Midazolam contributes to neuroprotection against hypoxia/reoxygenation-induced brain injury in neonatal rats via regulation of EAAT2.

• EAAT2 expression in hippocampus reduced after H/R injury. • Midazolam alleviated H/R-induced apoptosis and learning and memory impairment. • Midazolam reversed the decreased expression of EAAT2 induced by H/R injury. • Involvement of EAAT2 in the neuroprotective effect of midazolam on H/R injury. Excitotoxicity is one of the main mechanisms related to hypoxia/reoxygenation (H/R) injury. Excitatory amino acid transporter (EAAT)2 mainly distributes on astrocytes and plays an important role on glutamate reuptake and glutamate homeostasis. Midazolam has a neuroprotective effect in some neuropathological conditions. The present study aimed to detect the role of EAAT2 in the neuroprotective effect of midazolam in neonatal rat brain subjected to H/R. Pretreatment with midazolam reversed H/R-induced apoptosis and downregulation of EAAT2 mRNA and protein expression in the hippocampus. Pretreatment with dihydrokainic acid (a selective inhibitor of EAAT2) exacerbated apoptosis, and thus inhibited the neuroprotective effect of midazolam against H/R injury. We demonstrated for the first time that dysregulation of EAAT2 expression may be related to the neural injury induced by H/R in rat pups, and pretreatment with midazolam attenuated apoptosis and improved learning and memory partly due to regulating EAAT2 expression. [ABSTRACT FROM AUTHOR]