Marangos PJ (1989) Electroconvulsive Shock (ECS) and the Adenosine Neuromodulatory System: Effect of Single and Repeated ECS on the Adenosine A1 and A2 Receptors, Adenylate Cyclase, and the Adenosine Uptake Site. J Neurochem 52:641–646. https://doi.org/10.1111/j.1471-4159.1989.tb09168.xCrossRefPubMedGoogle Scholar
  99. Goddard GV (1967) Development of epileptic seizures through brain stimulation at low intensity. Nature 214:1020–1021. https://doi.org/10.1038/2141020a0CrossRefPubMedGoogle Scholar
  100. Goddard GV, McIntyre DC, Leech CK (1969) A permanent change in brain function resulting from daily electrical stimulation. Exp Neurol 25:295–330. https://doi.org/10.1016/0014-4886(69)90128-9CrossRefPubMedGoogle Scholar
  101. Gouder N (2004) Overexpression of Adenosine Kinase in Epileptic Hippocampus Contributes to Epileptogenesis. J Neurosci 24:692–701. https://doi.org/10.1523/JNEUROSCI.4781-03.2004CrossRefPubMedGoogle Scholar
  102. Granata T, Marchi N, Carlton E et al (2009) Management of the patient with medically refractory epilepsy. Expert Rev Neurother 9:1791–1802. https://doi.org/10.1586/ern.09.114CrossRefPubMedPubMedCentralGoogle Scholar
  103. Güttinger M, Fedele D, Koch P et al (2005a) Suppression of kindled seizures by paracrine adenosine release from stem cell-derived brain implants. Epilepsia 46:1162–1169. https://doi.org/10.1111/j.1528-1167.2005.61804.xCrossRefPubMedGoogle Scholar
  104. Güttinger M, Padrun V, Pralong WF, Boison D (2005b) Seizure suppression and lack of adenosine A1receptor desensitization after focal long-term delivery of adenosine by encapsulated myoblasts. Exp Neurol 193:53–64. https://doi.org/10.1016/j.expneurol.2004.12.012CrossRefPubMedGoogle Scholar
  105. Hamil NE, Cock HR, Walker MC (2012) Acute down-regulation of adenosine A(1) receptor activity in status epilepticus. Epilepsia 53:177–188. https://doi.org/10.1111/j.1528-1167.2011.03340.xCrossRefPubMedGoogle Scholar
  106. Hammond JR, Paterson AR, Clanachan AS (1981) Benzodiazepine inhibition of site-specific binding of nitrobenzylthioinosine, an inhibitor of adenosine transport. Life Sci 29:2207–2214CrossRefPubMedGoogle Scholar
  107. Hargus NJ, Jennings C, Perez-Reyes E et al (2012) Enhanced actions of adenosine in medial entorhinal cortex layer II stellate neurons in temporal lobe epilepsy are mediated via A(1)-receptor activation. Epilepsia 53:168–176. https://doi.org/10.1111/j.1528-1167.2011.03337.xCrossRefPubMedGoogle Scholar
  108. Heidarianpour A, Sadeghian E, Mirnajafi-Zadeh J et al (2006) Anticonvulsant effects of N6-cyclohexyladenosine microinjected into the CA1 region of the hippocampus on entorhinal cortex-kindled seizures in rats. Epileptic Disord 8:259–266. https://doi.org/10.1684/epd.2006.0037CrossRefPubMedGoogle Scholar
  109. Heinemann U, Kann O, Remy S, Beck H (2006) Novel mechanisms underlying drug resistance in temporal lobe epilepsy. Adv Neurol 97:85–95PubMedGoogle Scholar
  110. Henshall DC, Kobow K (2015) Epigenetics and Epilepsy. Cold Spring Harb Perspect Med 5:715–736. https://doi.org/10.1101/cshperspect.a022731CrossRefGoogle Scholar
  111. Hoehn K, White TD (1990a) Role of excitatory amino acid receptors in K+- and glutamate-evoked release of endogenous adenosine from rat cortical slices. J Neurochem 54:256–265CrossRefPubMedGoogle Scholar
  112. Hoehn K, White TD (1990b) N-methyl-D-aspartate, kainate and quisqualate release endogenous adenosine from rat cortical slices. Neuroscience 39:441–450CrossRefPubMedGoogle Scholar
  113. Horan RL, Antle K, Collette AL et al (2005) In vitro degradation of silk fibroin. Biomaterials 26:3385–3393. https://doi.org/10.1016/j.biomaterials.2004.09.020CrossRefPubMedGoogle Scholar
  114. Hosseinmardi N, Mirnajafi-Zadeh J, Fathollahi Y, Shahabi P (2007) The role of adenosine A1 and A2A receptors of entorhinal cortex on piriform cortex kindled seizures in rats. Pharmacol Res 56:110–117. https://doi.org/10.1016/j.phrs.2007.04.011CrossRefPubMedGoogle Scholar
  115. Huber A, Padrun V, Déglon N et al (2001) Grafts of adenosine-releasing cells suppress seizures in kindling epilepsy. Proc Natl Acad Sci U S A 98:7611–7616. https://doi.org/10.1073/pnas.131102898CrossRefPubMedPubMedCentralGoogle Scholar
  116. Huber A, Güttinger M, Möhler H, Boison D (2002) Seizure suppression by adenosine A(2A) receptor activation in a rat model of audiogenic brainstem epilepsy. Neurosci Lett 329:289–292CrossRefPubMedGoogle Scholar
  117. Ilie A, Raimondo JV, Akerman CJ (2012) Adenosine release during seizures attenuates GABAA receptor-mediated depolarization. J Neurosci 32:5321–5332. https://doi.org/10.1523/JNEUROSCI.5412-11.2012CrossRefPubMedGoogle Scholar
  118. Ivanov AI, Bernard C (2017) Hippocampus in vitro. In: Models of seizures and epilepsy, 2nd edn. Elsevier Inc., United Kingdom, pp 261–272Google Scholar
  119. Jacobson KA, Merighi S, Varani K, et al (2017) A3adenosine receptors as modulators of inflammation: from medicinal chemistry to therapy. Med Res Rev 1–42. doi: https://doi.org/10.1002/med.21456
  120. James SJ, Melnyk S, Pogribna M et al (2002) Elevation in S-adenosylhomocysteine and DNA hypomethylation: potential epigenetic mechanism for homocysteine-related pathology. J Nutr 132:2361S–2366SCrossRefGoogle Scholar
  121. Janusz CA, Berman RF (1992) The A2-selective adenosine analog, CGS 21680, depresses locomotor activity but does not block amygdala kindled seizures in rats. Neurosci Lett 141:247–250. https://doi.org/10.1016/0304-3940(92)90905-MCrossRefPubMedGoogle Scholar
  122. Jones P, Smith R, Stone T (1998a) Protection against kainate-induced excitotoxicity by adenosine A2A receptor agonists and antagonists. Neuroscience 85:229–237. https://doi.org/10.1016/S0306-4522(97)00613-1CrossRefPubMedGoogle Scholar
  123. Jones PA, Smith RA, Stone TW (1998b) Protection against hippocampal kainate excitotoxicity by intracerebral administration of an adenosine A2A receptor antagonist. Brain Res 800:328–335CrossRefPubMedGoogle Scholar
  124. Kaila K, Lamsa K, Smirnov S et al (1997) Long-lasting GABA-mediated depolarization evoked by high-frequency stimulation in pyramidal neurons of rat hippocampal slice is attributable to a network-driven, bicarbonate-dependent K+ transient. J Neurosci 17:7662–7672CrossRefPubMedGoogle Scholar
  125. Kaku T, Jiang MH, Hada J et al (2001) Sodium nitroprusside-induced seizures and adenosine release in rat hippocampus. Eur J Pharmacol 413:199–205. https://doi.org/10.1016/S0014-2999(01)00763-4CrossRefPubMedGoogle Scholar
  126. Kaplan GB, Cotreau MM, Greenblatt DJ (1992) Effects of benzodiazepine administration on A1 adenosine receptor binding in-vivo and ex-vivo. J Pharm Pharmacol 44:700–703CrossRefPubMedGoogle Scholar
  127. Khan GM, Smolders I, Ebinger G, Michotte Y (2000) Anticonvulsant effect and neurotransmitter modulation of focal and systemic 2-chloroadenosine against the development of pilocarpine-induced seizures. Neuropharmacology 39:2418–2432CrossRefPubMedGoogle Scholar
  128. Khan GM, Smolders I, Ebinger G, Michotte Y (2001) 2-chloro-N(6)-cyclopentyladenosine-elicited attenuation of evoked glutamate release is not sufficient to give complete protection against pilocarpine-induced seizures in rats. Neuropharmacology 40:657–667CrossRefPubMedGoogle Scholar
  129. Kharazia VN, Prince DA (2001) Changes of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate receptors in layer V of epileptogenic, chronically isolated rat neocortex. Neuroscience 102:23–34 doi: S0306-4522(00)00467-X [pii]CrossRefPubMedGoogle Scholar
  130. Kiese K, Jablonski J, Boison D, Kobow K (2016) Dynamic regulation of the adenosine kinase gene during early postnatal brain development and maturation. Front Mol Neurosci 9. https://doi.org/10.3389/fnmol.2016.00099
  131. King AE, Ackley MA, Cass CE et al (2006) Nucleoside transporters: from scavengers to novel therapeutic targets. Trends Pharmacol Sci 27:416–425. https://doi.org/10.1016/j.tips.2006.06.004CrossRefPubMedGoogle Scholar
  132. Klaft ZJ, Schulz SB, Maslarova A et al (2012) Extracellular ATP differentially affects epileptiform activity via purinergic P2X7 and adenosine A1 receptors in naive and chronic epileptic rats. Epilepsia 53:1978–1986. https://doi.org/10.1111/j.1528-1167.2012.03724.xCrossRefPubMedGoogle Scholar
  133. Klitgaard H, Knutsen LJ, Thomsen C (1993) Contrasting effects of adenosine A1 and A2 receptor ligands in different chemoconvulsive rodent models. Eur J Pharmacol 242:221–228CrossRefPubMedGoogle Scholar
  134. Kochanek PM, Vagni VA, Janesko KL et al (2006) Adenosine A1 receptor knockout mice develop lethal status epilepticus after experimental traumatic brain injury. J Cereb Blood Flow Metab 26:565–575. https://doi.org/10.1038/sj.jcbfm.9600218CrossRefPubMedGoogle Scholar
  135. Kohl BK, Dannhardt G (2001) The NMDA receptor complex: a promising target for novel antiepileptic strategies. Curr Med Chem 8:1275–1289. https://doi.org/10.2174/0929867013372328CrossRefPubMedGoogle Scholar
  136. Kostopoulos GK, Limacher JJ, Phillis JW (1975) Action of various adenine derivatives on cerebellar Purkinje cells. Brain Res 88:162–165CrossRefPubMedGoogle Scholar
  137. Kulkarni C, Joseph T, David J (1991) Influence of adenosine receptor antagonists, aminophylline and caffeine, on seizure protective ability of antiepileptic drugs in rats. Indian J Exp Biol 29:751–754PubMedGoogle Scholar
  138. Kuroda Y, Kobayashi K (1975) Effects of Adenosine and Adenine Nucleotides on the Posts ynaptic Potential and on the Formation of Cyclic Adenosine 3 ’, 5 ’. Monophosphate from Radioactive Adenosine Triphosphate in Guinea Pig Olfactory Cortex Slices. Proc Jpn Acad 51:495–500CrossRefGoogle Scholar
  139. Kwan P, Brodie MJ (2001) Effectiveness of first antiepileptic drug. Epilepsia 42:1255–1260. https://doi.org/10.1046/j.1528-1157.2001.04501.xCrossRefPubMedGoogle Scholar
  140. Lambert NA, Teyler TJ (1991) Adenosine depresses excitatory but not fast inhibitory synaptic transmission in area CA1 of the rat hippocampus. Neurosci Lett 122:50–52. https://doi.org/10.1016/0304-3940(91)90190-90195CrossRefPubMedGoogle Scholar
  141. Lambrechts DAJE, de Kinderen RJA, Vles JSH et al (2017) A randomized controlled trial of the ketogenic diet in refractory childhood epilepsy. Acta Neurol Scand 135:231–239. https://doi.org/10.1111/ane.12592CrossRefPubMedGoogle Scholar
  142. Lancaster E, Dalmau J (2012) Neuronal autoantigens—pathogenesis, associated disorders and antibody testing. Nat Rev Neurol 8:380–390. https://doi.org/10.1038/nrneurol.2012.99CrossRefPubMedPubMedCentralGoogle Scholar
  143. Laudadio MA, Psarropoulou C (2004) The A3 adenosine receptor agonist 2-Cl-IB-MECA facilitates epileptiform discharges in the CA3 area of immature rat hippocampal slices. Epilepsy Res 59:83–94. https://doi.org/10.1016/j.eplepsyres.2004.03.005CrossRefPubMedGoogle Scholar
  144. Lee KS, Schubert P, Heinemann U (1984) The anticonvulsive action of adenosine: a postsynaptic, dendritic action by a possible endogenous anticonvulsant. Brain Res 321:160–164. https://doi.org/10.1016/0006-8993(84)90694-2CrossRefPubMedGoogle Scholar
  145. Lewin E, Bleck V (1977) Cyclic AMP Accumulation in Cerebral Cortical Slices: Effect of Carbamazepine, Phenobarbital, and Phenytoin. Epilepsia 18:237–242. https://doi.org/10.1111/j.1528-1157.1977.tb04472.xCrossRefPubMedGoogle Scholar
  146. Lewin E, Bleck V (1981) Electroshock Seizures in Mice: Effect on Brain Adenosine and Its Metabolites. Epilepsia 22:577–581. https://doi.org/10.1111/j.1528-1157.1981.tb04129.xCrossRefPubMedGoogle Scholar
  147. Li H, Henry JL (1992) Adenosine-induced hyperpolarization is depressed by glibenclamide in rat CA1 neurones. Neuroreport 3:1113–1116CrossRefPubMedGoogle Scholar
  148. Li T, Quan Lan J, Fredholm BB et al (2007a) Adenosine dysfunction in astrogliosis: cause for seizure generation? Neuron Glia Biol 3:353–366. https://doi.org/10.1017/S1740925X0800015XCrossRefPubMedPubMedCentralGoogle Scholar
  149. Li T, Steinbeck JA, Lusardi T et al (2007b) Suppression of kindling epileptogenesis by adenosine releasing stem cell-derived brain implants. Brain 130:1276–1288. https://doi.org/10.1093/brain/awm057CrossRefPubMedGoogle Scholar
  150. Li T, Ren G, Lusardi T et al (2008) Adenosine kinase is a target for the prediction and prevention of epileptogenesis in mice. J Clin Invest 118:571–582. https://doi.org/10.1172/JCI33737CrossRefPubMedPubMedCentralGoogle Scholar
  151. Li T, Ren G, Kaplan DL, Boison D (2009) Human mesenchymal stem cell grafts engineered to release adenosine reduce chronic seizures in a mouse model of CA3-selective epileptogenesis. Epilepsy Res 84:238–241. https://doi.org/10.1016/j.eplepsyres.2009.01.002CrossRefPubMedPubMedCentralGoogle Scholar
  152. Li T, Lytle N, Lan JQ et al (2012a) Local disruption of glial adenosine homeostasis in mice associates with focal electrographic seizures: A first step in epileptogenesis? Glia 60:83–95. https://doi.org/10.1002/glia.21250CrossRefPubMedGoogle Scholar
  153. Li X, Kang H, Liu X et al (2012b) Effect of adenosine A2A receptor antagonist ZM241385 on amygdala-kindled seizures and progression of amygdala kindling. J Huazhong Univ Sci Technolog Med Sci 32:257–264. https://doi.org/10.1007/s11596-012-0046-2CrossRefPubMedGoogle Scholar
  154. Li M, Kang R, Shi J et al (2013) Anticonvulsant Activity of B2, an Adenosine Analog, on Chemical Convulsant-Induced Seizures. PLoS One 8:1–10. https://doi.org/10.1371/journal.pone.0067060CrossRefGoogle Scholar
  155. Lie AA, Blümcke I, Beck H et al (1999) 5’-Nucleotidase activity indicates sites of synaptic plasticity and reactive synaptogenesis in the human brain. J Neuropathol Exp Neurol 58:451–458CrossRefPubMedGoogle Scholar
  156. Longo R, Zeng YC, Sagratella S (1995) Opposite modulation of 4-aminopyridine and hypoxic hyperexcitability by A1 and A2 adenosine receptor ligands in rat hippocampal slices. Neurosci Lett 200:21–24. https://doi.org/10.1016/0304-3940(95)12064-BCrossRefPubMedGoogle Scholar
  157. Lopes da Silva FH, Witter MP, Boeijinga PH, Lohman AH (1990) Anatomic organization and physiology of the limbic cortex. Physiol Rev 70:453–511CrossRefPubMedGoogle Scholar
  158. Löscher W (2011) Critical review of current animal models of seizures and epilepsy used in the discovery and development of new antiepileptic drugs. Seizure 20:359–368. https://doi.org/10.1016/j.seizure.2011.01.003CrossRefPubMedGoogle Scholar
  159. Löscher W, Gernert M, Heinemann U (2008) Cell and gene therapies in epilepsy - promising avenues or blind alleys? Trends Neurosci 31:62–73. https://doi.org/10.1016/j.tins.2007.11.012CrossRefPubMedGoogle Scholar
  160. Lovatt D, Xu Q, Liu W et al (2012) Neuronal adenosine release, and not astrocytic ATP release, mediates feedback inhibition of excitatory activity. Proc Natl Acad Sci 109:6265–6270. https://doi.org/10.1073/pnas.1120997109CrossRefPubMedGoogle Scholar
  161. Luan G, Wang X, Gao Q et al (2017) Upregulation of neuronal adenosine A1receptor in human Rasmussen encephalitis. J Neuropathol Exp Neurol 76:720–731. https://doi.org/10.1093/jnen/nlx053CrossRefPubMedGoogle Scholar
  162. Ma DK, Jang M-H, Guo J et al (2009) Neuronal activity-induced Gadd45b promotes epigentic DNA and adult neurogenesis. Science (80- ) 323:1070–1074CrossRefGoogle Scholar
  163. MacDonald RL, Skerritt JH, Werz MA (1986) Adenosine agonists reduce voltage-dependent calcium conductance of mouse sensory neurones in cell culture. J Physiol 370:75–90CrossRefPubMedPubMedCentralGoogle Scholar
  164. Malhotra J, Gupta YK (1997) Effect of adenosine receptor modulation on pentylenetetrazole-induced seizures in rats. Br J Pharmacol 120:282–288. https://doi.org/10.1038/sj.bjp.0700869CrossRefPubMedPubMedCentralGoogle Scholar
  165. Malhotra J, Seth SD, Gupta SK, Gupta YK (1996) Adenosinergic mechanisms in anticonvulsant action of diazepam and sodium valproate. Environ Toxicol Pharmacol 1:269–277. https://doi.org/10.1016/1382-6689(96)00020-8CrossRefPubMedGoogle Scholar
  166. Manzoni OJ, Manabe T, Nicoll RA (1994) Release of adenosine by activation of NMDA receptors in the hippocampus. Science 265:2098–2101CrossRefPubMedGoogle Scholar
  167. Marangos PJ, Post RM, Patel J et al (1983) Specific and potent interactions of carbamazepine with brain adenosine receptors. Eur J Pharmacol 93:175–182. https://doi.org/10.1016/0014-2999(83)90135-8CrossRefPubMedGoogle Scholar
  168. Marangos PJ, Weiss SRB, Montgomery P et al (1985) Chronic Carbamazepine Treatment Increases Brain Adenosine Receptors. Epilepsia 26:493–498. https://doi.org/10.1111/j.1528-1157.1985.tb05686.xCrossRefPubMedGoogle Scholar
  169. Marcoli M, Raiteri L, Bonfanti A et al (2003) Sensitivity to selective adenosine A1 and A2A receptor antagonists of the release of glutamate induced by ischemia in rat cerebrocortical slices. Neuropharmacology 45:201–210. https://doi.org/10.1016/S0028-3908(03)00156-4CrossRefPubMedGoogle Scholar
  170. Mareš P (2010) Anticonvulsant action of 2-chloroadenosine against pentetrazol-induced seizures in immature rats is due to activation of A1 adenosine receptors. J Neural Transm 117:1269–1277. https://doi.org/10.1007/s00702-010-0465-9CrossRefPubMedGoogle Scholar
  171. Masino SA, Geiger JD (2008) Are purines mediators of the anticonvulsant/neuroprotective effects of ketogenic diets? Trends Neurosci 31:273–278. https://doi.org/10.1016/j.tins.2008.02.009CrossRefPubMedPubMedCentralGoogle Scholar
  172. Masino SA, Geiger JD (2009) The ketogenic diet and epilepsy: Is adenosine the missing link? Epilepsia 50:332–333. https://doi.org/10.1111/j.1528-1167.2008.01771.xCrossRefPubMedGoogle Scholar
  173. Masino SA, Li T, Theofilas P et al (2011) A ketogenic diet suppresses seizures in mice through adenosine A3 receptors. J Clin Invest 121:2679–2683. https://doi.org/10.1172/JCI57813CrossRefPubMedPubMedCentralGoogle Scholar
  174. Masino SA, Kawamura M, Ruskin DN et al (2012) Purines and neuronal excitability: Links to the ketogenic diet. Epilepsy Res 100:229–238. https://doi.org/10.1016/j.eplepsyres.2011.07.014CrossRefPubMedGoogle Scholar
  175. Masino SA, Kawamura M, Ruskin DN (2014) Adenosine receptors and epilepsy. Current evidence and future potential. In: Adenosine Receptors in Neurology and Psychiatry, 1st edn. Elsevier Inc., United Kindom, p 233–255Google Scholar
  176. Massey CA, Sowers LP, Dlouhy BJ, Richerson GB (2014) Mechanisms of sudden unexpected death in epilepsy: The pathway to prevention. Nat Rev Neurol 10:271–282. https://doi.org/10.1038/nrneurol.2014.64CrossRefPubMedPubMedCentralGoogle Scholar
  177. Melani A, Pantoni L, Bordoni F et al (2003) The selective A2A receptor antagonist SCH 58261 reduces striatal transmitter outflow, turning behavior and ischemic brain damage induced by permanent focal ischemia in the rat. Brain Res 959:243–250. https://doi.org/10.1016/S0006-8993(02)03753-8CrossRefPubMedGoogle Scholar
  178. Miller-Delaney SFC, Bryan K, Das S et al (2015) Differential DNA methylation profiles of coding and non-coding genes define hippocampal sclerosis in human temporal lobe epilepsy. Brain 138:616–631. https://doi.org/10.1093/brain/awu373CrossRefPubMedGoogle Scholar
  179. Mirnajafi-Zadeh J, Pourgholami MH, Palizvan MR et al (1999) Anticonvulsant action of 2-chloroadenosine injected focally into the perirhinal cortex in amygdaloid kindled rats. Epilepsy Res 37:37–43. https://doi.org/10.1016/S0920-1211(99)00025-XCrossRefPubMedGoogle Scholar
  180. Mirnajafi-Zadeh J, Fathollahi Y, Pourgholami MH (2000) Intraperitoneal and intraamygdala N6-cyclohexyladenosine suppress hippocampal kindled seizures in rats. Brain Res 858:48–54. https://doi.org/10.1016/S0006-8993(99)02425-7CrossRefPubMedGoogle Scholar
  181. Mohammad-Zadeh M, Amini A, Mirnajafi-Zadeh J, Fathollahi Y (2005) The role of adenosine A1 receptors in the interaction between amygdala and entorhinal cortex of kindled rats. Epilepsy Res 65:1–9. https://doi.org/10.1016/j.eplepsyres.2005.03.012CrossRefPubMedGoogle Scholar
  182. Morrisett RA, Jope RS, Snead OC (1987) Effects of drugs on the initiation and maintenance of status epilepticus induced by administration of pilocarpine to lithium-pretreated rats. Exp Neurol 97:193–200. https://doi.org/10.1016/0014-4886(87)90293-7CrossRefPubMedGoogle Scholar
  183. Moschovos C, Kostopoulos G, Papatheodoropoulos C (2012) Endogenous adenosine induces NMDA receptor-independent persistent epileptiform discharges in dorsal and ventral hippocampus via activation of A2 receptors. Epilepsy Res 100:157–167. https://doi.org/10.1016/j.eplepsyres.2012.02.012CrossRefPubMedGoogle Scholar
  184. Muzzi M, Coppi E, Pugliese AM, Chiarugi A (2013) Anticonvulsant effect of AMP by direct activation of adenosine A1 receptor. Exp Neurol 250:189–193. https://doi.org/10.1016/j.expneurol.2013.09.010CrossRefPubMedGoogle Scholar
  185. Nagy AK, Houser CR, Delgado-Escueta AV (1990) Synaptosomal ATPase activities in temporal cortex and hippocampal formation of humans with focal epilepsy. Brain Res 529:192–201CrossRefPubMedGoogle Scholar
  186. Narimatsu E, Aoki M (1999) Involvement of the adenosine neuromodulatory system in the benzodiazepine-induced depression of excitatory synaptic transmissions in rat hippocampal neurons in vitro. Neurosci Res 33:57–64. https://doi.org/10.1016/S0168-0102(98)00110-2CrossRefPubMedGoogle Scholar
  187. Neal EG, Chaffe H, Schwartz RH et al (2008) The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial. Lancet Neurol 7:500–506. https://doi.org/10.1016/S1474-4422(08)70092-9CrossRefPubMedGoogle Scholar
  188. Newman M, Zohar J, Kalian M, Belmaker RH (1984) The effects of chronic lithium and ECT on A1 and A2 adenosine receptor systems in rat brain. Brain Res 291:188–192. https://doi.org/10.1016/0006-8993(84)90670-XCrossRefPubMedGoogle Scholar
  189. Niemand D, Martinell S, Arvidsson S et al (1984) Aminophylline inhibition of diazepam sedation: is adenosine blockade of GABA-receptors the mechanism? Lancet (London, England) 1:463–464CrossRefGoogle Scholar
  190. Niemand D, Martinell S, Arvidsson S et al (1986) Adenosine in the inhibition of diazepam sedation by aminophylline. Acta Anaesthesiol Scand 30:493–495CrossRefPubMedGoogle Scholar
  191. Nilsen KE, Cock HR (2004) Focal treatment for refractory epilepsy: Hope for the future? Brain Res Rev 44:141–153. https://doi.org/10.1016/j.brainresrev.2003.11.003CrossRefPubMedGoogle Scholar
  192. Nowak L, Bregestovski P, Ascher P et al (1984) Magnesium gates glutamate-activated channels in mouse central neurones. Nature 307:462–465. https://doi.org/10.1038/307462a0CrossRefPubMedGoogle Scholar
  193. O’Shaughnessy CT, Aram JA, Lodge D (1988) A1 adenosine receptor-mediated block of epileptiform activity induced in zero magnesium in rat neocortex in vitro. Epilepsy Res 2:294–301. https://doi.org/10.1016/0920-1211(88)90037-XCrossRefPubMedGoogle Scholar
  194. Ochiishi T, Takita M, Ikemoto M et al (1999) Immunohistochemical analysis on the role of adenosine A1 receptors in epilepsy. Neuroreport 10:3535–3541CrossRefPubMedGoogle Scholar
  195. Orr AG, Hsiao EC, Wang MM et al (2015) Astrocytic adenosine receptor A2A and Gs-coupled signaling regulate memory. Nat Neurosci 18:1–17. https://doi.org/10.1038/nn.3930CrossRefGoogle Scholar
  196. Ortiz F, Gutiérrez R (2015) Entorhinal cortex lesions result in adenosine-sensitive high frequency oscillations in the hippocampus. Exp Neurol 271:319–328. https://doi.org/10.1016/j.expneurol.2015.06.009CrossRefPubMedGoogle Scholar
  197. Pagonopoulou O, Angelatou F (1998) Time development and regional distribution of [3H]nitrobenzylthioinosine adenosine uptake site binding in the mouse brain after acute pentylenetetrazol-induced seizures. J Neurosci Res 53:433–442. https://doi.org/10.1002/(SICI)1097-4547(19980815)53:4<433::AID-JNR5>3.0.CO;2-7CrossRefPubMedGoogle Scholar
  198. Pagonopoulou O, Angelatou F, Kostopoulos G (1993) Effect of pentylenetetrazol-induced seizures on A1 adenosine receptor regional density in the mouse brain: a quantitative autoradiographic study. Neuroscience 56:711–716CrossRefPubMedGoogle Scholar
  199. Pascual O, Casper KB, Kubera C et al (2005) Astrocytic purinergic signaling coordinates synaptic networks. Science 310:113–116. https://doi.org/10.1126/science.1116916CrossRefPubMedGoogle Scholar
  200. Payne NE, Cross JH, Sander JW, Sisodiya SM (2011) The ketogenic and related diets in adolescents and adults--a review. Epilepsia 52:1941–1948. https://doi.org/10.1111/j.1528-1167.2011.03287.xCrossRefPubMedGoogle Scholar
  201. Petersen EN (1991) Selective protection by adenosine receptor agonists against DMCM-induced seizures. Eur J Pharmacol 195:261–265CrossRefPubMedGoogle Scholar
  202. Phillis JW (1984) Interactions of the anticonvulsants diphenylhydantoin and carbamazepine with adenosine on cerebral cortical neurons. Epilepsia 25:765–772CrossRefPubMedGoogle Scholar
  203. Phillis JW, Kostopoulos GK (1975) Adenosine as a putative transmitter in the cerebral cortex. Studies with potentiators and antagonists. Life Sci 17:1085–1094CrossRefPubMedGoogle Scholar
  204. Phillis JW, Wu PH (1982) The effect of various centrally active drugs on adenosine uptake by the central nervous system. Comp Biochem Physiol Part C, Comp 72:179–187. https://doi.org/10.1016/0306-4492(82)90082-XCrossRefGoogle Scholar
  205. Phillis JW, Kostopoulos GK, Limacher JJ (1974) Depression of corticospinal cells by various purines and pyrimidines. Can J Physiol Pharmacol 52:1226–1229CrossRefPubMedGoogle Scholar
  206. Pometlová M, Kubová H, Mareš P (2010) Effects of 2-chloroadenosine on cortical epileptic afterdischarges in immature rats. Pharmacol Reports 62:62–67. https://doi.org/10.1016/S1734-1140(10)70243-7CrossRefGoogle Scholar
  207. Popoli P, Pintor A, Domenici MR et al (2002) Blockade of striatal adenosine A2A receptor reduces, through a presynaptic mechanism, quinolinic acid-induced excitotoxicity: possible relevance to neuroprotective interventions in neurodegenerative diseases of the striatum. J Neurosci 22:1967–1975 doi: 22/5/1967 [pii]CrossRefPubMedGoogle Scholar
  208. Porkka-Heiskanen T, Strecker RE, Thakkar M et al (1997) Adenosine: a mediator of the sleep-inducing effects of prolonged wakefulness. Science 276:1265–1268CrossRefPubMedPubMedCentralGoogle Scholar
  209. Pourgholami MH, Mirnajafi-Zadeh J, Behzadi J (1997a) Effect of intraperitoneal and intrahippocampal (CA1) 2-chloroadenosine in amygdaloid kindled rats. Brain Res 751:259–264. https://doi.org/10.1016/S0006-8993(96)01406-0CrossRefPubMedGoogle Scholar
  210. Pourgholami MH, Rostampour M, Mirnajafi-Zadeh J, Palizvan MR (1997b) Intra-amygdala infusion of 2-chloroadenosine suppresses amygdala-kindled seizures. Brain Res 775:37–42CrossRefPubMedGoogle Scholar
  211. Prince DA, Stevens CF (1992) Adenosine decreases neurotransmitter release at central synapses. Proc Natl Acad Sci U S A 89:8586–8590. https://doi.org/10.1073/pnas.89.18.8586CrossRefPubMedPubMedCentralGoogle Scholar
  212. Psarropoulou C, Matsokis N, Angelatou F, Kostopoulos G (1994) Pentylenetetrazol-induced seizures decrease gamma-aminobutyric acid-mediated recurrent inhibition and enhance adenosine- mediated depression. Epilepsia 35:12–19CrossRefPubMedGoogle Scholar
  213. Pull I, McIlwain H (1972) Metabolism of ( 14 C)adenine and derivatives by cerebral tissues, superfused and electrically stimulated. Biochem J 126:965–973CrossRefPubMedPubMedCentralGoogle Scholar
  214. Raimondo JV, Heinemann U, de Curtis M et al (2017) Methodological standards for in vitro models of epilepsy and epileptic seizures. A TASK1-WG4 report of the AES/ILAE Translational Task Force of the ILAE. Epilepsia 58:40–52. https://doi.org/10.1111/epi.13901CrossRefPubMedGoogle Scholar
  215. Rebola N, Coelho JE, Costenla AR et al (2003) Decrease of adenosine A1 receptor density and of adenosine neuromodulation the hippocampus of kindled rats. Eur J Neurosci 18:820–828. https://doi.org/10.1046/j.1460-9568.2003.02815.xCrossRefPubMedGoogle Scholar
  216. Rebola N, Porciúncula LO, Lopes LV et al (2005) Long-term effect of convulsive behavior on the density of adenosine A1 and A 2A receptors in the rat cerebral cortex. Epilepsia 46(Suppl 5):159–165. https://doi.org/10.1111/j.1528-1167.2005.01026.xCrossRefPubMedGoogle Scholar
  217. Ren G, Li T, Lan JQ et al (2007) Lentiviral RNAi-induced downregulation of adenosine kinase in human mesenchymal stem cell grafts: A novel perspective for seizure control. Exp Neurol 208:26–37. https://doi.org/10.1016/j.expneurol.2007.07.016CrossRefPubMedPubMedCentralGoogle Scholar
  218. Rezvani ME, Mirnajafi-Zadeh J, Fathollahi Y, Palizvan MR (2007a) Anticonvulsant effect of A1 but not A2A adenosine receptors of piriform cortex in amygdala-kindled rats. Can J Physiol Pharmacol 85:606–612. https://doi.org/10.1139/y07-046CrossRefPubMedGoogle Scholar
  219. Rezvani ME, Mirnajafi-Zadeh J, Fathollahi Y, Palizvan MR (2007b) Changes in neuromodulatory effect of adenosine A1 receptors on piriform cortex field potentials in amygdala kindled rats. Eur J Pharmacol 565:60–67. https://doi.org/10.1016/j.ejphar.2007.02.010CrossRefPubMedGoogle Scholar
  220. Rice AC, Delorenzo RJ (1998) NMDA receptor activation during status epilepticus is required for the development of epilepsy. Brain Res 782:240–247. https://doi.org/10.1016/S0006-8993(97)01285-7CrossRefPubMedGoogle Scholar
  221. Richerson GB, Boison D, Faingold CL, Ryvlin P (2016) From unwitnessed fatality to witnessed rescue: Pharmacologic intervention in sudden unexpected death in epilepsy. Epilepsia 57:35–45. https://doi.org/10.1111/epi.13236CrossRefPubMedPubMedCentralGoogle Scholar
  222. Robledo P, Ursu G, Mahy N (1999) Effects of adenosine and gamma-aminobutyric acid A receptor antagonists on N-methyl-D-aspartate induced neurotoxicity in the rat hippocampus. Hippocampus 9:527–533. https://doi.org/10.1002/(SICI)1098-1063(1999)9:5<527::AID-HIPO6>3.0.CO;2-UCrossRefPubMedGoogle Scholar
  223. Rogawski MA, Löscher W, Rho JM (2016) Mechanisms of action of Antiseizure Drugs and the Ketogenic diet. Cold Spring Harb Perspect Med 6:28. https://doi.org/10.1101/cshperspect.a022780CrossRefGoogle Scholar
  224. Rombo DM, Newton K, Nissen W et al (2015) Synaptic mechanisms of adenosine A2A receptor-mediated hyperexcitability in the hippocampus. Hippocampus 25:566–580. https://doi.org/10.1002/hipo.22392CrossRefPubMedGoogle Scholar
  225. Rombo DM, Dias RB, Duarte ST et al (2016a) Adenosine A1 Receptor Suppresses Tonic GABAA Receptor Currents in Hippocampal Pyramidal Cells and in a Defined Subpopulation of Interneurons. Cereb Cortex 26:1081–1095. https://doi.org/10.1093/cercor/bhu288CrossRefPubMedGoogle Scholar
  226. Rombo DM, Ribeiro JA, Sebastião AM (2016b) Hippocampal GABAergic transmission: a new target for adenosine control of excitability. J Neurochem 139:1056–1070. https://doi.org/10.1111/jnc.13872CrossRefPubMedGoogle Scholar
  227. Rosen JB, Berman RF (1987) Differential Effects of Adenosine Analogs on Amygdala, Hippocampus, and Caudate Nucleus Kindled Seizures. Epilepsia 28:658–666. https://doi.org/10.1111/j.1528-1157.1987.tb03697.xCrossRefPubMedGoogle Scholar
  228. Roseti C, Martinello K, Fucile S et al (2008) Adenosine receptor antagonists alter the stability of human epileptic GABAA receptors. Proc Natl Acad Sci U S A 105:15118–15123. https://doi.org/10.1073/pnas.0807277105CrossRefPubMedPubMedCentralGoogle Scholar
  229. Roseti C, Palma E, Martinello K et al (2009) Blockage of A2A and A3 adenosine receptors decreases the desensitization of human GABA(A) receptors microtransplanted to Xenopus oocytes. Proc Natl Acad Sci U S A 106:15927–15931. https://doi.org/10.1073/pnas.0907324106CrossRefPubMedPubMedCentralGoogle Scholar
  230. Sandau US, Colino-Oliveira M, Jones A et al (2016) Adenosine Kinase Deficiency in the Brain Results in Maladaptive Synaptic Plasticity. J Neurosci 36:12117–12128. https://doi.org/10.1523/JNEUROSCI.2146-16.2016CrossRefPubMedPubMedCentralGoogle Scholar
  231. Sander JW, Shorvon SD (1996) Epidemiology of the epilepsies. J Neurol Neurosurg Psychiatry 61:433–443. https://doi.org/10.1136/jnnp.61.5.433CrossRefPubMedPubMedCentralGoogle Scholar
  232. Sato M, Racine RJ, McIntyre DC (1990) Kindling: basic mechanisms and clinical validity. Electroencephalogr Clin Neurophysiol 76:459–472. https://doi.org/10.1016/0013-4694(90)90099-6CrossRefPubMedGoogle Scholar
  233. Saura J, Angulo E, Ejarque A et al (2005) Adenosine A2A receptor stimulation potentiates nitric oxide release by activated microglia. J Neurochem 95:919–929. https://doi.org/10.1111/j.1471-4159.2005.03395.xCrossRefPubMedGoogle Scholar
  234. Scanziani M, Capogna M, Gähwiler BH, Thompson SM (1992) Presynaptic inhibition of miniature excitatory synaptic currents by baclofen and adenosine in the hippocampus. Neuron 9:919–927CrossRefPubMedGoogle Scholar
  235. Scheffer IE, Berkovic S, Capovilla G et al (2017) ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia 58:512–521. https://doi.org/10.1111/epi.13709CrossRefPubMedPubMedCentralGoogle Scholar
  236. Schindler CW, Karcz-Kubicha M, Thorndike EB et al (2005) Role of central and peripheral adenosine receptors in the cardiovascular responses to intraperitoneal injections of adenosine A 1 and A 2A subtype receptor agonists. Br J Pharmacol 144:642–650. https://doi.org/10.1038/sj.bjp.0706043CrossRefPubMedPubMedCentralGoogle Scholar
  237. Schoen SW, Ebert U, Löscher W (1999) 5’-Nucleotidase activity of mossy fibers in the dentate gyrus of normal and epileptic rats. Neuroscience 93:519–526. https://doi.org/10.1016/S0306-4522(99)00135-9CrossRefPubMedGoogle Scholar
  238. Scholfield CN (1978) Depression of evoked potentials in brain slices by adenosine compounds. Br J Pharmacol 63:239–244. https://doi.org/10.1111/j.1476-5381.1978.tb09752.xCrossRefPubMedPubMedCentralGoogle Scholar
  239. Scholz KP, Miller RJ (1992) Inhibition of quantal transmitter release in the absence of calcium influx by a G protein-linked adenosine receptor at hippocampal synapses. Neuron 8:1139–1150CrossRefPubMedGoogle Scholar
  240. Schrader J, Wahl M, Kuschinsky W, Kreutzberg GN (1980) Increase of adenosine content in cerebral cortex of the rat during bicuculline-induced seizures. Pfluegers Arch 387:245–251CrossRefGoogle Scholar
  241. Schrader J, Schütz W, Bardenheuer H (1981) Role of S-adenosylhomocysteine hydrolase in adenosine metabolism in mammalian heart. Biochem J 196:65–70CrossRefPubMedPubMedCentralGoogle Scholar
  242. Schubert P, Mitzdorf U (1979) Analysis and quantitative evaluation of the depressive effect of adenosine on evoked potentials in hippocampal slices. Brain Res 172:186–190CrossRefPubMedGoogle Scholar
  243. Schubert P, Heinemann U, Kolb R (1986) Differential effect of adenosine on pre- and postsynaptic calcium fluxes. Brain Res 376:382–386CrossRefPubMedGoogle Scholar
  244. Schultz V, Lowenstein JM (1978) The purine nucleotide cycle. Studies of ammonia production and interconversions of adenine and hypoxanthine nucleotides and nucleosides by rat brain in situ. J Biol Chem 253:1938–1943PubMedGoogle Scholar
  245. Sebastião AM, Ribeiro JA (2009) Adenosine receptors in health and disease. Springer Berlin Heidelberg, Berlin/HeidelbergGoogle Scholar
  246. Sebastião AM, Rombo DM, Ribeiro JA (2015) Adenosinergic receptor modulation of GABAergic transmission. In: Adenosine Signaling Mechanisms: Pharmacology, Functions and Therapeutic Aspects. Ramkunmar V, Paes de Carvalho R (editors). Nova Science Publishers, United States.Google Scholar
  247. Seifert G, Carmignoto G, Steinhäuser C (2010) Astrocyte dysfunction in epilepsy. Brain Res Rev 63:212–221. https://doi.org/10.1016/j.brainresrev.2009.10.004CrossRefPubMedGoogle Scholar
  248. Shahabi P, Mirnajafi-Zadeh J, Fathollahi Y et al (2006) Amygdala adenosine A1 receptors have no anticonvulsant effect on piriform cortex-kindled seizures in rat. Can J Physiol Pharmacol 84. https://doi.org/10.1139/Y06-041
  249. Shen HY, Li T, Boison D (2010) A novel mouse model for sudden unexpected death in epilepsy (SUDEP): Role of impaired adenosine clearance. Epilepsia 51:465–468. https://doi.org/10.1111/j.1528-1167.2009.02248.xCrossRefPubMedGoogle Scholar
  250. Shinohara M, Saitoh M, Nishizawa D et al (2013) ADORA2A polymorphism predisposes children to encephalopathy with febrile status epilepticus. Neurology 80:1571–1576. https://doi.org/10.1212/WNL.0b013e31828f18d8CrossRefPubMedPubMedCentralGoogle Scholar
  251. Skeritt JH, Davies LP, Johnston GA (1982) A purinergic component in the anticonvulsant action of carbamazepine? Eur J Pharmacol 82:195–197CrossRefPubMedGoogle Scholar
  252. Skerritt JH, Davies LP, Johnston GAR (1983) Interactions of the anticonvulsant carbamazepine with adenosine receptors. 1. Neurochemical studies. Epilepsia 24:634–642. https://doi.org/10.1111/j.1528-1157.1983.tb03429.xCrossRefPubMedGoogle Scholar
  253. Skolnick P, Lock KL, Paul SM et al (1980) Increased benzodiazepine receptor number elicited in vitro by a novel purine, EMD 28422. Eur J Pharmacol 67:179–186CrossRefPubMedGoogle Scholar
  254. Staley KJ, Soldo BL, Proctor WR (1995) Ionic mechanisms of neuronal excitation by inhibitory GABAA receptors. Science 269:977–981. https://doi.org/10.1126/science.7638623CrossRefPubMedGoogle Scholar
  255. Stella L, Berrino L, Maione S et al (1993) Cardiovascular effects of adenosine and its analogs in anaesthetized rats. Life Sci 53:755–763. https://doi.org/10.1016/0024-3205(93)90497-QCrossRefPubMedGoogle Scholar
  256. Studer FE, Fedele DE, Marowsky A et al (2006) Shift of adenosine kinase expression from neurons to astrocytes during postnatal development suggests dual functionality of the enzyme. Neuroscience 142:125–137. https://doi.org/10.1016/j.neuroscience.2006.06.016CrossRefPubMedGoogle Scholar
  257. Szybala C, Pritchard EM, Lusardi T et al (2009) Antiepileptic effects of silk-polymer based adenosine release in kindled rats. Exp Neurol 219:126–135. https://doi.org/10.1016/j.expneurol.2009.05.018CrossRefPubMedPubMedCentralGoogle Scholar
  258. Tchekalarova J, Sotiriou E, Georgiev V et al (2005) Up-regulation of adenosine A1 receptor binding in pentylenetetrazol kindling in mice: Effects of angiotensin IV. Brain Res 1032:94–103. https://doi.org/10.1016/j.brainres.2004.11.004CrossRefPubMedGoogle Scholar
  259. Theofilas P, Brar S, Stewart KA et al (2011) Adenosine kinase as a target for therapeutic antisense strategies in epilepsy. Epilepsia 52:589–601. https://doi.org/10.1111/j.1528-1167.2010.02947.xCrossRefPubMedPubMedCentralGoogle Scholar
  260. Thompson SM, Gähwiler BH (1989) Activity-dependent disinhibition. I. Repetitive stimulation reduces IPSP driving force and conductance in the hippocampus in vitro. J Neurophysiol 61:501–511CrossRefPubMedGoogle Scholar
  261. Thümmler S, Dunwiddie TV (2000) Adenosine receptor antagonists induce persistent bursting in the rat hippocampal CA3 region via an NMDA receptor-dependent mechanism. J Neurophysiol 83:1787–1795CrossRefPubMedGoogle Scholar
  262. Tosh DK, Paoletta S, Deflorian F et al (2012) Structural sweet spot for A1 adenosine receptor activation by truncated (N)-methanocarba nucleosides: receptor docking and potent anticonvulsant activity. J Med Chem 55:8075–8090. https://doi.org/10.1021/jm300965aCrossRefPubMedPubMedCentralGoogle Scholar
  263. Trussell LO, Jackson MB (1987) Dependence of an adenosine-activated potassium current on a GTP-binding protein in mammalian central neurons. J Neurosci 7:3306–3316CrossRefPubMedGoogle Scholar
  264. Turski WA, Cavalheiro EA, Ikonomidou C et al (1985) Effects of aminophylline and 2-chloroadenosine on seizures produced by pilocarpine in rats: Morphological and electroencephalographic correlates. Brain Res 361:309–323. https://doi.org/10.1016/0006-8993(85)91302-2CrossRefPubMedGoogle Scholar
  265. Uthman BM (2000) Vagus nerve stimulation therapy for seizures. Arch Med Res 31:300–303. https://doi.org/10.1097/ANA.0b013e31815b7df1CrossRefPubMedGoogle Scholar
  266. Uzbay TI, Kayir H, Ceyhan M (2007) Effects of tianeptine on onset time of pentylenetetrazole-induced seizures in mice: Possible role of adenosine A1 receptors. Neuropsychopharmacology 32:412–416. https://doi.org/10.1038/sj.npp.1301143CrossRefPubMedGoogle Scholar
  267. Van Gompel JJ, Bower MR, Worrell GA et al (2014) Increased cortical extracellular adenosine correlates with seizure termination. Epilepsia 55:233–244. https://doi.org/10.1111/epi.12511CrossRefPubMedPubMedCentralGoogle Scholar
  268. van Vliet EA, Aronica E, Vezzani A, Ravizza T (2018) Review: Neuroinflammatory pathways as treatment targets and biomarker candidates in epilepsy: emerging evidence from preclinical and clinical studies. Neuropathol Appl Neurobiol 44:91–111. https://doi.org/10.1111/nan.12444CrossRefPubMedGoogle Scholar
  269. Vandam RJ, Shields EJ, Kelty JD (2008) Rhythm generation by the pre-Bötzinger complex in medullary slice and island preparations: effects of adenosine A(1) receptor activation. BMC Neurosci 9:95. https://doi.org/10.1186/1471-2202-9-95CrossRefPubMedPubMedCentralGoogle Scholar
  270. Vanore G, Giraldez L, Rodríguez de Lores Arnaiz G, Girardi E (2001) Seizure activity produces differential changes in adenosine A1 receptors within rat hippocampus. Neurochem Res 26:225–230. https://doi.org/10.1023/A:1010912516299CrossRefPubMedGoogle Scholar
  271. Vezzani A, Fujinami RS, White HS et al (2016) Infections, inflammation and epilepsy. Acta Neuropathol 131:211–234. https://doi.org/10.1007/s00401-015-1481-1485CrossRefPubMedGoogle Scholar
  272. Vianna EPM, Ferreira AT, Doná F et al (2005) Modulation of seizures and synaptic plasticity by adenosinergic receptors in an experimental model of temporal lobe epilepsy induced by pilocarpine in rats. Epilepsia 46(Suppl 5):166–173. https://doi.org/10.1111/j.1528-1167.2005.01027.xCrossRefPubMedGoogle Scholar
  273. Von Lubitz DK, Paul IA, Carter M, Jacobson KA (1993) Effects of N6-cyclopentyl adenosine and 8-cyclopentyl-1,3-dipropylxanthine on N-methyl-D-aspartate induced seizures in mice. Eur J Pharmacol 249:265–270CrossRefGoogle Scholar
  274. Von Lubitz DK, Lin RC, Popik P et al (1994a) Adenosine A3 receptor stimulation and cerebral ischemia. Eur J Pharmacol 263:59–67. https://doi.org/10.1016/0014-2999(94)90523-1CrossRefGoogle Scholar
  275. Von Lubitz DK, Paul IA, Ji XD et al (1994b) Chronic adenosine A1 receptor agonist and antagonist: effect on receptor density and N-methyl-D-aspartate induced seizures in mice. EurJPharmacol 253:95–99. https://doi.org/10.1016/j.surg.2006.10.010.UseCrossRefGoogle Scholar
  276. Von Lubitz DK, Carter MF, Deutsch SI et al (1995a) The effects of adenosine A3 receptor stimulation on seizures in mice. Eur J Pharmacol 275:23–29. https://doi.org/10.1016/0014-2999(94)00734-OCrossRefGoogle Scholar
  277. Von Lubitz DKJE, Kim J, Beenhakker M et al (1995b) Chronic NMDA receptor stimulation: Therapeutic implications of its effect on adenosine A1 receptors. EurJPharmacol 283:185–192Google Scholar
  278. Wang S, Kurada L, Cilz NI et al (2013) Adenosinergic Depression of Glutamatergic Transmission in the Entorhinal Cortex of Juvenile Rats via Reduction of Glutamate Release Probability and the Number of Releasable Vesicles. PLoS One 8:1–10. https://doi.org/10.1371/journal.pone.0062185CrossRefGoogle Scholar
  279. Weir RL, Padgett W, Daly JW, Anderson SM (1984) Interaction of anticonvulsant drugs with adenosine receptors in the central nervous system. Epilepsia 25:492–498CrossRefPubMedGoogle Scholar
  280. Wheless JW (2008) History of the ketogenic diet. Epilepsia 49:3–5. https://doi.org/10.1111/j.1528-1167.2008.01821.xCrossRefPubMedGoogle Scholar
  281. Whitcomb K, Lupica CR, Rosen JB, Berman RF (1990) Adenosine involvement in postictal events in amygdala-kindled rats. Epilepsy Res 6:171–179. https://doi.org/10.1016/0920-1211(90)90070-CCrossRefPubMedGoogle Scholar
  282. Wieraszko A, Seyfried TN (1989) Increased amount of extracellular ATP in stimulated hippocampal slices of seizure prone mice. Neurosci Lett 106:287–293. https://doi.org/10.1016/0304-3940(89)90178-XCrossRefPubMedGoogle Scholar
  283. Williams M, Risley EA, Huff JR (1981) Interaction of putative anxiolytic agents with central adenosine receptors. Can J Physiol Pharmacol 59:897–900. https://doi.org/10.1139/y81-136CrossRefPubMedGoogle Scholar
  284. Williams-Karnesky RL, Sandau US, Lusardi TA et al (2013) Epigenetic changes induced by adenosine augmentation therapy prevent epileptogenesis. J Clin Invest 123:3552–3563. https://doi.org/10.1172/JCI65636CrossRefPubMedPubMedCentralGoogle Scholar
  285. Wilz A, Pritchard EM, Li T et al (2008) Silk polymer-based adenosine release: therapeutic potential for epilepsy. Biomaterials 29:3609–3616. https://doi.org/10.1016/j.biomaterials.2008.05.010CrossRefPubMedPubMedCentralGoogle Scholar
  286. Winn HR, Welsh JE, Rubio R, Berne RM (1980) Changes in brain adenosine during bicuculline-induced seizures in rats. Effects of hypoxia and altered systemic blood pressure. Circ Res 47:568–577. https://doi.org/10.1161/01.RES.47.4.568CrossRefPubMedGoogle Scholar
  287. Wirkner K, Gerevich Z, Krause T et al (2004) Adenosine A2A receptor-induced inhibition of NMDA and GABAA receptor-mediated synaptic currents in a subpopulation of rat striatal neurons. Neuropharmacology 46:994–1007. https://doi.org/10.1016/j.neuropharm.2004.01.008CrossRefPubMedGoogle Scholar
  288. Wu LG, Saggau P (1994) Adenosine inhibits evoked synaptic transmission primarily by reducing presynaptic calcium influx in area CA1 of hippocampus. Neuron 12:1139–1148. https://doi.org/10.1016/0896-6273(94)90321-2CrossRefPubMedGoogle Scholar
  289. Yoon KW, Rothman SM (1991) Adenosine inhibits excitatory but not inhibitory synaptic transmission in the hippocampus. J Neurosci 11:1375–1380. https://doi.org/10.4161/cib.3.5.12287CrossRefPubMedGoogle Scholar
  290. Young D, Dragunow M (1994) Status epilepticus may be caused by loss of adenosine anticonvulsant mechanisms. Neuroscience 58:245–261. https://doi.org/10.1016/0306-4522(94)90032-9CrossRefPubMedGoogle Scholar
  291. Zeraati M, Mirnajafi-Zadeh J, Fathollahi Y et al (2006) Adenosine A1 and A2A receptors of hippocampal CA1 region have opposite effects on piriform cortex kindled seizures in rats. Seizure 15:41–48. https://doi.org/10.1016/j.seizure.2005.10.006CrossRefPubMedGoogle Scholar
  292. Zgodziński W, Rubaj A, Kleinrok Z, Sieklucka-Dziuba M (2001) Effect of adenosine A1 and A2 receptor stimulation on hypoxia-induced convulsions in adult mice. Pol J Pharmacol 53:83–92CrossRefPubMedGoogle Scholar
  293. Zhang G, Franklin PH, Murray TF (1993) Manipulation of endogenous adenosine in the rat prepiriform cortex modulates seizure susceptibility. J Pharmacol Exp Ther 264:1415–1424PubMedGoogle Scholar
  294. Zhang G, Franklin PH, Murray TF (1994) Activation of adenosine A1 receptors underlies anticonvulsant effect of CGS21680. Eur J Pharmacol 255:239–243. https://doi.org/10.1016/0014-2999(94)90104-XCrossRefPubMedGoogle Scholar
  295. Zhang G, Raol YSH, Hsu F-C, Brooks-Kayal AR (2003) Long-term alterations in glutamate receptor and transporter expression following early-life seizures are associated with increased seizure susceptibility. J Neurochem 88:91–101. https://doi.org/10.1046/j.1471-4159.2003.02124.xCrossRefGoogle Scholar
  296. Zimmermann H (2000) Extracellular metabolism of ATP and other nucleotides. Naunyn Schmiedebergs Arch Pharmacol 362:299–309. https://doi.org/10.1007/s002100000309CrossRefPubMedGoogle Scholar
  297. Zimmermann H, Zebisch M, Sträter N (2012) Cellular function and molecular structure of ecto-nucleotidases. Purinergic Signal 8:437–502. https://doi.org/10.1007/s11302-012-9309-4CrossRefPubMedPubMedCentralGoogle Scholar
  298. Zuchora B, Turski WA, Wielosz M, Urbanska EM (2001) Protective effect of adenosine receptor agonists in a new model of epilepsy--seizures evoked by mitochondrial toxin, 3-nitropropionic acid, in mice. NeurosciLett 305:91–94Google Scholar
  299. Zuchora B, Wielosz M, Urbańska EM (2005) Adenosine A1 receptors and the anticonvulsant potential of drugs effective in the model of 3-nitropropionic acid-induced seizures in mice. Eur Neuropsychopharmacol 15:85–93. https://doi.org/10.1016/j.euroneuro.2004.05.006CrossRefPubMedGoogle Scholar
  300. Zwicker JD, Rajani V, Hahn LB, Funk GD (2011) Purinergic modulation of preBötzinger complex inspiratory rhythm in rodents: the interaction between ATP and adenosine. J Physiol 589:4583–4600. https://doi.org/10.1113/jphysiol.2011.210930CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Diogo Miguel Rombo
    • 1
    • 2
  • Joaquim Alexandre Ribeiro
    • 1
    • 2
  • Ana Maria Sebastião
    • 1
    • 2
  1. 1.Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de LisboaLisboaPortugal
  2. 2.Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de LisboaLisboaPortugal

Personalised recommendations