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Characteristics of a primate model of focal motor cortical seizures suitable for preclinical testing of therapies like DBS

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DOI: 10.4236/wjns.2014.41006    3,537 Downloads   5,399 Views   Citations


Background and objective: Generating and characterizing primate models of epileptic seizures are important for understanding pathophysiology of diseases and establishing preclinical efficacy of novel therapies like Deep Brain Stimulation. A focal motor epilepsy model is described here. Method: Seizures were obtained after intracortical penicillin injection into the motor strip through a cannula in two awake monkeys and electrocorticograms were recorded by epidural screws. Seizures were analyzed and compared for number, average duration of each seizure and total duration of ictal activity. Pharmaco-resistance for antiepileptic drug was tested by administration of Diazepam during seizures. Results: A motor status with seizures mimicking those seen in Kojevnikov’s syndrome was easily generated several minutes after penicillin injection and lasted 24 h on an average. The model thus characterized appears stable and consistent. There is no significant variation between experiments in individual primate as well as between two specimens. Diazepam though reduced the total duration of seizures, failed to abolish behavioural seizures. Conclusion: This model represents a good alternative model for preclinical research aiming at testing novel therapies because seizures are obtained on demand, last up to 24 h after a single penicillin injection, are stable and resistant to Diazepam.

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The authors declare no conflicts of interest.

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Prabhu, S. , Piallat, B. , Devergnas, A. , Blauwblomme, T. , Sherdil, A. , Chivoret, N. , David, O. and Chabardès, S. (2014) Characteristics of a primate model of focal motor cortical seizures suitable for preclinical testing of therapies like DBS. World Journal of Neuroscience, 4, 47-57. doi: 10.4236/wjns.2014.41006.


[1] Jobst, B. (2010) Brain stimulation for surgical epilepsy. Epilepsy Research 8, 154-161.
[2] Rogawski, M.A. (2009) Convection-enhanced delivery in the treatment of epilepsy: Nontraditional epilepsy treatment approaches. Neurotherapeutics, 6, 344-351.
[3] Rothman, S.M., Matthew, D., Smyth, M.D., Yang, X.-F. and Peterson, G.P. (2005) Focal cooling for epilepsy: An alternative therapy that might actually work. Epilepsy & Behavior, 7, 214-221.
[4] Chabardes, S., Najm, L. and Luders, H. (2008) Animal models of epilepsy relevant for epilepsy surgery studies. In: Luders, H. Ed., Handbook of Epilepsy Surgery, Infroma Healthcare, London, 1405-1413
[5] Pallud, J., Devergnas, A., Chabardes, S. and Depaulis, A. (2008) Animal models to develop surgery of focal epilepsies? Neurochirurgie, 54,128-134.
[6] Chevassus-au-Louis, N., Baraban, S.C., Gaiarsa, J.L. and Ben-Ari, Y. (1999) Cortical malformations and epi-lepsy: New insights from animal models. Epilepsia, 40, 811-821.
[7] De Deyn, P.P. and D’Hooge, R. (1999) Animal models of focal epilepsy. Acta Neurologica Belgica, 99, 222-225.
[8] Fisher, R.S. (1989) Animal models of the epilepsies. Brain Research—Brain Research Reviews 14, 245-278.
[9] Hashizume, K. and Tanaka, T. (1998) Multiple subpial transection in kainic acid-induced focal cortical seizure. Epilepsy Research, 32, 389-399.
[10] Yamamoto, K., Tanaka, T. and Yonemasu, Y. (1995) Jacksonian seizure model induced by a kainic acid mi-croinjection into unilateral sensori-motor cortex. Brain & Nerve, 47, 477-483.
[11] Yang, X.F., Duffy, D.W., Morley, R.E. and Roth-man, S.M. (2002) Neocortical seizure termination by focal cooling: Temperature dependence and automated seizure detection. Epilepsia, 43, 240-245.
[12] Willmore, L.J., Sypert, G.W., Munson, J.V. and Hurd, R.W. (1978) Chronic focal epileptiform discharges induced by injection of iron into rat and cat cortex. Science 200, 1501-1503.
[13] Eder, H.G., Jones, D.B. and Fisher, R.S. (1997) Local perfusion of diazepam attenuates interictal and ictal events in the bicuculline model of epilepsy in rats. Epilepsia, 38, 516-521.
[14] Stein, A.G., Eder, H.G., Blum, D.E., Drachev, A. and Fisher, R.S. (2000) An automated drug delivery system for focal epilepsy. Epilepsy Research, 39, 103-114.
[15] Johnson, H., et al. (1946) Effects of antibiotic sub-stances on the central nervous system. Archives of Neurology & Psychiatry, 56, 184-197.
[16] Elger, C.E. and Speckmann, E.J. (1983) Penicil-lin-induced epileptic foci in the motor cortex: Vertical inhibition. Electroencephalography & Clinical Neuro-physiology, 56, 604-622.
[17] Gloor, P. (1969) Epileptogenic action of penicillin. Annals of the New York Academy of Sciences, 166, 350-360.
[18] Gloor, P., Quesney, L.F. and Zumstein, H. (1977) Pathophysiology of generalized penicillin epilepsy in the cat: the role of cortical and subcortical structures. II. Topical application of penicillin to the cerebral cortex and to subcortical structures. Electroencephalography & Clinical Neurophysiology, 43, 79-94.
[19] Matsumato, H. and Ajmonemarsan, C. (1964) Cellular mechanism in experimental epileptic seizure. Science, 144, 193-194.
[20] Meyer, H. and Prince, D. (1973) Convulsant actions of penicillin: Effects on inhibitory mechanisms. Brain Research, 53, 477-482.
[21] Noebels, J.L. and Prince, D.A. (1977) Presynaptic origin of penicillin after discharges at mammalian nerve terminals. Brain Research, 138, 59-74.
[22] Anschel, D.J., Ortega, E. and Fischer, R.S. (2004) Diazepam prophylaxis for bicuculline-induced seizures: A rat dose-response model. Neurosciences Letters, 356, 66-68.
[23] Campbell, A.M. and Holmes, O. (1984) Bicuculline epileptogenesis in the rat. Brain Research, 323, 239-246.
[24] Ajmone-Marsan, C. (1972) Focal electrical stimula-tion. In: Purpura, D.P., Penry, J.K., Tower D.B. and Woodburry, D. Eds., Experimental Models of Epilepsy—A Manual for the Laboratory Worker, Raven Press, New York, 147-172.
[25] Hiroshi, S., Najm, I., Boongird, A., Nair, D., Burrier, C. and Luders, H.O. (2002) High-frequency direct cortical stimulation and its production of after discharges. Epilepsia, 43.
[26] Le Van Quyen, M., lachaux, J., Rodriguez, E., Lutz, A., et al. (2001) Journal of Neurosciences Methods, 111, 8398.
[27] Pockberger H, Rappelsberger, P. and Petsche, H. (1984) Penicillin-induced epileptic phenomena in the rabbit’s neocortex I. The development of interictal spikes after epicortical application of penicillin. Brain Research, 309, 241-246.
[28] Opdam, H.I., Federico, P., Jackson, G.D., Bu-chanan, J., Abbott, D.F., Fabinyi, G.C., Syngeniotis, A., Vosmansky, M., Archer, J.S., Wellard, R.M. and Bel-lomo, R. (2002) A sheep model for the study of focal epilepsy with concurrent intracranial EEG and functional MRI. Epilepsia, 43, 779-787.
[29] Kato, M., Malamut, B.L., Caveness, W.F., et al. (1980) Local cerebral glucose utilization in newborn and pubescent monkeys during focal motor seizures. Annals of Neurology, 7, 204-212.
[30] Gale, K. (2004) The nigral control of epilepsy: Basal ganglia circuitry as a substrate for seizure control In: Luders, H.O., Ed., Deep Brain Stimulation and Epilepsy 1st Ed Martin Duniz, London and New York, pp. 87-96.
[31] Obeso, J.A., Rothwell, J.C. and Marsden, C.D. (1985) The spectrum of cortical myoclonus. From focal reflex jerks to spontaneous motor epilepsy. Brain, 108 (Pt 1), 193-124.
[32] Bencaud, J., Boris. A. and Trottier, S. (1982) Continuous partial epilepsy: Syndrome and diseases. Revue Neurologique (Paris), 138, 803-814.
[33] Shomer, D.L. (1993) Focal status epilepticus and epilepsia partialis continua in adults and children. Epilepsia, 34, S29-S36.
[34] Mazarati, A.M. and Wasterlain, C.G. (1997) Blockers of NMDA receptor restore paired-pulse inhibition in the rat dentate gyrus lesioned by perforant path stimulation. Neuroscience Letters, 234, 135-138.
[35] Spellman, T., Peterchev, A. and Lisanby, S. (2009) Focal electrically administered seizure therapy: A novel form of ECT illustrates the roles of current directionality, polarity, and electrode configuration in seizure induction. Neuropsychopharmacologym, 34, 2002-2010.

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