Strain differences affect the induction of status epilepticus and seizure-induced morphological changes

Genetic deficits have been discovered in human epilepsy, which lead to alteration of the balance between excitation and inhibition, and ultimately result in seizures. Rodents show similar genetic determinants of seizure induction. To test whether seizure-prone phenotypes exhibit increased seizure-related morphological changes, we compared two standard rat strains (Long-Evans hooded and Wistar) and two specially bred strains following status epilepticus. The special strains, namely the kindling-prone (FAST) and kindling-resistant (SLOW) strains, were selectively bred based on their amygdala kindling rate. Although the Wistar and Long-Evans hooded strains experienced similar amounts of seizure activity, Wistar rats showed greater mossy fiber sprouting and hilar neuronal loss than Long-Evans hooded rats. The mossy fiber system was affected differently in FAST and SLOW rats. FAST animals showed more mossy fiber granules in the naive state, but were more resistant to seizure-induced mossy fiber sprouting than SLOW rats. These properties of the FAST strain are consistent with those observed in juvenile animals, further supporting the hypothesis that the FAST strain shares circuit properties similar to those seen in immature animals. Furthermore, the extent of mossy fiber sprouting was not well correlated with sensitivity to status epilepticus, but was positively correlated with the frequency of spontaneous recurrent seizures in the FAST rats only, suggesting a possible role for axonal sprouting in the development of spontaneous seizures in these animals. We conclude that genetic factors clearly affect seizure development and related morphological changes in both standard laboratory strains and the selectively bred seizure-prone and seizure-resistant strains.