Accumulation of micron sized iron oxide particles in endothelin-1 induced focal cortical ischemia in rats is independent of cell migration

Dorit Granot, Erik M. Shapiro

    Research output: Contribution to journalArticle

    • 4 Citations

    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.

    Original languageEnglish (US)
    Pages (from-to)1568-1574
    Number of pages7
    JournalMagnetic Resonance in Medicine
    Volume71
    Issue number4
    DOIs
    StatePublished - 2014

    Profile

    Endothelin-1
    Oxides
    Cell Movement
    Ischemia
    Iron
    Stem Cells
    Lateral Ventricles
    Brain
    Cell Tracking
    Stem Cell Niche
    Third Ventricle
    Neural Stem Cells
    Neurogenesis
    Brain Diseases
    Brain Injuries
    Rodentia

    Keywords

    • iron oxide
    • neurogenesis
    • stroke

    ASJC Scopus subject areas

    • Radiology Nuclear Medicine and imaging

    Cite this

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    title = "Accumulation of micron sized iron oxide particles in endothelin-1 induced focal cortical ischemia in rats is independent of cell migration",
    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.",
    keywords = "iron oxide, neurogenesis, stroke",
    author = "Dorit Granot and Shapiro, {Erik M.}",
    year = "2014",
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    AU - Shapiro,Erik M.

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    N2 - 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.

    AB - 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.

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