title: K(+) channel blocker-induced neuroinflammatory response and neurological disorders: immunomodulatory effects of astaxanthin.
abstract: OBJECTIVE
  Channelopathies due to the brain ion channel dysfunction is considered to be an important mechanism involved in various neurodegenerative diseases. In this study, we evaluated the ability of kaliotoxin (KTX) as K(+) channel blocker to induce neuro-inflammatory response and neurodegenerative alteration. We also investigate the effects of astaxanthin (ATX) against KTX disorders.
  
  
  METHODS
  NMRI mice were injected with KTX (1 pg/kg, by i.c.v route) with or without pretreatment using ATX (80 mg/kg, o.p route).
  
  
  RESULTS
  Results showed that KTX was detected in cerebral cortex area due to its binding to the specific receptors (immunofluorescence analysis). It induced an activation of inflammatory cascade characterized by an increase of IL-6, TNFα, NO, MDA levels and NF-κB expression associated to a decrease of GSH level. The neuroinflammatory response is accompanied with cerebral alterations and blood-brain barrier (BBB) disruption. The use of ATX prior to the KTX exerts a preventive effect not only on the neuroinflammation but also on altered tissues and the BBB disruption.
  
  
  CONCLUSIONS
  Kaliotoxin is able to induce neurological disorders by blocking the K(+) ion channel, and ATX suppresses this alterations with down regulation of IL-6, TNF-α and NF-κB expression in the brain.
authors.affiliation: USTHB, Faculty of Biological Sciences, Laboratory of Cellular and Molecular Biology, BP32, El Alia, Bab Ezzouar, 16111, Algiers, Algeria.
authors.forename: Nesrine
authors.initials: N
authors.lastname: Sifi
authors.affiliation: CRN2M UMR 7286, CNRS, Aix Marseille Université, 13344, Marseille Cedex 15, France.
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Martin-Eauclaire
authors.affiliation: USTHB, Faculty of Biological Sciences, Laboratory of Cellular and Molecular Biology, BP32, El Alia, Bab Ezzouar, 16111, Algiers, Algeria. flaraba@hotmail.com.
authors.forename: Fatima
authors.initials: F
authors.lastname: Laraba-Djebari
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002374:Catalase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007155:Immunologic Factors / Q000494:pharmacology*; D015850:Interleukin-6 / Q000276:immunology; D008315:Malondialdehyde / Q000276:immunology; D051379:Mice; D016328:NF-kappa B / Q000276:immunology; D009422:Nervous System Diseases / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000276:immunology; D026902:Potassium Channel Blockers; D012604:Scorpion Venoms; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D024341:Xanthophylls / Q000494:pharmacology
chemical_list: D007155:Immunologic Factors; D015850:Interleukin-6; D016328:NF-kappa B; D026902:Potassium Channel Blockers; D012604:Scorpion Venoms; D014409:Tumor Necrosis Factor-alpha; D024341:Xanthophylls; C577686:interleukin-6, mouse; C072276:kaliotoxin; D009569:Nitric Oxide; D008315:Malondialdehyde; C005948:astaxanthine; D002374:Catalase; D005978:Glutathione
keywords: Astaxanthin; Blood–brain barrier; K+ channel blocker; Neurodegeneration; Neuroinflammatory response; Neurotoxin