Seizure-Induced Oxidative Stress in Temporal Lobe Epilepsy

Figure 2

Post-SE pathways in neurodegeneration. SE increases glutamate receptors subunits interactions (NMDA, AMPA, and metabotropic), receptor turn-over, and their trafficking to the postsynaptic membrane. This leads to rapid calcium influx and calcium overload. As a result of this, several calcium dependent enzymes get activated in uncontrolled manner. This results in the activation of several signaling pathways that causes mitochondrial swelling, decrease in ATP, and increase in ROS, which results in oxidization of protein, lipid, and DNA, causing neuronal death. In addition, hypermetabolism, overwhelming glycolysis, and TCA cycle during SE further increase ROS/RNS. High production of lactate can cause cerebral lactic acidosis thereby increasing the production of ROS causing further damage due to mitochondrial dysfunction. Excessive calcium and ROS leads to the collapse of mitochondrial membrane potential, activation of mitochondrial matrix enzymes, and opening of mitochondrial permeability transition pores, decreasing ATP production. ROS are produced in mitochondria through the activity of ETC as a by-product of oxidative phosphorylation. CoASH/CoASSG and GSH/GSSG (described in Figure 3) ratio also decrease in brain tissues during this process and following SE, due to increased oxidative stress [44, 81–84]. TCA: tricarboxylic acid cycle; ETC: electron transport chain; mtDNA: mitochondrial DNA; Cyt C NAD: cytochrome NADH reductase; CoASH: coenzyme A; CoASSG: coenzyme A glutathione disulfide; SE: status epilepticus.