Endovascular Stem Cell Therapy
The impact of increased BDNF expression in the brain by endovascular delivered mesenchymal stem cells (MSCs) post stroke towards modulating endoplasmic reticulum (ER) stress-mediated neuronal remodeling has not been directly studied. Therefore, the present study investigates ER stress-mediated neuronal remodeling following IA MSCs infusion in a rodent model of ischemic stroke.
Methods: Ovariectomized Sprague Dawley rats were subjected to MCAO followed by 1 × 105 IA MSCs administration at 6 h. Infarct and functional outcomes at different time points post-stroke were evaluated. Further, various gene and protein expression studies were performed to determine the underlying mechanisms of the effect of IA MSCs towards ER stress-mediated neuronal remodeling.
Results: Post-stroke IA MSCs administration significantly increased BDNF expression and decreased ER stress markers expression at day 1 post-stroke. A gradual rise in the expression of growth associate protein-43 (GAP 43) and spinophilin were observed at 7, 14- and 28-days post-stroke indicating an increase in neuronal remodeling towards functional restoration.
The results suggest that IA MSCs post-stroke can modulate neuronal remodeling by BDNF-mediated reduction in ER stress that contributes towards functional recovery 1).