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

Abstract：

: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 1 h. DHA (i.p., 10 mg/kg) was administered immediately after reperfusion and repeated daily for 3 days. Stroke outcomes, systemic inflammatory status, and microglia/macrophage phenotypic alterations were assessed 3 days 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 3 days 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.

journal_name

Transl Stroke Res

journal_title

Translational stroke research

authors

Cai W,Liu S,Hu M,Sun X,Qiu W,Zheng S,Hu X,Lu Z

doi

10.1007/s12975-018-0662-7

subject

Has Abstract

pub_date

2018-12-01 00:00:00

pages

669-680

issue

eissn

1868-4483

issn

1868-601X

pii

10.1007/s12975-018-0662-7

journal_volume

pub_type

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