Seyyed Mohyeddin Ziaee1,2,3, Parisa Tabeshmehr3, Khawaja Husnain Haider4, Majidreza Farrokhi5,6, Abdolhamid Shariat5,7, Atena Amiri5, Seyed Mojtaba Hosseini1,2,3. 1. Student Research Committee, Medical Faculty, Shiraz University of Medical Sciences, Shiraz, Iran. 2. Stem Cell Laboratory, Department of Anatomy, Medical Faculty, Shiraz University of Medical Sciences, Shiraz, Iran. 3. Cell & Molecular Medicine Student Research Group, Medical Faculty, Shiraz University of Medical Sciences, Shiraz, Iran. 4. Department of Basic Sciences, SRU, Saudi Arabia. 5. Shiraz Neuroscience Research Center, Department of Neurology, Shiraz University of Medical Sciences, Shiraz, Iran. 6. Neurosurgery Department, Department of Neurology, Shiraz University of Medical Sciences, Shiraz, Iran. 7. Clinical Neurology Research Center, Department of Neurology, Shiraz University of Medical Sciences, Shiraz, Iran.
Abstract
BACKGROUND: Despite encouraging data in terms of neurological outcome, stem cell based therapy for ischemic stroke in experimental models and human patients is still hampered by multiple as yet un-optimized variables, i.e., time of intervention, that significantly influence the prognosis. The aim of the present study was to delineate the optimum time for neural stem cells (NSCs) transplantation after ischemic stroke. METHODS: The NSCs were isolated from 14 days embryo rat ganglion eminence and were cultured in NSA medium (neurobasal medium, 2% B27, 1% N2, bFGF 10 ng/mL, EGF 20 ng/mL and 1% pen/strep). The cells were characterized for tri-lineage differentiation by immunocytochemistry for tubulin-III, Olig2 and GFAP expression for neurons, oligodendrocytes and astrocyte respectively. The NSCs at passage 3 were injected intraventricularly in a rodent model of middle-cerebral artery occlusion (MCAO) on stipulated time points of 1 & 12 h, and 1, 3, 5 and 7 days after ischemic stroke. The animals were euthanized on day 28 after their respective treatment. RESULTS: dUTP nick end labeling (TUNEL) assay and Caspase assay showed significantly reduced number of apoptotic cells on day 3 treated animals as compared to the other treatment groups of animals. The neurological outcome showed that the group which received NSCs 3 days after brain ischemia had the best neurological performance. CONCLUSIONS: The optimum time for NSCs transplantation was day 3 after ischemic stroke in terms of attenuation of ischemic zone expansion and better preserved neurological performance.
BACKGROUND: Despite encouraging data in terms of neurological outcome, stem cell based therapy for ischemic stroke in experimental models and humanpatients is still hampered by multiple as yet un-optimized variables, i.e., time of intervention, that significantly influence the prognosis. The aim of the present study was to delineate the optimum time for neural stem cells (NSCs) transplantation after ischemic stroke. METHODS: The NSCs were isolated from 14 days embryo rat ganglion eminence and were cultured in NSA medium (neurobasal medium, 2% B27, 1% N2, bFGF 10 ng/mL, EGF 20 ng/mL and 1% pen/strep). The cells were characterized for tri-lineage differentiation by immunocytochemistry for tubulin-III, Olig2 and GFAP expression for neurons, oligodendrocytes and astrocyte respectively. The NSCs at passage 3 were injected intraventricularly in a rodent model of middle-cerebral artery occlusion (MCAO) on stipulated time points of 1 & 12 h, and 1, 3, 5 and 7 days after ischemic stroke. The animals were euthanized on day 28 after their respective treatment. RESULTS:dUTP nick end labeling (TUNEL) assay and Caspase assay showed significantly reduced number of apoptotic cells on day 3 treated animals as compared to the other treatment groups of animals. The neurological outcome showed that the group which received NSCs 3 days after brain ischemia had the best neurological performance. CONCLUSIONS: The optimum time for NSCs transplantation was day 3 after ischemic stroke in terms of attenuation of ischemic zone expansion and better preserved neurological performance.
Authors: Claudia Bühnemann; Andreas Scholz; Christian Bernreuther; Christoph Y Malik; Holger Braun; Melitta Schachner; Klaus G Reymann; Marcel Dihné Journal: Brain Date: 2006-10-03 Impact factor: 13.501
Authors: Joanna M Wardlaw; Veronica Murray; Eivind Berge; Gregory del Zoppo; Peter Sandercock; Richard L Lindley; Geoff Cohen Journal: Lancet Date: 2012-05-23 Impact factor: 79.321
Authors: Austin C Boese; Quan-Son Eric Le; Dylan Pham; Milton H Hamblin; Jean-Pyo Lee Journal: Stem Cell Res Ther Date: 2018-06-13 Impact factor: 6.832