GABAergic Network Alterations in Rat Models of Acquired Epilepsy

s s i g n i f i c a n t e c o n o m i c i m p l i c a t i o n s .A n t i -e p i l e p t i c d r u g s c a n a c h i e v e a successful outcome in about 70% of epilepsy patients, but, unfortunately, there is no treatment to prevent or modify disease development before seizure onset in patients at known risk.The published data from studies investigating animal models of the acquired epilepsy suggests that in adult brain, the changes in the GABAergic network in post-injury brain play a major role in epileptogenesis.However, it is still uncertain whether data obtained from one of the animal models can be extrapolated to others.The aim of this thesis study was to profile and compare alterations in the GABAergic network after traumatic brain injury (TBI) and status epilepticus (SE).A special emphasis was placed on assessing a reduction in the number of the inhibitory interneurons in the hippocampus and in the reticular nucleus of the thalamus (RT) in rats whose epilepsy phenotype was studied.Moreover, TBI induced plasticity was studied in ventral posterior medial (VPM) and lateral (VPM) nuclei of the thalamus.Finally, the quantitative RT-PCR array was used to investigate if the loss of presynaptic inputs changed the gene expression of the GABAA receptor subunits.The results indicated that the loss of GABAergic interneurons in the dentate gyrus and hippocampus proper was clearly greater and more widespread in rats with TBI with no spontaneous seizures during two weeks of video-EEG monitoring at 6 months post-injury than in rats that developed epilepsy after SE.Moreover, there was a clear decrease in the nu mber of par v al bu min posi tiv e n eu r ons b i l ater al ly in th e RT a t 6 m on th s after T BI.Furthermore, a robust increase was found in the intensity of PARV-ir axonal labeling in the lateral aspects of the ipsilateral VPM-VPL.Unlike the situation in controls, there were no correlations between the seizure susceptibility and density of parvalbumin immunoreactivity in the RT or VPM-VPL after TBI.Relatively few changes in the expression GABAA receptor subunits were found at 6 months post-TBI.In conclusion, the present unbiased quantification of different interneuron classes in wellphenotyped animals challenges the previous concept that the more severe the loss of hippocampal interneurons, the more severe will be the epilepsy.Furthermore, it provided new information on the role of post-traumatic molecular and cellular alterations in the GABAergic network in the hippocampus and thalamus.