Evaluation of nigro-striatal pathway lesion in rats with genetic absence epilepsy during epileptogenesis in terms of immunohistochemical, behavioral and seizure parameters

Objective: Absence epilepsy is characterized by generalized seizures that occur at the end of a latent period called epileptogenesis. The mechanism of this epileptogenic process has not been elucidated yet. Although the importance of the basal ganglia in the development of epileptic seizures is well known, the role of nigrostriatal pathway in absence epilepsy has not been characterized yet. Specifically there is no experimental findings for the role of nigrostriatal pathway in absence epilepsy and its seizures. Consequently, in our study, the effects of nigrostriatal pathway degeneration in genetic absence epilepsy rats and non-epileptic Wistar animals were examined by immunohistochemical methods, electroencephalographic (EEG) recordings and behavioral experiments. Materials and Method: We used genetic absence epilepsy rats from Strasbourg (GAERS) and Wistar male rats in this study. When the animals were 30 days old, 6-Hydroxydopamine (6-OHDA) injection was applied to the medial forebrain region by the stereotaxic surgery to the experimental groups, and only mechanical application with a clean cannula to the sham-operated groups. Cylinder and apomorphine-induced rotation tests were performed on the 21st day of the surgical procedure. EEG recordings were taken from GAERS groups when they were 90 days old. Afterward, a 90-day-old naive animals was added as a control to all immunohistochemistry groups. The brains of the animals were removed by perfusion technique, and dopaminergic and GABAergic immunoreactivities in the striatum and substantia nigra (compact and reticulata) regions were evaluated by immunohistochemical methods. Results: In the rotation test, the number of contralateral rotation to the lesion in the GAERS and Wistar-6-OHDA groups were significantly higher than the GAERS and Wistar-sham-operated groups. As a result of the EEG, the cumulative duration and number of spike-and-wave discharges (SWDs) significantly increased in the GAERS-6-OHDA group when compared to the GAERS-sham-operative group. Also the result of the immunohistochemical experiments, a loss of dopaminergic activity was detected in both striatum and substantia nigra pars compacta, more prominent on the ipsilateral sides of the GAERS and Wistar-6-OHDA groups. Immunohistochemical examinations for GABAergic neurons, a decrease in the density of cells in the ipsilateral substantia nigra pars reticulata region was detected only in the GAERS-6-OHDA group. Conclusion: Our study is an original study in which the effect of nigrostriatal pathway degeneration on the development of seizures in a rat model with absence epilepsy during epileptogenesis was examined and the findings were compared with Wistar strain. The results obtained from our study constitute a step to elucidate the epileptogenesis mechanisms involved in the development of absence epilepsy.