Docosahexaenoic acid reduces cellular inflammatory response following permanent focal cerebral ischemia in rats

被引：95

作者：

Chang, Cheng-Yi ^{[1
]}

Kuan, Yu-Hsiang ^{[2
]}

Li, Jian-Ri ^{[3
]}

Chen, Wen-Ying ^{[4
]}

Ou, Yen-Chuan ^{[3
]}

Pan, Hung-Chuan ^{[5
]}

Liao, Su-Lan ^{[6
]}

Raung, Shue-Ling ^{[6
]}

Chang, Chen-Jung ^{[7
]}

Chen, Chun-Jung ^{[6
,8
,9
,10
,11
]}

机构：

[1] Fong Yuan Hosp, Dept Surg, Taichung 420, Taiwan

[2] Chung Shan Med Univ, Dept Pharmacol, Taichung 402, Taiwan

[3] Taichung Vet Gen Hosp, Div Urol, Taichung 407, Taiwan

[4] Natl Chung Hsing Univ, Dept Vet Med, Taichung 402, Taiwan

[5] Taichung Vet Gen Hosp, Dept Neurosurg, Taichung 407, Taiwan

[6] Taichung Vet Gen Hosp, Dept Educ & Res, Taichung 407, Taiwan

[7] Cent Taiwan Univ Sci & Technol, Dept Med Imaging & Radiol Sci, Taichung 406, Taiwan

[8] Natl Chung Hsing Univ, Inst Biomed Sci, Taichung 402, Taiwan

[9] Tunghai Univ, Ctr Gen Educ, Taichung 407, Taiwan

[10] HungKuang Univ, Grad Sch Nursing, Taichung 433, Taiwan

[11] China Med Univ, Dept Med Lab Sci & Biotechnol, Taichung 404, Taiwan

来源：

JOURNAL OF NUTRITIONAL BIOCHEMISTRY | 2013年 / 24卷 / 12期

关键词：

DHA; Neuroinflammation; Neuroprotection; Stroke; TRANSCRIPTION FACTOR NRF2; ARTERY-OCCLUSION; HEME OXYGENASE-1; BRAIN; INJURY; MODEL; INFILTRATION; ACTIVATION; EXPRESSION; MICROGLIA;

D O I：

10.1016/j.jnutbio.2013.08.004

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Cellular inflammatory response plays an important role in ischemic brain injury and anti-inflammatory treatments in stroke are beneficial. Dietary supplementation with docosahexaenoic acid (DHA) shows anti-inflammatory and neuroprotective effects against ischemic stroke. However, its effectiveness and its precise modes of neuroprotective action remain incompletely understood. This study provides evidence of an alternative target for DHA and sheds light on the mechanism of its physiological benefits. We report a global inhibitory effect of 3 consecutive days of DHA preadministration on circulating and intracerebral cellular inflammatory responses in a rat model of permanent cerebral ischemia. DHA exhibited a neuroprotective effect against ischemic deficits by reduction of behavioral disturbance, brain infarction, edema and blood-brain barrier disruption. The results of enzymatic assay, Western blot, real-time reverse transcriptase polymerase chain reaction and flow cytometric analysis revealed that DHA reduced central macrophages/microglia activation, leukocyte infiltration and pro-inflammatory cytokine expression and peripheral leukocyte activation after cerebral ischemia. In parallel with these immunosuppressive phenomena, DHA attenuated post-stroke oxidative stress, c-Jun N-terminal kinase (JNK) phosphorylation, c-Jun phosphorylation and activating protein-1 (AP-1) activation but further elevated ischemia-induced NF-E2-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1) expression. DHA treatment also had an immunosuppressive effect in lipopolysaccharide/interferon-gamma-stimulated glial cultures by attenuating JNK phosphorylation, c-Jun phosphorylation and AP-1 activation and augmenting Nrf2 and HO-1 expression. In summary, we have shown that DHA exhibited neuroprotective and anti-inflammatory effects against ischemic brain injury and these effects were accompanied by decreased oxidative stress and JNK/AP-1 signaling as well as enhanced Nrf2/HO-1 expression. (C) 2013 Elsevier Inc. All rights reserved.

引用

页码：2127 / 2137

页数：11

共 54 条

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