Dorit Granot1, Erik M Shapiro. 1. Department of Diagnostic Radiology, Molecular and Cellular MRI Laboratory, Yale University School of Medicine, New Haven, Connecticut, USA.
Abstract
PURPOSE: Endogenous labeling of stem/ progenitor cells via intracerebroventricular injection of micron-sized particles of iron oxide (MPIOs) has become standard methodology for MRI of adult neurogenesis. While this method is well characterized in the naïve rodent brain, it has not been fully investigated in disease models. Here, we describe methodological challenges that can confound data analysis when this technique is applied to a rat model of stroke, the endothelin-1 model of focal cortical ischemia. METHODS: We intended to track endogenous neuroblast migration from the subventricular zone to the stroke area using previously described methods for in vivo labeling of endogenous neuroblasts with MPIOs and following migration with high resolution MRI. RESULTS: MPIOs accumulation in stroke regions of endothelin-1-treated brains involves two dynamic steps: an initial rapid cell independent mechanism, followed by slower MPIOs accumulation. While the latter may in part be attributable to cell dependent delivery of the particles, the cell independent mechanism complicates the interpretation of the data. Strategies aimed at prelabeling the stem cell niche reduced cell independent MPIOs accumulation, but failed to abolish it. CONCLUSION: We conclude that MRI-based neural stem/progenitor cell tracking via direct injection of MPIOs into the lateral and third ventricles, requires significant validation in models of brain disease/trauma.
PURPOSE: Endogenous labeling of stem/ progenitor cells via intracerebroventricular injection of micron-sized particles of iron oxide (MPIOs) has become standard methodology for MRI of adult neurogenesis. While this method is well characterized in the naïve rodent brain, it has not been fully investigated in disease models. Here, we describe methodological challenges that can confound data analysis when this technique is applied to a rat model of stroke, the endothelin-1 model of focal cortical ischemia. METHODS: We intended to track endogenous neuroblast migration from the subventricular zone to the stroke area using previously described methods for in vivo labeling of endogenous neuroblasts with MPIOs and following migration with high resolution MRI. RESULTS:MPIOs accumulation in stroke regions of endothelin-1-treated brains involves two dynamic steps: an initial rapid cell independent mechanism, followed by slower MPIOs accumulation. While the latter may in part be attributable to cell dependent delivery of the particles, the cell independent mechanism complicates the interpretation of the data. Strategies aimed at prelabeling the stem cell niche reduced cell independent MPIOs accumulation, but failed to abolish it. CONCLUSION: We conclude that MRI-based neural stem/progenitor cell tracking via direct injection of MPIOs into the lateral and third ventricles, requires significant validation in models of brain disease/trauma.
Authors: Dorela D Shuboni-Mulligan; Shatadru Chakravarty; Christiane L Mallett; Alexander M Wolf; Pauline M Dmitriev; Stacey M Forton; Erik M Shapiro Journal: Neuroimage Date: 2019-05-29 Impact factor: 6.556
Authors: Marina Y Khodanovich; Andrey E Akulov; Tatyana V Anan'ina; Marina S Kudabaeva; Anna O Pishchelko; Elena P Krutenkova; Nikolay M Nemirovich-Danchenko; Mikhail V Svetlik; Yana A Tumentceva; Chris Van den Haute; Rik Gijsbers; Veronique Daniëls; Irina Thiry; Alexandra G Pershina; Maria M Shadrina; Anna V Naumova Journal: Int J Mol Sci Date: 2020-11-25 Impact factor: 5.923
Authors: Marina Y Khodanovich; Tatyana V Anan'ina; Elena P Krutenkova; Andrey E Akulov; Marina S Kudabaeva; Mikhail V Svetlik; Yana A Tumentceva; Maria M Shadrina; Anna V Naumova Journal: Biomedicines Date: 2022-06-30