Hostname: page-component-848d4c4894-pjpqr Total loading time: 0 Render date: 2024-07-05T22:28:50.042Z Has data issue: false hasContentIssue false
  • English
  • Français

A Spontaneous Recurrent Seizure Bioassay for Anti-Epileptogenic Molecules

Published online by Cambridge University Press:  02 December 2014

Angela P. Lyon ,
Dan Wainman ,
Sandra Marone  and
Donald F. Weaver
Angela P. Lyon
Affiliation:
Department of Chemistry, Queen’s University, Kingston, Ontario, Canada
Dan Wainman
Affiliation:
Department of Chemistry, Queen’s University, Kingston, Ontario, Canada
Sandra Marone
Affiliation:
Department of Chemistry, Queen’s University, Kingston, Ontario, Canada
Donald F. Weaver
Affiliation:
Departments of Chemistry and Medicine (Neurology), School of Biomedical Engineering, Dalhousie University, Halifax, Nova Scotia, Canada
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Drug design in epilepsy is now tackling a new target - epileptogenesis. This is the process whereby a normal brain becomes susceptible to recurrent seizures. One of the stumbling blocks in the design and discovery of new chemical entities as antiepileptogenics is the implementation of an appropriate biological model. Current models, such as the maximal electroshock model, are models of seizures, not models of epileptogenesis. To develop such a model, we have extended and modified a chronic pilocarpine spontaneous recurrent seizure (SRS) model for the purposes of developing a bioassay with which to screen new compounds for putative antiepileptogenic bioactivity.

La conception de médicaments antiépileptiques s’attaque maintenant à une nouvelle cible -l’épileptogenèse, le processus par lequel un cerveau normal devient sujet à des crises àpileptiques ràcurrentes. Une des pierres d’achoppement dans la conception et la dàcouverte de nouveaux produits chimiques antiàpileptogènes est la mise au point d’un modèle biologique approprià. Les modèles actuels comme le modèle d’àlectrochoc maximal sont des modèles de crises àpileptiques et non pas des modèles d’àpileptogenèse. Afin de dàvelopper un tel modèle, nous avons àlargi et modifià un modèle de crises convulsives ràcurrentes spontanàes en ràponse à l’administration de pilocarpine dans le but de dàvelopper un bioessai pour àvaluer l’actività antiàpileptogène de nouveaux composàs.

Type
Experimental Neurosciences
Information
Canadian Journal of Neurological Sciences , Volume 32 , Issue 1 , February 2005 , pp. 97 - 102
Copyright
Copyright © The Canadian Journal of Neurological 2014

References

1. Lothman, EW. Neurobiology as a basis for rational polypharmacy. Epilepsy Res 1996; (Suppl 11): 3–7.Google ScholarPubMed
2. Weaver, DF. Epileptogenesis, ictogenesis and the design of futureantiepileptic drugs. Can J Neurol Sci 2003; 30: 4–7.Google Scholar
3. Young, B, Rapp, RP, Norton, JA, et al. Failure of prophylacticallyadministered phenytoin to prevent late posttraumatic seizures. J Neurosurg 1983; 58(2): 236–241.Google Scholar
4. Glotzner, FL, Haubitz, I, Miltner, F, Kapp, G, Pflughaupt, KW. Seizureprevention using carbamazepine following severe brain injuries. Neurochirurgia 1983; 26(3): 66–79.Google Scholar
5. Pitkanen, A. Drug-mediated neuroprotection and antiepilepto-genesis. Neurology 2002; 59 (Suppl 5): S27-S33.Google Scholar
6. Pitkanen, A. Efficacyof current antiepileptics to preventneurodegeneration in epilepsy models. Epilepsy Res 2002; 50: 141–160.Google Scholar
7. Girgis, M. Kindling as a model of limbic epilepsy. Neuroscience 1981; 6: 1695–1706.Google Scholar
8. Goldensohn, ES. The relevance of secondary epileptogenesis to thetreatment of epilepsy: kindling and the mirror focus. Epilepsia 1984; 25 (Suppl 2): S156-S168.Google Scholar
9. Mello, LEAM, Cavalheiro, EA, Tan, AM, et al. Molecularneurobiology of epilepsy. Epilepsy Res 1992; (Suppl 9): 51–60.Google Scholar
10. Lothman, EW. The biochemical basis and pathophysiology of statusepilepticus. Neurology 1990; 40 (Suppl 2): 13–23.Google Scholar
11. Sloviter, RS. A simplified Timm stain procedure compatible withformaldehyde fixation and routine paraffin embedding of ratbrain. Brain Res Bull 1982; 8: 771–774.Google Scholar
12. Mello, LEAM, Cavalheiro, EA, Tan, AM, et al. Circuit mechanismsof seizures in the pilocarpine model of chronic epilepsy: cell loss and mossy fibre sprouting. Epilepsia 1993; 34(6): 985–995.Google Scholar
13. Liu, Z, Nagaro, T, Desjardins, GC, Gloor, P, Avoli, M. Quantitativeevaluation of neuronal loss in the dorsal hippocampus of rats with long-term pilocarpine seizures. Epilepsy Res 1994; 17: 237–247.Google Scholar
14. Poirier, JL, Capek, R, De Koninck, Y. Differential progression of darkneuron and fluoro-jade labeling in the rat hippocampus following pilocarpine-induced status epilepticus. Neuroscience 2000; 97(1): 59–68.Google Scholar
15. Coulter, DA, Rafiq, A, Shumate, M, et al. Brain injury-inducedenhanced limbic epileptogenesis: anatomical and physiological parallels to an animal model of temporal lobe epilepsy. Epilepsy Res 1996; 26: 81–91.Google Scholar
16. Lynch, M, Sayin, U, Golarai, G, Sutula, T. NMDA receptor-dependentplasticity of granule cell spiking in the dentate gyrus of normaland epileptic rats. J Neurophysiol 2000; 84(6): 2868–2879.Google Scholar
17. Bekenstein, JW, Lothman, EW. Dormancy of inhibitory interneuronsin a model of temporal lobe epilepsy. Science 1993; 259(5091): 97–100.Google Scholar
18. Houser, AR, Esclapez, M. Vulnerability and plasticity of the GABA system in the pilocarpine model of spontaneous recurrent seizures. Epilepsy Res 1996; 26: 207–218.Google Scholar
19. Rice, AC, DeLorenzo, RJ. NMDA receptor activation during statusepilepticus is required for the development of epilepsy. Brain Res 1998; 782: 240–247.Google Scholar
20. Sloviter, R. Permanently altered hippocampal structure, excitability,and inhibition after experimental status epilepticus in the rat: the dormant basket cell hypothesis and its possible relevance to temporal lobe epilepsy. Hippocampus 1991; 1: 41–66.Google Scholar
20. Falch, E, Hedegaard, A. Competitive stereostructure-activity studieson GABAA and GABAB receptor sites and GABA uptake using rat brain membrane preparations. J Neurochem 1986; 47(3): 898–903.CrossRefGoogle Scholar
21. Baron, BM, Harrison, BL, Kehne, JH, et al. Pharmacologicalcharacterization of MDL-105.519 an NMDA receptor glycine siteantagonist. Eur J Pharmacol 1997; 323: 181–192.Google Scholar
22. Adams, B, Sazgar, M, Osehobo, P, et al. Nerve growth factoraccelerates seizure development, enhances mossy fiber sprouting, and attenuates seizure-induced decreases in neuronal density in the kindling model of epilepsy. J Neurosci 1997; 17(14): 5288–5296.Google Scholar
23. Racine, RJ. Modification of seizure activity by electrical stimulation.ii. motor seizure. Electroencephalogr Clin Neurophysiol 1972; 32: 281–294.Google Scholar
24. White, HS. Animal models of epileptogenesis. Neurology 2002; 59(Suppl 5): S7-S14.CrossRefGoogle ScholarPubMed