Feridex preloading permits tracking of CNS-resident macrophages after transient middle cerebral artery occlusion

Erica C. Henning, Christl A. Ruetzler, Martin R. Gaudinski, Tom C C Hu, Lawrence L. Latour, John M. Hallenbeck, Steven Warach

Research output: Contribution to journalArticle

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Abstract

At this time, the pathophysiology of macrophage involvement and their role in stroke progression are poorly understood. Recently, T 2 - and T 2 -weighted magnetic resonance imaging (MRI), after intravenous administration of iron-oxide particles, have been used to understand the inflammatory cascade. Earlier studies report that image enhancement after stroke is from iron-laden macrophages; however, they do not account for potential blood-brain barrier disruption and nonspecific contrast enhancement. In this study, spontaneously hypertensive rats were preloaded with Feridex 7 days before stroke, permitting the labeling of bone-marrow-derived macrophages. Three-dimensional gradient-echo imaging showed average signal decreases of 13% to 23% in preloaded animals, concentrated on the lesion periphery and reaching a maximum on days 2 to 4 after stroke. Immunohistochemistry showed ED-2 , PB , MHC-II and TNF-α perivascular macrophages (PVM), meningeal macrophages (MM), and choroid plexus macrophages (CPM). ED-1 and IBA tissue macrophages and/or activated microglia were located throughout the lesion, but were PB . These findings indicate the following: (1) Feridex preloading permits tracking of the central nervous system (CNS)-resident macrophages (PVM, MM, and CPM) and (2) CNS-resident macrophages likely play an integral role in the inflammatory cascade through antigen presentation and expression of proinflammatory cytokines. Further refinement of this method should permit noninvasive monitoring of inflammation and potential evaluation of antiinflammatory therapies in preclinical models of stroke.

Original languageEnglish (US)
Pages (from-to)1229-1239
Number of pages11
JournalJournal of Cerebral Blood Flow and Metabolism
Volume29
Issue number7
DOIs
StatePublished - Jul 2009

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Middle Cerebral Artery Infarction
Central Nervous System
Macrophages
Stroke
Choroid Plexus
ferumoxides
Image Enhancement
Antigen Presentation
Microglia
Inbred SHR Rats
Blood-Brain Barrier
Intravenous Administration
Anti-Inflammatory Agents
Iron
Immunohistochemistry
Magnetic Resonance Imaging
Cytokines

Keywords

  • Feridex
  • Inflammation
  • Macrophages
  • MRI
  • Stroke

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Neurology

Cite this

Henning, E. C., Ruetzler, C. A., Gaudinski, M. R., Hu, T. C. C., Latour, L. L., Hallenbeck, J. M., & Warach, S. (2009). Feridex preloading permits tracking of CNS-resident macrophages after transient middle cerebral artery occlusion. Journal of Cerebral Blood Flow and Metabolism, 29(7), 1229-1239. https://doi.org/10.1038/jcbfm.2009.48

Feridex preloading permits tracking of CNS-resident macrophages after transient middle cerebral artery occlusion. / Henning, Erica C.; Ruetzler, Christl A.; Gaudinski, Martin R.; Hu, Tom C C; Latour, Lawrence L.; Hallenbeck, John M.; Warach, Steven.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 29, No. 7, 07.2009, p. 1229-1239.

Research output: Contribution to journalArticle

Henning, EC, Ruetzler, CA, Gaudinski, MR, Hu, TCC, Latour, LL, Hallenbeck, JM & Warach, S 2009, 'Feridex preloading permits tracking of CNS-resident macrophages after transient middle cerebral artery occlusion', Journal of Cerebral Blood Flow and Metabolism, vol. 29, no. 7, pp. 1229-1239. https://doi.org/10.1038/jcbfm.2009.48
Henning, Erica C. ; Ruetzler, Christl A. ; Gaudinski, Martin R. ; Hu, Tom C C ; Latour, Lawrence L. ; Hallenbeck, John M. ; Warach, Steven. / Feridex preloading permits tracking of CNS-resident macrophages after transient middle cerebral artery occlusion. In: Journal of Cerebral Blood Flow and Metabolism. 2009 ; Vol. 29, No. 7. pp. 1229-1239.
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