title: Attenuation of brain edema and spatial learning deﬁcits by the inhibition of NADPH oxidase activity using apocynin following diffuse traumatic brain injury in rats.
abstract: 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.
authors.affiliation: Department of Surgery, Hebei Medical University, Shijiazhuang 050017, PR China.
authors.forename: Si-Xin
authors.initials: SX
authors.lastname: Song
authors.forename: Jun-Ling
authors.initials: JL
authors.lastname: Gao
authors.forename: Kai-Jie
authors.initials: KJ
authors.lastname: Wang
authors.forename: Ran
authors.initials: R
authors.lastname: Li
authors.forename: Yan-Xia
authors.initials: YX
authors.lastname: Tian
authors.forename: Jian-Qiang
authors.initials: JQ
authors.lastname: Wei
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Cui
mesh_terms: D000098:Acetophenones / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001929:Brain Edema / Q000188:drug therapy / Q000201:enzymology / Q000209:etiology*; D001930:Brain Injuries / Q000150:complications*; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D007859:Learning Disabilities / Q000188:drug therapy / Q000201:enzymology / Q000209:etiology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000378:metabolism; D008568:Memory / Q000187:drug effects; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats
chemical_list: D000098:Acetophenones; D008562:Membrane Glycoproteins; C056165:acetovanillone; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases