title: Prevention of traumatic brain injury-induced neuronal death by inhibition of NADPH oxidase activation.
abstract: The present study aimed to evaluate the therapeutic potential of apocynin, an NADPH oxidase assembly inhibitor, on traumatic brain injury. Rat traumatic brain injury (TBI) was performed using a weight drop model. Apocynin (100mg/kg) was injected into the intraperitoneal space 15 min before TBI. Reactive oxygen species (ROS) in the hippocampal CA3 pyramidal neurons were detected by dihydroethidium (dHEt) at 3h after TBI. Oxidative injury was detected by 4-hydroxy-2-nonenal (4HNE) at 6h after TBI. Blood-brain barrier disruption was detected by IgG extravasation and neuronal death was evaluated with Fluoro Jade-B staining 24h after TBI. Microglia activation was detected by CD11b immunohistochemistry in the hippocampus at 1 week after TBI. ROS production was inhibited by apocynin administration in the hippocampal CA3 pyramidal neurons. This pre-treatment with apocynin decreased the blood-brain barrier disruption, the number of degenerating neurons in the hippocampal CA3 region and microglial activation after TBI. The present study indicates that apocynin pre-treatment prevents TBI-induced ROS production, thus decreasing BBB disruption, neuronal death and microglial activation. Therefore, the present study suggests that inhibition of NADPH oxidase by apocynin may have a high therapeutic potential to reduce traumatic brain injury-induced neuronal death.
authors.affiliation: Department of Physiology, Hallym University, College of Medicine, Chuncheon, South Korea.
authors.forename: Bo Yong
authors.initials: BY
authors.lastname: Choi
authors.forename: Bong Geom
authors.initials: BG
authors.lastname: Jang
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Kim
authors.forename: Bo Eun
authors.initials: BE
authors.lastname: Lee
authors.forename: Min
authors.initials: M
authors.lastname: Sohn
authors.forename: Hong Ki
authors.initials: HK
authors.lastname: Song
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Suh
mesh_terms: D000098:Acetophenones / Q000494:pharmacology*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D016923:Cell Death / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors*; D018696:Neuroprotective Agents / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000098:Acetophenones; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; C056165:acetovanillone; D019255:NADPH Oxidases