Research Paper Volume 13, Issue 2 pp 3060—3079

Human umbilical cord mesenchymal stem cell-derived exosomal miR-146a-5p reduces microglial-mediated neuroinflammation via suppression of the IRAK1/TRAF6 signaling pathway after ischemic stroke

Treatment with hUMSC-Exos decreases neuroinflammation and is neuroprotective by down-regulating IRAK1/TRAF6 signaling pathway activity in vivo. (A) Representative photomicrographs of TTC-stained tissue from wild-type versus miR-146a-5p knockdown hUMSC-Exos groups, with infarct size as calculated using ImageJ software. Data are expressed as mean ± SEM (n = 6 per group). Significant differences are indicated (*p B, C) Neurological deficit scores in vehicle-only versus experimental groups at 72 hours post-reperfusion. Data are expressed as mean ± SEM (n = 12 per group). Significant differences are indicated (*p **p D, E) Representative photomicrographs of IL-6 and NFκB in the ischemic penumbra 72 hours post-reperfusion, with associated relative intensities as calculated using ImageJ software. Scale bar: 50 μm. Data are expressed as mean ± SEM (n = 6 per group). Significant differences are indicated (*p F) Microglial M1 markers IBA-1 and CD16 in the ischemic penumbra 3 days following ischemic stroke. (G) Expression of signaling pathway IRAK1, TRAF6, and NFκB (p65) in the wild-type versus miR-146a-5p knockdown groups. (H) Determination of IL-6, TNF- α, and IL-1β protein levels via ELISA. Data are expressed as mean ± SEM (experiments were performed in triplicate). Significant differences are indicated (*p

Figure 6. Treatment with hUMSC-Exos decreases neuroinflammation and is neuroprotective by down-regulating IRAK1/TRAF6 signaling pathway activity in vivo. (A) Representative photomicrographs of TTC-stained tissue from wild-type versus miR-146a-5p knockdown hUMSC-Exos groups, with infarct size as calculated using ImageJ software. Data are expressed as mean ± SEM (n = 6 per group). Significant differences are indicated (*p < 0.05). (B, C) Neurological deficit scores in vehicle-only versus experimental groups at 72 hours post-reperfusion. Data are expressed as mean ± SEM (n = 12 per group). Significant differences are indicated (*p < 0.05, **p < 0.01). (D, E) Representative photomicrographs of IL-6 and NFκB in the ischemic penumbra 72 hours post-reperfusion, with associated relative intensities as calculated using ImageJ software. Scale bar: 50 μm. Data are expressed as mean ± SEM (n = 6 per group). Significant differences are indicated (*p < 0.05). (F) Microglial M1 markers IBA-1 and CD16 in the ischemic penumbra 3 days following ischemic stroke. (G) Expression of signaling pathway IRAK1, TRAF6, and NFκB (p65) in the wild-type versus miR-146a-5p knockdown groups. (H) Determination of IL-6, TNF- α, and IL-1β protein levels via ELISA. Data are expressed as mean ± SEM (experiments were performed in triplicate). Significant differences are indicated (*p < 0.05, **p < 0.01, ***p < 0,001).