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標題: Protective effect of docosahexaenoic acid against brain injury in ischemic rats
作者: Pan, H.C.
Kao, T.K.
Ou, Y.C.
Yang, D.Y.
Yen, Y.J.
Wang, C.C.
Chuang, Y.H.
Liao, S.L.
Raung, S.L.
Wu, C.W.
Chiang, A.N.
Chen, C.J.
關鍵字: Apoptosis;Cerebral ischemia/reperfusion;DHA;Inflammation;Neuroprotection;Oxidative stress;focal cerebral-ischemia;polyunsaturated fatty-acids;cell-death;neuronal apoptosis;blood-flow;bcl-2;infarction;expression;stroke;ischemia/reperfusion
Project: Journal of Nutritional Biochemistry
期刊/報告no:: Journal of Nutritional Biochemistry, Volume 20, Issue 9, Page(s) 715-725.
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 I It 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 kappa beta inactivation. Therefore, the data Suggest that the neuroprotectivc 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. (C) 2009 Elsevier Inc. All rights reserved.
ISSN: 0955-2863
DOI: 10.1016/j.jnutbio.2008.06.014
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