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

Authors

  • Dorit Granot,

    1. Department of Diagnostic Radiology, Molecular and Cellular MRI Laboratory, Yale University School of Medicine, New Haven, Connecticut, USA
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  • Erik M. Shapiro

    Corresponding author
    1. Department of Diagnostic Radiology, Molecular and Cellular MRI Laboratory, Yale University School of Medicine, New Haven, Connecticut, USA
    2. Department of Radiology, Michigan State University, East Lansing, Michigan, USA
    • Correspondence to: Erik M. Shapiro, Ph.D., Michigan State University, Department of Radiology, 846 Service Rd, East Lansing, MI 48824. E-mail: Erik.Shapiro@radiology.msu.edu

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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. Magn Reson Med 71:1568–1574, 2014. © 2013 Wiley Periodicals, Inc.

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