Delivery of virus-sized iron oxide particles to rodent cns neurons

Edward A. Neuwelt, Ralph Weissleder, Gajanan Nilaver, Robert A. Kroll, Simon Roman-Goldstein, Jerzy Szumowski, Michael A. Pagel, Russell S. Jones, Laura G. Remsen, Christopher I. Mccormick, Eva M. Shannon, Leslie L. Muldoon

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

DELIVERY OF VIRAL particles to the brain is limited by the volume of distribution that can be obtained. Additionally, there is currently no way to non-invasively monitor the distribution of virus following delivery to the central nervous system (CNS). To examine the delivery of virus-sized particles across the blood-brain barrier (BBB), dextran coated, superparamagnetic monocrystalline iron oxide particles, with a hydrodynamic diameter of 20 ± 4 nm, were delivered to rat brain by direct intracerebral inoculation or by osmotic BBB disruption with hypertonic mannitol. Delivery of these particles was documented by magnetic resonance (MR) imaging and, unexpectedly, neuronal uptake was demonstrated by histochemical staining. Electron microscopy (EM) confirmed iron particle delivery across the capillary basement membrane and localization within CNS parenchymal cells following administration with BBB disruption. This is the first histologic and ultrastructural documentation of the delivery of particles the size of virions across the blood-brain barrier. Additionally, these dextran-coated, iron oxide particles may be useful, in and of themselves, as vectors for diagnostic and/or therapeutic interventions directed at the CNS.

Original languageEnglish (US)
Pages (from-to)777-784
Number of pages8
JournalNeurosurgery
Volume34
Issue number4
DOIs
StatePublished - Apr 1994

Keywords

  • Blood-brain barrier
  • Genetic vectors
  • Iron-dextran complex
  • Magnetic resonance imaging

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

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  • Cite this

    Neuwelt, E. A., Weissleder, R., Nilaver, G., Kroll, R. A., Roman-Goldstein, S., Szumowski, J., Pagel, M. A., Jones, R. S., Remsen, L. G., Mccormick, C. I., Shannon, E. M., & Muldoon, L. L. (1994). Delivery of virus-sized iron oxide particles to rodent cns neurons. Neurosurgery, 34(4), 777-784. https://doi.org/10.1227/00006123-199404000-00048