A variety of animal models have been developed for the study of seizure disorders. However, there is a lack of direct, comparative data on the underlying nature of the seizure produced in these models. Knowledge regarding the similarities are differences among various seizure models would be of critical importance for determining what aspects of seizure mechanisms are being expressed in each of the models. The objective of this proposal is to compare directly three commonly used seizure models to determine the degree to which they share common seizure mechanisms. The models to be compared are kindling, maximal electroshock (MES) and pentylenetetrazol (PTZ). These models have been suggested to mimic aspects of partial complex, generalized idiopathic and absence seizures, respectively, and they have been extensively used for the development of clinically effective anticonvulsant drugs and for investigating mechanisms involved in epileptogenesis. These models will be compared within a defined, genetic framework using two genetically homogeneous mouse strains: DBA/2J (D2), a relatively seizure susceptible strain and C57BL/6J (B6), a relatively seizure resistant strain. The major foundation for this framework will be a set of recombinant inbred (RI) strains derived from B6 and D2 parents. The results of these experiments will define for each model a specific, genetically-determined, pattern of seizure susceptibility. Comparison of these model-specific patterns will provide a direct measure of the degree to which these models involve the same of different seizure mechanisms. This information will be of considerable value to our future approaches to defining seizure disorders and to our conceptualization of the epilepsies.
| Samoriski, G M; Piekut, D T; Applegate, C D (1998) Regional analysis of the spatial patterns of Fos induction in brain following flurothyl kindling. Neuroscience 84:1209-22 |
| Ferland, R J; Applegate, C D (1998) Decreased brainstem seizure thresholds and facilitated seizure propagation in mice exposed to repeated flurothyl-induced generalized forebrain seizures. Epilepsy Res 30:49-62 |
| Samoriski, G M; Piekut, D T; Applegate, C D (1997) Differential spatial patterns of Fos induction following generalized clonic and generalized tonic seizures. Exp Neurol 143:255-68 |
| Samoriski, G M; Applegate, C D (1997) Repeated generalized seizures induce time-dependent changes in the behavioral seizure response independent of continued seizure induction. J Neurosci 17:5581-90 |
