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Neurochemistry of Epilepsy 

Neurochemistry of Epilepsy
Neurochemistry of Epilepsy

B. Keith Day

, Lawrence Eisenman

, and R. Edward Hogan

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date: 02 July 2022

Epileptic seizures in the human brain are largely driven by neurochemical changes. The hypothesis that seizures arise from an imbalance in excitation and inhibition in the brain refers to an alteration in the balance between the major corresponding neurotransmitter systems, glutamate and γ-aminobutyric acid (GABA), respectively. Both have complex synthesis, release, receptor activation, uptake, and repletion all of which may have significant roles in the pathophysiological neuronal excitability underlying epilepsy, and are prominently involved in the neuroanatomical structures that tend to be epileptogenic. Many animal models manipulate these systems to produce seizures for neurochemical studies that provide support for the importance of glutamate and GABA in epilepsy. Human microdialysis studies have shown dynamic changes in glutamate and GABA before and during seizures and inspired the use of other technologies to complement these findings. The roles of the other major neurotransmitter systems in epilepsy are also reviewed. Finally, the neurochemistry of epilepsy provides a basis for antiepileptic drug efficacy, rational drug design, and rational polypharmacy. However, we also provide an example where clinical experience with applying these lessons produced unexpected results, showing that the complexities of epilepsy and its treatment continues to intrigue and inspire us to continue further investigations.

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