Article
Pathological and neurotransmitter receptor alterations in the mesial temporal lobe obtained during epilepsy surgery
Pathologische und Neurotransmitter-Rezeptor Alterationen in den mesialen Temporallappen gewonnen während der Epilepsiechirurgie
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Published: | May 8, 2019 |
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Objective: Neuropathological changes contribute to seizure-induced cell damage in different structures of the temporal lobe, including the hippocampus and the amygdala. Both cell injury and cell death in these brain regions play crucial roles in epileptogenesis in human brain. However, the mechanisms underlying cell damage and development of epilepsy in the temporal lobe have not been fully elucidated. The purpose of this study was to evaluate the correlation between the changes of major inhibitory and excitatory receptors and cell damage/death in the epileptic specimens.
Methods: The temporal lobe specimens of thirty-five patients with medically intractable epilepsy who have undergone epilepsy surgery were assessed for cell injury, cell death, and the expression of different inhibitory and excitatory receptors within different regions of the temporal lobe. Data obtained from epileptic tissues were compared to autopsy specimens. Immunohistochemical and quantitative RT-PCR methods were used to assess inhibitory and excitatory receptors.
Results: An increased rate of neuronal damage (dark cells) and apoptotic cells has been observed in different hippocampal and amygdala sub-regions compared to control tissues. Furthermore, our results revealed decreased expression levels of several GABAergic receptor subunits as well as GAD65 in specimens obtained during epilepsy surgery compared to control autopsy tissues. There was no statistical difference in the expression of glutamatergic excitatory receptor subunits between the epileptic and autopsy temporal lobe tissues. Enhancement of apoptotic cells was negatively correlated with the decreased expression of the investigated GABAergic receptor subunits and GAD65. There was no correlation between the cell injury and the expression of excitatory receptors in these brain regions.
Conclusion: The present data revealed the importance of inhibitory GABA-ergic neurotransmission in seizure-induced cell injury in patients with medically refractory temporal lobe epilepsy. This suggests the potential of some GABA receptor subunits as a target to prevent tissue damage and to control seizures in these patients.