resolvin-d2 and Ischemic-Stroke

Inflammation plays an important role in diabetes mellitus (DM)-related acute ischemic stroke (AIS). The mechanisms of un-resolved inflammation in DM-related AIS are not fully understood. Specialized pro-resolving mediators (SPMs) are key regulators that promote resolution of inflammation. We aimed to examine resolution function in patients with AIS complicated with DM, and explore potential treatment effects of one of the SPMs, resolvin D2 (RvD2) ex vivo and in vivo.. Cultured human macrophages, which were derived from peripheral blood mononuclear cells of AIS and none-AIS patients with or without DM, were stimulated with oxidized-low density lipoprotein (ox-LDL). Levels of SPMs and inflammatory markers were analysed, and RvD2 treatment effects were evaluated in these cells. For experiments in vivo, challenges with high fat diet and low-dose streptozotocin (STZ) were used to induce DM in C57BL/6J mice. AIS model was established by permanent middle cerebral artery occlusion (pMCAO) followed by intra-cerebroventricular injection of RvD2.. Our data demonstrate resolution of inflammation is impaired by DM in AIS patients, implicating a novel mechanism of un-resolved inflammation in DM-related AIS. Furthermore, RvD2 promotes inflammation resolution in macrophages/microglia and protects DM-related AIS, and may thus serve as a novel therapeutic target.

Topics: Animals; Diabetes Mellitus; Docosahexaenoic Acids; Humans; Infarction, Middle Cerebral Artery; Inflammation; Ischemic Stroke; Leukocytes, Mononuclear; Mice; Mice, Inbred C57BL