Post-stroke DHA Treatment Protects Against Acute Ischemic Brain Injury by Skewing Macrophage Polarity Toward the M2 Phenotype

被引:66
作者
Cai, Wei [1 ,2 ]
Liu, Sanxin [1 ]
Hu, Mengyan [1 ]
Sun, Xiaobo [1 ]
Qiu, Wei [1 ]
Zheng, Songguo [2 ]
Hu, Xiaoming [3 ]
Lu, Zhengqi [1 ]
机构
[1] Sun Yat Sen Univ, Dept Neurol, Affiliated Hosp 3, 600 Tianhe Rd, Guangzhou 510630, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Ctr Clin Immunol, Affiliated Hosp 3, Guangzhou, Guangdong, Peoples R China
[3] Univ Pittsburgh, Sch Med, Ctr Cerebrovasc Dis Res, Pittsburgh, PA 15213 USA
基金
中国国家自然科学基金;
关键词
Cerebral ischemia; Macrophage; Chemokine; Cytokine; DHA; Neuroprotection; FOCAL CEREBRAL-ISCHEMIA; POLYUNSATURATED FATTY-ACIDS; CENTRAL-NERVOUS-SYSTEM; DOCOSAHEXAENOIC ACID; INTRACEREBRAL HEMORRHAGE; MICROGLIA/MACROPHAGE POLARIZATION; MICROGLIAL RESPONSES; EXPERIMENTAL STROKE; CELLS; NEUROPROTECTION;
D O I
10.1007/s12975-018-0662-7
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Systemic docosahexaenoic acid (DHA) has been explored as a clinically feasible protectant in stroke models. However, the mechanism for DHA-afforded neuroprotection remains elusive. Transient middle cerebral artery occlusion (tMCAO) was induced for 1h. DHA (i.p., 10mg/kg) was administered immediately after reperfusion and repeated daily for 3days. Stroke outcomes, systemic inflammatory status, and microglia/macrophage phenotypic alterations were assessed 3days after stroke. Macrophage depletion was induced by clodronate liposomes injection. Primary macrophage cultures were used to evaluate the direct effect of DHA on macrophages. We demonstrated that post-stroke DHA injection efficiently reduced brain infarct and ameliorated neurological deficits 3days after tMCAO. Systemic DHA treatment significantly inhibited immune cell infiltration (macrophages, neutrophils, T lymphocytes, and B lymphocytes) and promoted macrophage polarization toward an anti-inflammatory M2 phenotype in the ischemic brain. Meanwhile, systemic DHA administration inhibited the otherwise elevated pro-inflammatory factors in blood and shifted circulating macrophage polarity toward M2 phenotype after ischemic stroke. The numbers of circulating immune cells in blood and spleen, however, were equivalent between DHA- and vehicle-treated groups. The protective effects of DHA were macrophage-dependent, as macrophage depletion abolished DHA-afforded neuroprotection. In vitro studies confirmed that DHA suppressed production of chemokines and pro-inflammatory cytokines from macrophages under inflammatory stimulation. These data indicate that post-stroke DHA treatment ameliorated acute ischemic brain injury in a macrophage-dependent manner and DHA enhanced macrophage phenotypic shift toward an anti-inflammatory phenotype to reduced central and peripheral inflammation after stroke.
引用
收藏
页码:669 / 680
页数:12
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