Abstract 4020: The Novel TrkB Agonist, 7,8-Dihydroxyflavone Enhances Stem Cell Mobilization After Stroke.
Background: Increasing levels of circulating Hematopoietic Stem Cells (HSC)/Hematopoietic Progenitor Cells (HPC), bone marrow derived mononuclear cells that promote repair in areas of injury, have been demonstrated to correlate with improved neurological function following stroke, suggesting a potentially critical role for HSC/HPC’s in limiting stroke injury and/or facilitating stroke recovery. Flavonoids, found in plants and fruit, exert anti-oxidative effects. Recent studies have demonstrated that 7,8 Dihydroxyflavone (DHF) is a potent TrkB agonist mimicking Brain Derived Neurotropic Factor, thus making it a powerful potential tool for treating neurological disorders. Stromal Derived Growth Factor 1-Alpha (SDF1-A) along with its receptor CXCR4 is a potent chemo attractant released by areas of injury. SDF1-A has been shown to mobilize HSC/HPC from the bone marrow to the blood and lead to ‘homing’ of the cells to an area of injury. We investigated the effect of DHF on HSC/HPC function following cerebral ischemia.
Methods: Ischemic damage was induced in adult male Long Evans hooded rats (350-400g) with a peri-MCA injection of the vasoconstriction peptide ET-1. The rats were sacrificed at 24 hours post surgery and their bone marrow and blood HSC/HPC enriched using nanoparticles tagged with LIN negative and CD90 markers.
Results: Stroked animals showed an increase in bone marrow production of HSC/HPC versus control animals (31.9±7 versus 2±0.5, p<0.05). The mobilization of the HSC/HPC from the bone marrow to the blood was also significantly higher in the stroked animals versus control animals (43±19 versus 3.6±0.3, p<0.05). Following stroke, DHF pre-treated HSC/HPC’s demonstrated significantly improved migration along an SDF-1 gradient compared to controls (129±1.0 versus 108±1.15, p<0.05), despite the fact that DHF alone provided no independent migratory stimulus.
Conclusions: The results suggest that DHF may be a viable compound to facilitate HSC/HPC migration post-stroke.
- © 2012 by American Heart Association, Inc.