title: NADPH oxidase inhibition improves neurological outcome in experimental traumatic brain injury.
abstract: OBJECTIVE
  Traumatic 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.
  
  
  METHODS
  Moderately 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 24h after TBI. Neurological score was evaluated 24h 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).
  
  
  RESULTS
  NOX2 expression increased rapidly following TBI in male mice, with an early peak at 1h, followed by a second peak at 24h. 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.
  
  
  CONCLUSIONS
  Pre-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.
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China; Department of Neurosurgery, People's Hospital Affiliated to Jiangsu University, Zhenjiang, Jiangsu Province, China.
authors.forename: Xin-Yu
authors.initials: XY
authors.lastname: Lu
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China. Electronic address: njhdwang@hotmail.com.
authors.forename: Han-Dong
authors.initials: HD
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Ding
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
mesh_terms: D000098:Acetophenones / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008813:Mice, Inbred ICR; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*
chemical_list: D000098:Acetophenones; D000975:Antioxidants; D018696:Neuroprotective Agents; D008315:Malondialdehyde; C056165:acetovanillone; D019255:NADPH Oxidases
keywords: Apocynin; NADPH oxidase; NOX2; Traumatic brain injury