Seizure-Induced Oxidative Stress in Temporal Lobe Epilepsy

Figure 4

Schematic representation of a synapse, with postsynaptic ionotropic glutamate receptors (NMDA, AMPA, and KA/GLUR6), its associated glial cells, and extrasynaptic effects of a seizure. First seizure due to hyperexcitability of neurons (as evident from increased Fos expression in the hippocampus) induces reactive gliosis at a later stage, which produces inflammatory cytokines and iNOS that are mediated by NFκB transcription. These in turn sensitize postsynaptic neurons and decrease their seizure threshold. Reactive astrocytes also downregulate glutamate uptake, thus increasing the concentration of glutamate at the synapse. These events contribute to further hyperexcitability of neurons as evident from increased spiking activity on EEG. These changes in turn lead to neurodegenerative changes after 3 days following the first seizure (Fluoro-Jade-B (FJB)+, neuronal nuclei protein (NeuN), the markers used to detect neurodegeneration) [30, 35, 87, 88].