Trafficking of superparamagnetic iron oxide particles (Combidex) from brain to lymph nodes in the rat

Leslie Muldoon, P. Varallyay, Dale Kraemer, G. Kiwic, K. Pinkston, S. L. Walker-Rosenfeld, Edward Neuwelt

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Central nervous system (CNS) drainage may occur via connections to the vasculature, but in animal models up to 50% occurs via perivascular, perineural and primitive lymphatic drainage to cervical lymph nodes. We evaluated efflux of particles from the brain to cervical lymph nodes in normal rats, using Combidex iron oxide-based magnetic resonance imaging (MRI) agent. After intracerebral, intraventricular, intracarotid or intravenous injection of Combidex in normal Long Evans rats, particle localization was assessed by MRI and histochemistry for iron and the dextran coat (n = 27). Intraventricular or intracerebral injection, but not intracarotid administration of Combidex (100 μg), resulted in MRI signal changes in the deep cervical lymph nodes around the carotid artery, and, less strongly, in the superficial cervical nodes. Within 2 h of Combidex administration, iron was histologically localized in cervical lymph nodes, with patched staining of capsule and peripheral sinus consistent with delivery via multiple afferent lymphatic vessels. Lymph node staining in groups receiving CNS Combidex was significantly different from controls (P <0.0001) and was significantly localized in the deep vs. superficial cervical lymph nodes (P = 0.0003). The trafficking of the superparamagnetic iron particles from the CNS in the rat could be visualized by MRI and histology. Combidex provides a powerful tool to rapidly assess drainage of virus-sized particles from the CNS.

Original languageEnglish (US)
Pages (from-to)70-79
Number of pages10
JournalNeuropathology and Applied Neurobiology
Volume30
Issue number1
DOIs
StatePublished - Feb 2004

Fingerprint

Lymph Nodes
Brain
Central Nervous System
Magnetic Resonance Imaging
Drainage
Iron
Staining and Labeling
Intraventricular Injections
Long Evans Rats
Lymphatic Vessels
Dextrans
Carotid Arteries
Intravenous Injections
Virion
Capsules
ferric oxide
ferumoxtran-10
Histology
Animal Models
Injections

Keywords

  • Animal model
  • Blood-brain barrier
  • Cerebrospinal fluid
  • Cervical lymphatics
  • Combidex
  • Lymph nodes
  • Magnetic resonance imaging

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Trafficking of superparamagnetic iron oxide particles (Combidex) from brain to lymph nodes in the rat. / Muldoon, Leslie; Varallyay, P.; Kraemer, Dale; Kiwic, G.; Pinkston, K.; Walker-Rosenfeld, S. L.; Neuwelt, Edward.

In: Neuropathology and Applied Neurobiology, Vol. 30, No. 1, 02.2004, p. 70-79.

Research output: Contribution to journalArticle

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