Harpreet Kaur1, Deepaneeta Sarmah1, Aishika Datta1, Anupom Borah2, Dileep R Yavagal3, Pallab Bhattacharya4. 1. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), Gandhinagar, Gujarat, 382355, India. 2. Cellular and Molecular Neurobiology Laboratory, Department of Life Science and Bioinformatics, Assam University, Silchar, Assam, 788011, India. 3. Department of Neurology and Neurosurgery, University of Miami Miller School of Medicine, Miami, FL, 33136, USA. 4. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), Gandhinagar, Gujarat, 382355, India. pallab.bhu@gmail.com.
Abstract
BACKGROUND AND PURPOSE: The impact of increased BDNF expression in 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 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 genes 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. CONCLUSIONS: The results suggest that IA MSCs post-stroke can modulate neuronal remodeling by BDNF-mediated reduction in ER stress that contribute towards functional recovery.
BACKGROUND AND PURPOSE: The impact of increased BDNF expression in 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 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 genes 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. CONCLUSIONS: The results suggest that IA MSCs post-stroke can modulate neuronal remodeling by BDNF-mediated reduction in ER stress that contribute towards functional recovery.
Authors: Dileep R Yavagal; Baowan Lin; Ami P Raval; Philip S Garza; Chuanhui Dong; Weizhao Zhao; Erika B Rangel; Ian McNiece; Tatjana Rundek; Ralph L Sacco; Miguel Perez-Pinzon; Joshua M Hare Journal: PLoS One Date: 2014-05-07 Impact factor: 3.240