title: Inhibition of NADPH oxidase activation reduces EAE-induced white matter damage in mice.
abstract: BACKGROUND
  To evaluate the role of NADPH oxidase-mediated reactive oxygen species (ROS) production in multiple sclerosis pathogenesis, we examined the effects of apocynin, an NADPH oxidase assembly inhibitor, on experimental autoimmune encephalomyelitis (EAE).
  
  
  METHODS
  EAE was induced by immunization with myelin oligodendrocyte glycoprotein (MOG (35-55)) in C57BL/6 female mice. Three weeks after initial immunization, the mice were analyzed for demyelination, immune cell infiltration, and ROS production. Apocynin (30 mg/kg) was given orally once daily for the entire experimental course or after the typical onset of clinical symptom (15 days after first MOG injection).
  
  
  RESULTS
  Clinical signs of EAE first appeared on day 11 and reached a peak level on day 19 after the initial immunization. The daily clinical symptoms of EAE mice were profoundly reduced by apocynin. The apocynin-mediated inhibition of the clinical course of EAE was accompanied by suppression of demyelination, reduced infiltration by encephalitogenic immune cells including CD4, CD8, CD20, and F4/80-positive cells. Apocynin reduced MOG-induced pro-inflammatory cytokines in cultured microglia. Apocynin also remarkably inhibited EAE-associated ROS production and blood-brain barrier (BBB) disruption. Furthermore, the present study found that post-treatment with apocynin also reduced the clinical course of EAE and spinal cord demyelination.
  
  
  CONCLUSIONS
  These results demonstrate that apocynin inhibits the clinical features and neuropathological changes associated with EAE. Therefore, the present study suggests that inhibition of NADPH oxidase activation by apocynin may have a high therapeutic potential for treatment of multiple sclerosis pathogenesis.
authors.affiliation: Department of Physiology, College of Medicine, Hallym University, Chuncheon, South Korea. bychoi@hallym.ac.kr.
authors.forename: Bo Young
authors.initials: BY
authors.lastname: Choi
authors.affiliation: Department of Physiology, College of Medicine, Hallym University, Chuncheon, South Korea. fate0710@hallym.ac.kr.
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Physiology, College of Medicine, Hallym University, Chuncheon, South Korea. rnlduadkfk136@hallym.ac.kr.
authors.forename: A Ra
authors.initials: AR
authors.lastname: Kho
authors.affiliation: Department of Physiology, College of Medicine, Hallym University, Chuncheon, South Korea. inyeol@hallym.ac.kr.
authors.forename: In Yeol
authors.initials: IY
authors.lastname: Kim
authors.affiliation: Department of Physiology, College of Medicine, Hallym University, Chuncheon, South Korea. sshlee@hallym.ac.kr.
authors.forename: Song Hee
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Physiology, College of Medicine, Hallym University, Chuncheon, South Korea. supsock1126@naver.com.
authors.forename: Bo Eun
authors.initials: BE
authors.lastname: Lee
authors.affiliation: Chuncheon Sacred Heart Hospital, Department of Rehabilitation Medicine, College of Medicine, Hallym University, Chuncheon, South Korea. choi.eunhi@gmail.com.
authors.forename: Eunhi
authors.initials: E
authors.lastname: Choi
authors.affiliation: Department of Nursing, Inha University, Incheon, South Korea. sohnmin@inha.ac.kr.
authors.forename: Min
authors.initials: M
authors.lastname: Sohn
authors.affiliation: Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Canada. Mackenzie.Stevenson@umanitoba.ca.
authors.forename: Mackenzie
authors.initials: M
authors.lastname: Stevenson
authors.affiliation: CHA Bundang Medical Center, School of Medicine, CHA University, Kyunggi do, South Korea. hendrix74@cha.ac.kr.
authors.forename: Tae Nyoung
authors.initials: TN
authors.lastname: Chung
authors.affiliation: Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Canada. Tiina.Kauppinen@med.umanitoba.ca.
authors.forename: Tiina M
authors.initials: TM
authors.lastname: Kauppinen
authors.affiliation: Department of Physiology, College of Medicine, Hallym University, Chuncheon, South Korea. swsuh@hallym.ac.kr.
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Suh
mesh_terms: D000098:Acetophenones / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000831:Animals, Newborn; D001814:Blood-Testis Barrier / Q000503:physiopathology; D001921:Brain / Q000201:enzymology*; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000150:complications*; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D056784:Leukoencephalopathies / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology / Q000633:toxicity*; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000276:immunology / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000201:enzymology*
chemical_list: D000098:Acetophenones; D016207:Cytokines; D004791:Enzyme Inhibitors; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C445081:myelin oligodendrocyte glycoprotein (35-55); C056165:acetovanillone; D019255:NADPH Oxidases