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- W3173801254 abstract "Objective To determine if leukemia inhibitory factor (LIF) administration after permanent focal stroke decreases post-stroke neuroinflammation. Methods Focal ischemia was induced in 3 month old male and 18 month old male/female Sprague-Dawley using the middle cerebral artery occlusion (MCAO) procedure. Animals were treated with PBS or LIF at 6, 24, and 48 h after MCAO (125 μg/kg). Animals were euthanized at at 72 h post-MCAO. Protein levels of CD11b, IL-12 p40, IFNγ, and IP-10 were measured in splenic tissue using immunoblotting and/or ELISA. Isolectin staining and immunoblotting were used to detect levels of CD11b+ macrophages/microglia in the brain. Murine bone marrow derived macrophages (BMDMs) stimulated with LPS (50 ng/ml) and IFNγ (20 ng/ml) in the presence or absense of LIF and IL-12 p40/IL-10 levels were detected in the supernatant. Results LIF treatment significantly increased the average spleen weight at 72 h after MCAO compared to PBS-treated rats (p<0.05) and decreased splenic LIFR expression compared to sham operated (p<0.01) and PBS-treated (p = 0.0682) rats. LIF-treated rats showed significantly decreased levels of IL-12 p40 (p <0.05) and IFNγ (p = 0.0644) in splenic tissue at 72 h after MCAO compared PBS-treated animals. LIF treatment also counteracted the significant increase in splenic IP-10 expression observed in the PBS-treated rats (*p<0.01 compared to sham-operated rats). CD11b levels were significantly lower in the spleens of LIF-treated (p<0.001) and PBS-treated (p<0.01) rats compared to sham rats. However, LIF treated significantly decreased normalized CD11b protein levels (p<0.05) and decreased isolectin reactivity in the brain at 72 h post-MCAO compared to PBS-treated animals. BMDMs treated with LIF prior to IFNγ and LPS stimulation released significantly lower levels of IL-12 p40 and significantly higher levels of IL-10 (p ≤ 0.05) compared to BMDMs treated with PBS prior to LPS+IFNγ stimulation. Conclusion LIF confers anti-inflammatory signaling after stroke through modulation of the IL-12 p40/IFNγ/IP-10 axis in splenocytes and decreasing the infiltration of CD11b+ monocytes/macrophages into the ischemic brain. Support or Funding Information Project Number: 5R01NS091146-03 (NINDS; PI: Pennypacker)Project Number: 55R01NS091582-03 (NINDS; PI: Gensel) This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal." @default.
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- W3173801254 date "2018-04-01" @default.
- W3173801254 modified "2023-10-16" @default.
- W3173801254 title "Leukemia Inhibitory Factor Modulates the Post‐Stroke Immune Response in Rats" @default.
- W3173801254 doi "https://doi.org/10.1096/fasebj.2018.32.1_supplement.824.4" @default.
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