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

Edward 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 Muldoon

Research output: Contribution to journalArticle

77 Citations (Scopus)

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
StatePublished - 1994

Fingerprint

Blood-Brain Barrier
Rodentia
Viruses
Neurons
Central Nervous System
Virion
Brain
Mannitol
Hydrodynamics
Dextrans
Particle Size
Basement Membrane
Documentation
Electron Microscopy
Iron
Magnetic Resonance Imaging
Staining and Labeling
ferric oxide
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

Cite this

Neuwelt, E., Weissleder, R., Nilaver, G., Kroll, R. A., Roman-Goldstein, S., Szumowski, J., ... Muldoon, L. (1994). Delivery of virus-sized iron oxide particles to rodent cns neurons. Neurosurgery, 34(4), 777-784.

Delivery of virus-sized iron oxide particles to rodent cns neurons. / Neuwelt, Edward; Weissleder, Ralph; Nilaver, Gajanan; Kroll, Robert A.; Roman-Goldstein, Simon; Szumowski, Jerzy; Pagel, Michael A.; Jones, Russell S.; Remsen, Laura G.; Mccormick, Christopher I.; Shannon, Eva M.; Muldoon, Leslie.

In: Neurosurgery, Vol. 34, No. 4, 1994, p. 777-784.

Research output: Contribution to journalArticle

Neuwelt, E, Weissleder, R, Nilaver, G, Kroll, RA, Roman-Goldstein, S, Szumowski, J, Pagel, MA, Jones, RS, Remsen, LG, Mccormick, CI, Shannon, EM & Muldoon, L 1994, 'Delivery of virus-sized iron oxide particles to rodent cns neurons', Neurosurgery, vol. 34, no. 4, pp. 777-784.
Neuwelt E, Weissleder R, Nilaver G, Kroll RA, Roman-Goldstein S, Szumowski J et al. Delivery of virus-sized iron oxide particles to rodent cns neurons. Neurosurgery. 1994;34(4):777-784.
Neuwelt, Edward ; Weissleder, Ralph ; Nilaver, Gajanan ; Kroll, Robert A. ; Roman-Goldstein, Simon ; Szumowski, Jerzy ; Pagel, Michael A. ; Jones, Russell S. ; Remsen, Laura G. ; Mccormick, Christopher I. ; Shannon, Eva M. ; Muldoon, Leslie. / Delivery of virus-sized iron oxide particles to rodent cns neurons. In: Neurosurgery. 1994 ; Vol. 34, No. 4. pp. 777-784.
@article{d5143934fea54374bef3059110fb2a63,
title = "Delivery of virus-sized iron oxide particles to rodent cns neurons",
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.",
keywords = "Blood-brain barrier, Genetic vectors, Iron-dextran complex, Magnetic resonance imaging",
author = "Edward Neuwelt and Ralph Weissleder and Gajanan Nilaver and Kroll, {Robert A.} and Simon Roman-Goldstein and Jerzy Szumowski and Pagel, {Michael A.} and Jones, {Russell S.} and Remsen, {Laura G.} and Mccormick, {Christopher I.} and Shannon, {Eva M.} and Leslie Muldoon",
year = "1994",
language = "English (US)",
volume = "34",
pages = "777--784",
journal = "Neurosurgery",
issn = "0148-396X",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Delivery of virus-sized iron oxide particles to rodent cns neurons

AU - Neuwelt, Edward

AU - Weissleder, Ralph

AU - Nilaver, Gajanan

AU - Kroll, Robert A.

AU - Roman-Goldstein, Simon

AU - Szumowski, Jerzy

AU - Pagel, Michael A.

AU - Jones, Russell S.

AU - Remsen, Laura G.

AU - Mccormick, Christopher I.

AU - Shannon, Eva M.

AU - Muldoon, Leslie

PY - 1994

Y1 - 1994

N2 - 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.

AB - 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.

KW - Blood-brain barrier

KW - Genetic vectors

KW - Iron-dextran complex

KW - Magnetic resonance imaging

UR - http://www.scopus.com/inward/record.url?scp=0028344580&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028344580&partnerID=8YFLogxK

M3 - Article

VL - 34

SP - 777

EP - 784

JO - Neurosurgery

JF - Neurosurgery

SN - 0148-396X

IS - 4

ER -