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N-3 polyunsaturated fatty acids induce granulopoiesis and early monocyte polarization in the bone marrow of a tMCAO rat model

Abstract Introduction: Experimental acute cerebral ischemia quickly triggers circulating inflammatory cells, provoking infiltration of neutrophils and macrophages in the damaged brain region. N-3 polyunsaturated fatty acids alleviate the ischemic deterioration, however, their potential effect on bone marrow cell mobilization is less known. Materials and methods: healthy male Wistar rats were submitted to intraperitoneal saline injection (n=10, sham Group), transient middle cerebral artery occlusion (tMCAO) and saline injection (n=10, placebo Group), tMCAO and highly purified fish-oil administration (n=10, T Group). At the two latter groups, twenty-four hours after tMCAO, MRI scans were performed to identify the ischemic regions; the eligible animals were sacrificed, the left parietal bones being removed and subjected to qualitative and quantitative histological and immunohistochemical analysis. Results: The active hematopoietic surface was maximal at the T-Group, being significantly lower in the P- and S-Groups (p=0.006 and p= 0.017). The MPO positive surface increased significantly in the T-compared to the S-Group (22.57± 0.86 % vs. 18.87± 0.68%, p= 0.004). Arg1 expression was significantly higher (p=0.001), while iNOS expression was lower (p=0.004) in the T- than in the P-Group, but similar to the S-group. The Arg1/iNOS2 ratio was higher in the FO-treated than in the P-group (p<0.001). Conclusion: the ischemic conditions triggered granulopoiesis and the increase of iNOS2 positive, type M1 macrophage in the rat bone marrow. Fish-oil treatment generated the expansion of overall hematopoietic surface along with normalization of iNOS2, up-regulating the potentially protective Arg1 positive M2 type macrophages and causing a significant shift in the M2/M1 ratio.