Diffuse brain injury (
DBI) is a leading cause of mortality and disability among young individuals and adults worldwide. In specific cases,
DBI is associated with permanent spatial learning dysfunction and motor deficits due to primary and secondary brain damage.
Nicotinamide adenine dinucleotide phosphate (
NADPH) oxidase (NOX) is a major complex that produces
reactive oxygen species (ROS) during the ischemic period. The complex aggravates brain damage and cell death following
ischemia/reperfusion injury; however, its role in
DBI remains unclear. The present study aimed to investigate the hypothesis that levels of NOX2 (a catalytic subunit of NOX)
protein expression and the activation of NOX are enhanced following
DBI induction in rats and are involved in aggravating secondary brain damage. A rat model of
DBI was created using a modified weight-drop device. Our results demonstrated that
NOX2 protein expression and NOX activity were enhanced in the CA1 subfield of the hippocampus at 48 and 72 h following
DBI induction. Treatment with
apocynin (50 mg/kg
body weight), a specific inhibitor of NOX, injected intraperitoneally 30 min prior to
DBI significantly attenuated
NOX2 protein expression and NOX activation. Moreover, treatment with
apocynin reduced
brain edema and improved spatial learning function assessed using the Morris water maze. These results reveal that treatment with
apocynin may provide a new neuroprotective therapeutic strategy against
DBI by diminishing the upregulation of
NOX2 protein and NOX activity.