Inhibition of p38 MAPK Signaling Regulates the Expression of EAAT2 in the Brains of Epileptic Rats

: Seizures induce the release of excitatory amino acids (EAAs) from the intracellular fluid to the extracellular fluid, and the released EAAs primarily comprise glutamic acid (Glu) and asparaginic acid (Asp). Glu neurotransmission functions via EAA transporters (EAATs) to maintain low concentrations of Glu in the extracellular space and avoid excitotoxicity. EAAT2, the most abundant Glu transporter subtype in the central nervous system (CNS), plays a key role in the regulation of glutamate transmission. Previous studies have shown that SB203580 promotes EAAT2 expression by inhibiting the p38 mitogen-activated protein kinase (MAPK) signaling pathway, but whether SB203580 upregulates EAAT2 expression in epileptic rats is unknown. This study demonstrated that EAAT2 expression was increased in the brain tissue of epileptic rats. Intraperitoneal injection of a specific inhibitor of p38 MAPK, SB203580, reduced the time to the first epileptic seizure and attenuated the seizure severity. In addition, SB203580 treatment increased the EAAT2 expression levels in the brain tissue of epileptic rats. These results suggest that SB203580 could regulate epileptic seizures via EAAT2.