Abstracts

Rationale: Increasing evidence implicates environmental influences as modulators of epileptogenesis. Environmental enrichment (EE), whereby laboratory animals are housed with running wheels, tunnels, and other stimulating objects, has been shown to be neuroprotective in several models of neurological disorders. Here we assessed whether EE affected epileptogenesis using the amygdala kindling model of acquired epilepsy, and the Genetic Absence Epilepsy Rats from Strasbourg (GAERS) model of genetic generalized epilepsy. Methods: At 3 weeks of age, male Wistar rats or GAERS were housed in either enriched (EE) or impoverished housing (IH) conditions, which were maintained for the duration of the study. For the kindling study, rats were implanted with a bipolar stimulating electrode into the left amygdala, and following recovery, were kindled twice daily. Seizure class (Racine scale) and duration were measured for each seizure until animals experienced 5 x Class V seizures, when they were deemed fully kindled. Afterdischarge threshold, and kindling rates were compared between EE and IH. For GAERS, at 8 weeks of age, rats were implanted with EEG recording electrodes, and underwent 24hour recordings each week until 20 weeks of age. Seizures were assessed offline using Spike-and-Wave Finder, and seizure frequency and duration compared over time between EE and IH. Results: In both models, EE induced an anti-epileptogenic effect. For kindling, EE increased the number of stimulations required to reach the different stages of kindling (p=0.05) but did not affect seizure threshold or duration (p>0.05). EE also reduced mossy fibre sprouting induced by kindling. In GAERS, EE delayed the onset of seizures, such that, at 9 weeks when the first recordings were performed, only 3 out of 8 rats had developed seizures, whereas in the IH group, all rats had seizures. As time progressed, the number of seizures experienced was less in the EE group, and at the end of the study (ie: 20 weeks) EE rats were having 50% less seizures than IH (p<0.001). No effect was observed on seizure duration. Conclusions: These studies show that environmental stimulation, in the form of enrichment, can retard the development of both acquired (kindling) and genetic (GAERS) forms of epilepsy. The fact that contrasting types of epilepsy are similarly influenced by enrichment may indicate that the mechanisms underlying this neuroprotection are common effects of the environment, and may be translatable to human epilepsy.