Nox2 and Nox4 Participate in ROS-Induced Neuronal Apoptosis and Brain Injury During Ischemia-Reperfusion in Rats.

Abstract

Previously studies have shown that Nox2 and Nox4, as members of nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase, Nox), participate in brain damage caused by ischemia-reperfusion (I/R). The aim of this study is to investigate the effects of specific chemical inhibitors of Nox2 and Nox4 on cerebral I/R-induced brain injury in rats. At 0.5h before MCAO surgery, the rats were pretreated with vehicle, Nox2 inhibitor (gp91ds-tat), and Nox4 inhibitor (GKT137831), respectively. After reperfusion for 24h, the infarct sizes of brain tissues in rats in various groups are determined. The penumbra (ischemic) tissues are collected to measure ROS levels, neuronal apoptosis, and degeneration, as well as the integrity of the blood-brain barrier (BBB) in brain tissues of rats. gp91ds-tat and GKT137831 pretreatment significantly reduced the infarct sizes in brain tissues of rats, effectively suppressed I/R-induced increase in ROS levels, neuronal apoptosis and degeneration, and obviously alleviated BBB damage. Under cerebral I/R conditions, Nox2 inhibitor (gp91ds-tat) and Nox4 inhibitor (GKT137831) can effectively play a protective role in the brain tissues of rats.