title: Post-treatment of an NADPH oxidase inhibitor prevents seizure-induced neuronal death.
abstract: The present study sought to evaluate the neuroprotective effects of apocynin, an NADPH oxidase assembly inhibitor, on seizure-induced neuronal death. Apocynin, also known as acetovanillone, is a natural organic compound isolated from the root of Canadian hemp (Apocynum cannabium). It has been extensively studied to determine its disease-fighting capabilities and application in several brain insults, such as traumatic brain injury and stroke. Here we tested the hypothesis that post-treatment of apocynin may prevent seizure-induced neuronal death by suppression of NADPH oxidase-mediated superoxide production. Temporal lobe epilepsy (TLE) was induced by intraperitoneal injection of pilocarpine (25mg/kg) in male rats. Apocynin (30mg/kg, i.p.) was injected into the intraperitoneal space two hours after seizure onset. A second injection was performed 24h after seizure. To test whether apocynin inhibits NADPH oxidase activation-induced reactive oxygen species (ROS) production, dihydroethidium (dHEt, 5mg/kg, i.p.) was injected before onset of seizure and ROS production was detected five hours after seizure onset. Neuronal oxidative injury (4HNE), neuronal death (Fluoro Jade-B), blood brain barrier (BBB) disruption (IgG leak), neurotrophil infiltration (MPO) and microglia activation (CD11b) in the hippocampus was evaluated at three days after status epilepticus (SE). Pilocarpine-induced seizure increased p47 immunofluorescence in the plasma membrane of hippocampal neurons at 12h post-insult and apocynin treatment prevented this increase. The present study found that apocynin post-treatment decreased ROS production and lipid peroxidation after seizure and decreased the number of degenerating hippocampal neurons. Apocynin also reduced seizure-induced BBB disruption, neurotrophil infiltration and microglial activation. Taken together, the present results suggest that inhibition of NADPH oxidase by apocynin may have a high therapeutic potential to reduce seizure-induced neuronal dysfunction.
authors: Department of Physiology, Hallym University, College of Medicine, 1-Okcheon Dong, 39 Hallymdaehak-gil, Chuncheon 200-702, Republic of Korea.
authors: Jin Hee
authors: JH
authors: Kim
authors: Bong Geom
authors: BG
authors: Jang
authors: Bo Young
authors: BY
authors: Choi
authors: Hyeong Seop
authors: HS
authors: Kim
authors: Min
authors: M
authors: Sohn
authors: Tae Nyoung
authors: TN
authors: Chung
authors: Hui Chul
authors: HC
authors: Choi
authors: Hong Ki
authors: HK
authors: Song
authors: Sang Won
authors: SW
authors: Suh
mesh_terms: D000098:Acetophenones / Q000494:pharmacology*; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D003292:Convulsants / Q000633:toxicity; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010862:Pilocarpine / Q000633:toxicity; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000150:complications*
chemical_list: D000098:Acetophenones; D003292:Convulsants; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D010862:Pilocarpine; C056165:acetovanillone; D019255:NADPH Oxidases