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

Open access

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.

1. Takahashi Y, Yu Z, Sakai M, Tomita H. Linking Activation of Microglia and Peripheral Monocytic Cells to the Pathophysiology of Psychiatric Disorders. Front Cell Neurosci.2016 Jun;10:144. DOI: 10.3389/fncel.2016.00144

2. Wimmer I, Zrzavy T, Lassmann H. Neuroinflammatory responses in experimental and human stroke lesions. J Neuroimmunol.2018 Oct; 323:10-18. DOI: 10.1016/j.jneuroim.2018.07.003

3. Trépanier MO, Hopperton KE, Orr SK, Bazinet RP. N-3 polyunsaturated fatty acids in animal models with neuroinflammation: An update. Eur J Pharmacol. 2016 Aug;785:187-206. DOI: 10.1016/j.ejphar.2015.05.045

4. The World Health Organization (WHO) updates fact sheet on Top 10 causes of Death, https://community-medicine4asses.wordpress.com/2017/02/01/who-updates-fact-sheet-on-top-10-causes-of-death-27-january-2017/

5. Hermann DM, Kleinschnitz C, Gunzer M. Implications of polymorphonuclear neutrophils for ischemic stroke and intracerebral hemorrhage: Predictive value, patho-physiological consequences and utility as therapeutic target. J Neuroimmunol. 2018 Aug;321:138-43. DOI: 10.1016/j.jneuroim.2018.04.015

6. Jin R, Yang GJ, Li GH. Inflammatory mechanisms in ischemic stroke: role of inflammatory cells. J Leukoc Biol. 2010 May;87(5):779-89. DOI: 10.1189/jlb.1109766

7. Ceulemans A-G, Zgavc T, Kooijman R, Hachimi-Idrissi S, Sarre S, Michotte Y. The dual role of the neuroinflammatory response after ischemic stroke: modulatory effects of hypothermia. J Neuroinflammation 2010 Nov;7:74. DOI: 10.1186/1742-2094-7-74. DOI: 10.1186/1742-2094-7-74

8. Kriz J. Inflammation in ischemic brain injury: timing is important. Crit Rev Neurobiol. 2006;18 (1-2): 145-57. DOI: 10.1615/CritRevNeurobiol.v18.i1-2.150. DOI: 10.1615/CritRevNeurobiol.v18.i1-2.150

9. Grönberg NV, Johansen FF, Kristiansen U, Hasseldam H. Leukocyte infiltration in experimental stroke. J Neuroinflammation 2013 Sep; 10: 115. DOI: 10.1186/1742-2094-10-115

10. Ritzel RM, Patel AR, Grenier JM, Crapser J, Verma R, Jellison ER, et al. Functional differences between microglia and monocytes after ischemic stroke. J Neuroinflammation. 2015 May; 12:106. DOI: 10.1186/s12974-015-0329-1

11. Boche D, Perry VH, Nicoll JA. Activation patterns of microglia and their identification in the human brain. Neuropathol Appl Neurobiol. 2013 Feb;39(1):3-18. DOI: 10.1111/nan.12011

12. Ma Y, Wang J, Wang Y, Yang GY. The biphasic function of microglia in ischemic stroke. Prog Neurobiol. 2017 Oct; 157:247-72. DOI: 10.1016/j.pneurobio.2016.01.005

13. Xiong XY, Liu L, Yang QW. Functions and mechanisms of microglia/macrophages in neuroinflammation and neurogenesis after stroke. Prog Neurobiol. 2016 Jul;142:23-44. DOI: 10.1016/j.pneurobio.2016.05.001

14. Kanazawa M, Ninomiya I, Hatakeyama M, Takahashi T, Shimohata T. Microglia and monocytes/macrophages polarization reveal novel therapeutic mechanism against stroke. Int J Mol Sci. 2017 Oct;13:18(10). pii: E2135.

15. Gliem M, Schwaninger M, Jander S. Protective features of peripheral monocytes/macrophages in stroke. Biochim Biophys Acta. 2016 Mar;1862(3):329-38. DOI: 10.1016/j.bbadis.2015.11.004

16. Courties G, Herisson F, Sager HB, Heidt T, Ye Y, Wei Y, et al. Ischemic stroke activates hematopoietic bone marrow cells. Circ Res. 2015 Jan;116(3):407-17. DOI: 10.1161/CIRCRESAHA.116.305207

17. Wolf D, Ley K. Waking up the stem cell niche: how hematopoietic stem cells generate inflammatory monocytes after stroke. Circ Res. 2015 Jan;116(3):389-92. DOI: 10.1161/CIRCRESAHA.114.305678

18. Orădan A, Huțanu A, Horváth E, Chiriac L, Dobreanu M. Improved rat stroke model by intraluminal middle cerebral artery occlusion: a special emphasis on surgical technique. Health Problems of Civilization 2017;11:202-10. DOI: 10.5114/hpc.2017.70008

19. Mezei T, Horváth E, Turcu M, Gurzu S, Raica M, Jung I. Microvascular density in non-Hodgkin B-cell lymphomas measured using digital morphometry. Rom J Morphol Embryol. 2012; 53(1):67–71.

20. Horváth E, Adina Hutanu A, Chiriac L, Dobreanu M, Orădan A, Nagy EE. Ischemic damage and early inflammatory infiltration are different in the core and penumbra lesions of rat brain after transient focal cerebral ischemia. J Neuroimmunol. 2018;324:35-42. DOI: 10.1016/j.jneuroim.2018.08.002

21. Romaniuc A, Lyndina Y, Sikora V, Lyndin M, Karpenko L, Gladchenko O, et al. Structural features of bone marrow. Interv Med Appl Sci 2016 Sep;8(3):121-6. DOI: 10.1556/1646.8.2016.3.3

22. Kozlowski C, Fullerton A, Cain G, Katavolos P, Bravo J, Tarrant JM. Proof of concept for an automated image analysis method to quantify rat bone marrow hematopoietic lineages on H&E sections. Toxicol Pathol 2018 Apr;46(3):336-47. DOI: 10.1177/0192623318766458

23. Limbkar K, Dhenge A, Jadhav DD, Thulasiram HV, Kale V, Limaye L et al. Oral feeding with polyunsaturated fatty acids fosters hematopoiesis and thrombopoiesis in healthy and bone marrow-transplanted mice. J Nutr Biochem. 2017 Sep;47:94-105. DOI: 10.1016/j.jnutbio.2017.05.002

24. Xia S, Li XP, Cheng L, Han MT, Zhang MM, Shao QX, et al. Fish Oil-Rich Diet Promotes Hematopoiesis and Alters Hematopoietic Niche. Endocrinology 2015 Aug;156(8):2821-30. DOI: 10.1210/en.2015-1258

25. Svan SL, Varemo L, Gabrielsson BG, Peris E, Nookaew I, Grahnemo L, et al. Six tissue transcriptomics reveals specific immune suppression in spleen by dietary polyunsaturated fatty acids. PLoS One 2016 May; 11 (5): e0155099. DOI: 10.1371/journal.pone.0155099

26. ElAli A, Jean LeBlanc N. The role of monocytes in ischemic stroke pathobiology: New avenues to explore. Front Aging Neurosci. 2016 Feb;8:29. DOI: 10.3389/fnagi.2016.00029

27. Nakagawa Y, Chiba K. Role of microglial M1/M2 polarisation in relapse and remission of psychiatric disorders and diseases. Pharmaceuticals (Basel) 2014 Nov; 7(12): 1028-48. DOI: 10.3390/ph7121028

28. Rath M, Müller I, Kropf P, Closs EI, Munder M. Metabolism via Arginase or Nitric Oxide Synthase: Two Competing Arginine Pathways in Macrophages. Front Immunol. 2014 Oct;5:532. DOI: 10.3389/fimmu.2014.00532

Revista Romana de Medicina de Laborator

Romanian Journal of Laboratory Medicine

Journal Information


IMPACT FACTOR 2018: 0,800
5-year IMPACT FACTOR: 0,655



CiteScore 2017: 0.31

SCImago Journal Rank (SJR) 2018: 0.194
Source Normalized Impact per Paper (SNIP) 2018: 0.306

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 112 112 18
PDF Downloads 64 64 5