NADPH oxidase inhibition improves neurological outcome in experimental traumatic brain injury

• The nox2 protein was increased with two peaks after TBI.
• Pre-treatment with the apocynin markedly inhibited nox2 protein expression.
• Apocynin attenuated MDA level and TBI-induced blood–brain barrier dysfunction.
• Apocynin attenuated TBI-induced neurological deficit and cortical apoptosis.

PurposeTraumatic brain injury (TBI) is a worldwide health problem with oxidative stress recognized as a major pathogenetic factor. The present experimental study was designed to explore the neuroprotective effect of NADPH oxidase (NOX) inhibitor, apocynin, on mouse TBI.MethodsModerately severe weight-drop impact head injury was induced in adult male mice, randomly divided into four groups: sham, TBI, TBI + vehicle and TBI + apocynin treatment. Apocynin (50 mg/kg) was injected intraperitoneally 30 min before TBI. The expression of NOX2 protein was investigated using immunoblotting techniques 1 and 24 h after TBI. Neurological score was evaluated 24 h after TBI. Blood–brain barrier disruption was detected by Evans blue extravasation and cortical apoptosis was analyzed by TUNEL assay. Additionally, we assessed tissue levels of malondialdehyde (MDA).ResultsNOX2 expression increased rapidly following TBI in male mice, with an early peak at 1 h, followed by a second peak at 24 h. Pre-treatment with the NOX inhibitor, apocynin markedly inhibited NOX2 expression. Apocynin also attenuated MDA levels and TBI-induced blood–brain barrier dysfunction. In addition apocynin significantly attenuated TBI-induced neurological deficits and cortical apoptosis.ConclusionPre-treatment with apocynin effectively attenuates markers of cerebral oxidative stress after TBI, thus supporting the hypothesis that apocynin is a potential neuroprotectant and adjunct therapy for TBI patients.