International Journal of Oral Biology

The Korean Academy of Oral Biology (대한구강생물학회)
권호 표지

Effects of Phenytoin and Diazepam on the Seizure Activity in the Cortical Dysplasia Animal Models

  • Kim, Si-Hyung (Department of Pediatric Dentistry, College of Dentistry, Kyungpook National University) ;
  • Choi, In-Sun (Department of Dental Pharmacology, College of Dentistry, Kyungpook National University) ;
  • Cho, Jin-Hwa (Department of Dental Pharmacology, College of Dentistry, Kyungpook National University) ;
  • Park, Eun-Ju (Department of Dental Pharmacology, College of Dentistry, Kyungpook National University) ;
  • Jang, Il-Sung (Department of Dental Pharmacology, College of Dentistry, Kyungpook National University) ;
  • Choi, Byung-Ju (Department of Dental Pharmacology, College of Dentistry, Kyungpook National University) ;
  • Kim, Hyun-Jung (Department of Pediatric Dentistry, College of Dentistry, Kyungpook National University) ;
  • Kim, Young-Jin (Department of Pediatric Dentistry, College of Dentistry, Kyungpook National University) ;
  • Nam, Soon-Hyeun (Department of Pediatric Dentistry, College of Dentistry, Kyungpook National University)
  • Published : 2006.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

Dysplasia-associated seizure disorders are markedly resistant to pharmacological intervention. Relatively little research has been conducted studying the effects of antiepileptic drugs(AEDs)on seizure activity in a rat model of dysplasia. We have used rats exposed to methylazoxymethanol acetate(MAM) in utero, an animal model featuring nodular heterotopia, to investigate the effects of AEDs in the dysplastic brain. Pilocarpine was used to induce acute seizure in MAM-exposed and age-matched vehicle-injected control animals. Field potential recordings were used to monitor amplitude and numbers of population spikes, and paired pulse inhibition in response to stimulation of commissural pathway. Two commonly used AEDs were tested: diazepam 5, 2.5 mg/kg; phenytoin 40, 60 mg/kg. Diazepam(DZP) and phenytoin(PHT) reduced the amplitude of population spike in control and MAM-exposed rats. However, the amplitude of population spike was nearly eliminated in control rats as compared to the MAM-exposed rats. Pharmaco-resistance was tested by measuring seizure latencies in awake rats after pilocarpine administration(320 mg/kg, i.p.) with and without pretreatment with AEDs. Pre-treatment with PHT 60 mg prolonged seizure latency in control rats, but not in MAM-exposed animals. The main findings of this study are that acute seizures initiated in MAM-exposed rats are relatively resistant to standard AEDs assessed in vivo. These data suggest that animal model with cortical dysplasia can be used to screen the effects of potential AEDs.

Keywords

References

  1. Aicardi, J.: The place of neuronal migration abnormalities in child neurology. Can. J. Neurol. Sci. 21(3):185-193, Review, 1994 https://doi.org/10.1017/S0317167100041159
  2. Amano, S., Ihara, N., Umeura, S.: Development of novel rat mutant with spontaneous limbic-like seizures. Am. J. Pathol. 149:329-336, 1996
  3. Baba, A., Okumura, S., Mizuo, H., Iwata, H.: The inhibition of diazepam and gamma-aminobutyric acid of depolarizationinduced release of (14C) cysteine sulfinate and (3H) glutamate in rat hippocampal slices. J. Neurochem. 40:280284, 1983 https://doi.org/10.1111/j.1471-4159.1983.tb12683.x
  4. Babb, T.L., Ying, Z., Hadam, J., Penrod, C.: Glutamate receptor mechanisms in human epileptic dysplastic cortex. Epilepsy Res. 32:24-33, 1998 https://doi.org/10.1016/S0920-1211(98)00037-0
  5. Baraban, S.C., Schwartzkroin, P.A.: Electrophysiology of CAl pyramidal neurons in an animal model of neuronal migration disorders: prenatal methylazoxymethanol treatment. Epilepsy Res. 22(2):145-156,1995 https://doi.org/10.1016/0920-1211(95)00045-3
  6. Baraban, S.C., Schwartzkroin, P.A.: Flurothyl seizure susceptibility in rats following prenatal methylazoxymethanol treatment. Epilepsy Res. 23: 189-194, 1996 https://doi.org/10.1016/0920-1211(95)00094-1
  7. Baraban, S.C., Wenzel, H.J., Hochman, D.W., Schwartzkroin, P.A.: Characterization of heterotopic cell clusters in the hippocampus of rats exposed to methylaxzoxymethanol in utero. Epilepsy Res. 39:87-102, 2000 https://doi.org/10.1016/S0920-1211(99)00104-7
  8. Barth, P.G.: Disorders of cerebral migration. Can. J. Neurol. Sci. 14:1-16, 1987 https://doi.org/10.1017/S031716710002610X
  9. Ben-Ari, Y.: Limbic seizure and brain damage produced by kainic acid: mechanisms and relevance to human temporal lobe epilepsy. Neuroscience 14(2):375-403,1985 https://doi.org/10.1016/0306-4522(85)90299-4
  10. Bruckner, C., Heinemann, U.: Effects of standard anticonvulsant drugs on different patterns of epileptiform discharges induced by 4-aminopyridine in combined entorhinal cortexhippocampal slices. Brain Res. 859: 15-20,2000 https://doi.org/10.1016/S0006-8993(99)02348-3
  11. Bruckner, C., Stenkamp, K., Meierkord, H., Heinemarm, U.: Epileptiform discharges induced by combined application of bicuculline and 4-aminopyridine are resistant to standard anticonvulsants in slices of rats. Neurosci. Lett. 268: 163165,1999 https://doi.org/10.1016/S0304-3940(99)00341-9
  12. Buckmaster, P.S., Schwarzkroin, P.A.: Hippocampal mossy cell function: a speculative view. Hippocampus 4(4):393402,1994 https://doi.org/10.1002/hipo.450040402
  13. Calcagnotto, M.E., Maredes, M.F., Baraban, S.C.: Heterotopic neurons with altered inhibitory synaptic function in an animal model of malformation-associated epilepsy. J. Neurosci. 22(17):7596-7605, 2002 https://doi.org/10.1523/JNEUROSCI.22-17-07596.2002
  14. Castro, P.A., Pleasure, S.J., Baraban, S.C.: Hippocampal heterotopia with molecular and electrophysiological properties of neocortical neurons. Neuroscience 114(4):961972, 2002 https://doi.org/10.1016/S0306-4522(02)00296-8
  15. Cavalheiro, E.A., Santos, N.F., Priel, M.R.: The pilocarpine model of epilepsy in mice. Epilepsia 37(10):1015-1019, 1996 https://doi.org/10.1111/j.1528-1157.1996.tb00541.x
  16. Chen, S., Hillman, D.E., Selective ablation of neurons by methylazoxymethanol during pre- and postnatal brain development. Exp. Neurol. 94:103-119,1986 https://doi.org/10.1016/0014-4886(86)90275-X
  17. Chevassus-au-Louis, N., Congar, P., Represa, A., Ben-Ari, Y., Gaiarsa, J.L.: Neuronal migration disorders: heterotopic neocortical neurons in CA1 provide a bridge between the hippocampus and the neocortex. Proc. Natl. Acad. Sci. 95(17): 1 0263-10268, 1998a
  18. Chevassus-au-Louis, N., Ben-Ari, Y., Vergnes, M.: Decreased seizure threshold and more rapid rate of kindling in rats with cortical malformation induced by prenatal treatment with methylazoxymethanol. Brain Res. 812:252-255, 1998b https://doi.org/10.1016/S0006-8993(98)00932-9
  19. Chadha, A., Howell, O., Atack, J.R., Sur, C., Duty, S.: Changes in (3H)zolpidem and (3H)Ro 15-1788 binding in rat globus pallidus and substantia nigra pars reticulata following a nigrostriatal tract lesion. Brain Res. 862(12):280-283, 2000 https://doi.org/10.1016/S0006-8993(00)02081-3
  20. Ciaroni, S., Cecchini, T., Gazzanelli, G., Grande, P.D.: Methylazoxymethanol (MAMac) effects on ontogenesis of the mouse neocortex. J. Hirrnforsch. 30:699-705, 1989
  21. Crestani, F., Low, K., Keist, R., Mandelli, M., Mohler, H., Rudolph, U.: Molecular targets for the myorelaxant action of diazepam. Mol. Pharmacol. 59(3):442-445, 2001 https://doi.org/10.1124/mol.59.3.442
  22. de Feo, M.R., Mecarelli, O., Ricci, C.F.: Seizure susceptibility in immature rats with micrencephaly induced by prenatal exposure to methylazoxymethanol acetate. Pharmacol. Res. 31:109-114,1995 https://doi.org/10.1016/1043-6618(95)80055-7
  23. Dudek, F.E., Spitz, M.: Hypothetical mechanisms for the cellular and neurophysiologic basis of secondary epileptogenesis: proposed role of synaptic reorganization. J. Clin. Neurophysiol. 14(2):90-101, Review 1997 https://doi.org/10.1097/00004691-199703000-00002
  24. Dudek, F.E.: Use of chronic epilepsy models in antiepileptic drug discovery: the effect of topiramate on spontaneous motor seizures in rats with kainate-induced epilepsy. Epilepsia 46(1):8-14,2005 https://doi.org/10.1111/j.0013-9580.2005.13404.x
  25. Duncan, J.S.: The promise of new antiepileptic drugs. Br. J. Clin. Pharmacol. 53(2):123-131, 2002 https://doi.org/10.1046/j.0306-5251.2001.01540.x
  26. Fleck, M.W., Hirotsune, S., Gambello, M.J., Phillips-Tansey, E., Suares, G., Mervis, R.F., Wynshaw-Boris, A., McBain, C.J.: Hippocampal abnormalities and enhanced excitability in a murine model of human lissencephaly. J. Neurosci. 20(7):2439-2450,2000 https://doi.org/10.1523/JNEUROSCI.20-07-02439.2000
  27. Fueta, Y., Avoli, M.: Effects of antiepileptic drugs on 4aminopyridine-induced epileptiform activitity in young and adult rat hippocampus. Epilepsy Res. 12: 207-215, 1992 https://doi.org/10.1016/0920-1211(92)90075-5
  28. Germano, I.M., Sperber, E.F.: The effects of neuronal migration disorders on seizure susceptibility. Epilepsia 35(Supp1.8): 137, 1994
  29. Germano, I.M., Sperber, E.F.: Increased seizure susceptibility in adult rats with neuronal migration disorders. Brain Res. 28:219-222, 1997
  30. Germano, I.M., Zhang, Y.F., Sperber, E.F., Moshe, S.L.: Neuronal migration disorders increase susceptibility to hyperthermia-induced seizures in developing rats. Epilepsia 37:902-910, 1996 https://doi.org/10.1111/j.1528-1157.1996.tb00044.x
  31. Glien, M., Brandt, C., Potschka, H., Loscher, W.: Effects of the novel anti epileptic drug levetiracetam on spontaneous recurrent seizures in the rat pilocarpine model of temporal lobe epilepsy. Epilepsia 43(4):350-357, 2002 https://doi.org/10.1046/j.1528-1157.2002.18101.x
  32. Hachad, H., Ragueneau-Majlessi, I., Levy, R.H.: New antiepileptic drugs: review on drug interactions. Ther. Drug. Monit. 24(1):91-103, 2002 https://doi.org/10.1097/00007691-200202000-00016
  33. Hellier, J.L., Patrylo, P.R., Buckmaster, P.S., Dudek, F.E.: Recurrent spontaneous motor seizures after repeated lowdose systemic treatment with kainate: assessment of a rat model of temporal lobe epilepsy. Epilepsy Res. 31(1):73-84, 1998 https://doi.org/10.1016/S0920-1211(98)00017-5
  34. Hirabayashi, S., Binnie, C.D., Janota, I., Polkey, C.E.: Surgical treatment of epilepsy due to cortical dysplasia: clinical and EEG findings. J. Neurol. Neurosurg. Psychiatry. 56:7650770, 1993 https://doi.org/10.1136/jnnp.56.7.765
  35. Houser, C.R.: Granule cell dispersion in the dentate gyrus of human with temporal lobe epilepsy. Brain Res. 535:195204, 1990 https://doi.org/10.1016/0006-8993(90)91601-C
  36. Kohno, T., Wakai, A., Ataka, T., Ikoma, M., Yamakura, T., Baba, H.: Actions of maidazolm on excitatory transmission in dorsal horn of adult rat spinal cord. Anesthesiology 104(2):338-343, 2006 https://doi.org/10.1097/00000542-200602000-00020
  37. Korpi, E.R., Grunder, G., Luddens, H.: Drug interactions at GABA(A) receptors. Prog. Neurobiol. 67(2):113-159, 2002
  38. Korpi, E.R., Kleingoor, C., Kettenmann, H., Seeburg, P.H.: Benzodiazepine-induced motor impairment linked to point mutation in cerebellar GABA(A) receptor. Nature 361(6410): 356-359, 1993 https://doi.org/10.1038/361356a0
  39. Loscher, W.: Animal models of epilepsy for the development of antiepileptogenic and disease-modifying drugs. A comparison of the pharmacology of kindling and post-status epilepticus models of temporal lobe epilepsy. Epilepsy Res. 50:105-123, 2002 https://doi.org/10.1016/S0920-1211(02)00073-6
  40. Loscher, W., Honack, D.: Profile of UCB L059, A novel anticonvulsant drug, in models of partial and generalized epilepsy in mice and rats. Eur. J. Pharmacol. 232:147-158, 1993 https://doi.org/10.1016/0014-2999(93)90768-D
  41. Mello, L.M., Cavalhiero, E.A., Tan, A.M.: Circuit mechanisms of seizures in the pilocarpine model of chronic epilepsy: cell loss and mossy fiber sprouting. Epilepsia 34:985-995, 1993 https://doi.org/10.1111/j.1528-1157.1993.tb02123.x
  42. Mikkelsen, J.D., Soderman, A., Kiss, A., Mirza, N.: Effects of benzodiazepines receptor agonists on the hypothalamicpituitary-adrenocortical axis. Eur. J. Pharmacol. 519(3):223230, 2005 https://doi.org/10.1016/j.ejphar.2005.06.049
  43. Mohler, H., Fritschy, J.M., Rudolph, U.: A new benzodiazepine pharmacology. J. Pharmacol. Exp. Ther. 300(1):2-8, Review, 2002 https://doi.org/10.1124/jpet.300.1.2
  44. Palmini, A., Andermann, F., Olivier, A., Tampieri, D., Robitaille, Y: Focal neuronal migration disorders and intractable partial epilepsy: results of surgical treatment. Ann. Neural. 30:750-757, 1991 https://doi.org/10.1002/ana.410300603
  45. Palmini, A.: Disorders of cortical development. Curr. Opin. Neurol.13:183-192, 2000 https://doi.org/10.1097/00019052-200004000-00012
  46. Prayson, R.A., Estes, M.L.: Cortical dysplasiz: a histopathologic study of 52 cases of partial lobectomy in patients with epilepsy. Hum. Pathol. 26:493-500,1995 https://doi.org/10.1016/0046-8177(95)90244-9
  47. Rudolph, U., Crestani, F., Mohler, H.: GABA(A) receptor subtypes: dissecting their pharmacological functions. Trends. Pharmacol. Sci. 22(4):188-194, 2001 https://doi.org/10.1016/S0165-6147(00)01646-1
  48. Sancini, G., Franceschetti, S., Battaglia, G., Colacitti, C., Di Luca, M., Spreafico, R., Avanzini, G.: Dysplastic neocortex and subcortical heterotopias in methylazoxymethanoltreated rats: an intracellular study of identified pyramidal neurones. Neurosci. Lett. 246(3):181-185,1998 https://doi.org/10.1016/S0304-3940(98)00258-4
  49. Smyth, M.D., Barbaro, N.M., Baraban, S.C.: Effects of antiepileptic drugs on induced epileptiform activity in a rat model of dysplasia. Epilepsy Res. 50:251-264, 2002 https://doi.org/10.1016/S0920-1211(02)00051-7
  50. Spreafico, R., Pasquier, B., Minotti, L., Garbelli, R., Kahane, P., Grand, S., Benabid, A., Tassi, L., Avanzini, G., Battaglia, G., Munari, C.: Immunocytochemical investigation on dysplastic human tissue from epileptic patients. Epilepsy Res. 32(1-2):32-48, 1998 https://doi.org/10.1016/S0920-1211(98)00034-5
  51. Stables, J.P., Bertram, E.H., White, H.S., Coulter, D.A., Dichter, M.A., Jacobs, M.P., Loscher, W., Lowenstein, D.H., Moshe, S.L., Noebels, J.L., Davis, M.: Models for epilepsy and epileptogenesis: report from the NIH workshop, Bethesda, Maryland. Epilepsia 43:1410-1420, 2002 https://doi.org/10.1046/j.1528-1157.2002.06702.x
  52. Wenzel, H.J., Robbins, C.A., Tsai, L.H., Schwartzkroin, P.A.: Abnormal morphological and functional organization of the hippocampus in a p35 mutant model of cortical dysplasia associated with spontaneous seizures. Neurosci. 21(3):983-998, 2001 https://doi.org/10.1523/JNEUROSCI.21-03-00983.2001
  53. White, H.S.: Preclinical development of antiepileptic drugs: past, present, and future directions. Epilepsia 44(suppl 7):28, 2003
  54. Xu, J.Y., Sastry, B.R., Benzodiazepine involvement in LTP of the GABA-ergic IPSC in rat hippocampal CA1 neurons. Brain Res. 1062(1-2): 134-143, 2005 https://doi.org/10.1016/j.brainres.2005.06.061
  55. Yamaguchi, S., Rogawski, M.A.: Effects of anticonvulsant drugs on 4-aminopyridine-induced seizures in mice. Epilepsy Res. 11 :9-16, 1992 https://doi.org/10.1016/0920-1211(92)90016-M