title: Protective effect of docosahexaenoic acid against brain injury in ischemic rats.
abstract: Evidence suggests that inactivation of cell-damaging mechanisms and/or activation of cell-survival mechanisms may provide effective preventive or therapeutic interventions to reduce cerebral ischemia/reperfusion (I/R) injuries. Docosahexaenoic acid (DHA) is an essential polyunsaturated fatty acid in the central nervous system that has been shown to possess neuroprotective effects. We examined whether different preadministrative protocols of DHA have effects on brain injury after focal cerebral I/R and investigated the potential neuroactive mechanisms involved. Sprague-Dawley rats were intraperitoneally pretreated with DHA once 1 h or 3 days being subjected to focal cerebral I/R or daily for 6 weeks before being subjected to focal cerebral I/R. Reduction of brain infarction was found in all three DHA-pretreated groups. The beneficial effect of DHA on the treatment groups was accompanied by decreases in blood-brain barrier disruption, brain edema, malondialdehyde (MDA) production, inflammatory cell infiltration, interleukin-6 (IL-6) expression and caspase-3 activity. Elevation of antioxidative capacity, as evidenced by decreased MDA level and increased superoxide dismutase activity and glutathione level, was detected only in the chronic daily-administration group. The two single-administration groups showed increased phosphorylation of extracellular-signal-regulated kinase (ERK). Elevation of Bcl-2 expression was detected in the chronic daily-administration and 3-day-administration groups. In vitro study demonstrated that DHA attenuated IL-6 production from stimulated glial cells involving nuclear factor kappaB inactivation. Therefore, the data suggest that the neuroprotective mechanisms of DHA pretreatment are, in part, mediated by attenuating damaging mechanisms through reduction of cytotoxic factor production and by strengthening survival mechanisms through ERK-mediated and/or Bcl-2-mediated prosurvival cascade.
authors.affiliation: Chung Hwa University of Medical Technology, Tainan, Taiwan.
authors.forename: Hung-Chuan
authors.initials: HC
authors.lastname: Pan
authors.forename: Tsung-Kuei
authors.initials: TK
authors.lastname: Kao
authors.forename: Yen-Chuan
authors.initials: YC
authors.lastname: Ou
authors.forename: Dar-Yu
authors.initials: DY
authors.lastname: Yang
authors.forename: Yu-Ju
authors.initials: YJ
authors.lastname: Yen
authors.forename: Chun-Chiang
authors.initials: CC
authors.lastname: Wang
authors.forename: Yu-Han
authors.initials: YH
authors.lastname: Chuang
authors.forename: Su-Lan
authors.initials: SL
authors.lastname: Liao
authors.forename: Shue-Ling
authors.initials: SL
authors.lastname: Raung
authors.forename: Ching-Wen
authors.initials: CW
authors.lastname: Wu
authors.forename: An-Na
authors.initials: AN
authors.lastname: Chiang
authors.forename: Chun-Jung
authors.initials: CJ
authors.lastname: Chen
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000503:physiopathology; D001929:Brain Edema / Q000517:prevention & control; D020520:Brain Infarction / Q000517:prevention & control*; D053148:Caspase 3 / Q000378:metabolism; D020214:Cerebrovascular Trauma / Q000517:prevention & control*; D004281:Docosahexaenoic Acids / Q000008:administration & dosage* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D020925:Hypoxia-Ischemia, Brain / Q000517:prevention & control*; D015850:Interleukin-6 / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D016328:NF-kappa B; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D004281:Docosahexaenoic Acids; D013482:Superoxide Dismutase; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3; D005978:Glutathione