title: Docosahexaenoic acid attenuates the early inflammatory response following spinal cord injury in mice: in-vivo and in-vitro studies.
abstract: BACKGROUND
  Two families of polyunsaturated fatty acid (PUFA), omega-3 (ω-3) and omega-6 (ω-6), are required for physiological functions. The long chain ω-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have significant biological effects. In particular, DHA is a major component of cell membranes in the brain. It is also involved in neurotransmission. Spinal cord injury (SCI) is a highly devastating pathology that can lead to catastrophic dysfunction, with a significant reduction in the quality of life. Previous studies have shown that EPA and DHA can exert neuroprotective effects in SCI in mice and rats. The aim of this study was to analyze the mechanism of action of ω-3 PUFAs, such as DHA, in a mouse model of SCI, with a focus on the early pathophysiological processes.
  
  
  METHODS
  In this study, SCI was induced in mice by the application of an aneurysm clip onto the dura mater via a four-level T5 to T8 laminectomy. Thirty minutes after compression, animals received a tail vein injection of DHA at a dose of 250 nmol/kg. All animals were killed at 24 h after SCI, to evaluate various parameters implicated in the spread of the injury.
  
  
  RESULTS
  Our results in this in-vivo study clearly demonstrate that DHA treatment reduces key factors associated with spinal cord trauma. Treatment with DHA significantly reduced: (1) the degree of spinal cord inflammation and tissue injury, (2) pro-inflammatory cytokine expression (TNF-α), (3) nitrotyrosine formation, (4) glial fibrillary acidic protein (GFAP) expression, and (5) apoptosis (Fas-L, Bax, and Bcl-2 expression). Moreover, DHA significantly improved the recovery of limb function.Furthermore, in this study we evaluated the effect of oxidative stress on dorsal root ganglion (DRG) cells using a well-characterized in-vitro model. Treatment with DHA ameliorated the effects of oxidative stress on neurite length and branching.
  
  
  CONCLUSIONS
  Our results, in vivo and in vitro, clearly demonstrate that DHA treatment reduces the development of inflammation and tissue injury associated with spinal cord trauma.
authors.forename: Irene
authors.initials: I
authors.lastname: Paterniti
authors.forename: Daniela
authors.initials: D
authors.lastname: Impellizzeri
authors.forename: Rosanna
authors.initials: R
authors.lastname: Di Paola
authors.forename: Emanuela
authors.initials: E
authors.lastname: Esposito
authors.forename: Stacy
authors.initials: S
authors.lastname: Gladman
authors.forename: Ping
authors.initials: P
authors.lastname: Yip
authors.forename: John V
authors.initials: JV
authors.lastname: Priestley
authors.forename: Adina T
authors.initials: AT
authors.lastname: Michael-Titus
authors.affiliation: Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 98166 Messina, Italy. salvator@unime.it.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000627:therapeutic use*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology; D066298:In Vitro Techniques; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology*; D007796:Laminectomy; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009069:Movement Disorders / Q000188:drug therapy / Q000209:etiology; D016501:Neurites / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D047493:PPAR alpha / Q000172:deficiency; D013119:Spinal Cord Injuries / Q000150:complications*; D019014:fas Receptor / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; C491899:Fas protein, mouse; D015525:Fatty Acids, Omega-3; D047493:PPAR alpha; D019014:fas Receptor; D004281:Docosahexaenoic Acids