title: Ferumoxytol administration does not alter infarct volume or the inflammatory response to stroke in mice.
abstract: Ferumoxytol is an ultrasmall superparamagnetic iron oxide (USPIO) nanoparticle that is FDA-approved as an intravenous iron replacement therapy for the treatment of iron deficiency anemia in patients with chronic kidney disease. Ferumoxytol has also been used as a contrast agent for cerebral blood volume mapping by magnetic resonance imaging (MRI), which suggests it could be used for imaging hemodynamic abnormalities after stroke. However, circulating macrophages can internalize USPIOs, and recent data indicate that the accumulation of iron in macrophages can lead them to adopt the M1 pro-inflammatory phenotype. Therefore, the uptake of intravenously administered iron particles by circulating macrophages that home to the stroke core could potentially alter the inflammatory response to stroke. To test this possibility in vivo we administered a dose of ferumoxytol previously used to obtain cerebral blood volume maps in healthy humans by steady-state susceptibility contrast (SSC) MRI to BALB/cJ mice 48h after stroke and examined cytokine levels, microglial/macrophage activation, and lesion volume in the brain 5 days later. Treatment with ferumoxytol did not lead to any differences in these parameters. These data indicate that the use of ferumoxytol as a contrast agent for brain imaging after stroke does not alter the inflammatory response to stroke in mice, and is therefore unlikely to do so in human subjects.
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA; Department of Immunobiology, Department of Neurology, and the Arizona Center on Aging, University of Arizona, Tucson, AZ, USA.
authors.forename: Kristian P
authors.initials: KP
authors.lastname: Doyle
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Lisa N
authors.initials: LN
authors.lastname: Quach
authors.affiliation: Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Helen E D'
authors.initials: HE
authors.lastname: Arceuil
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA; Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: marion.buckwalter@stanford.edu.
authors.forename: Marion S
authors.initials: MS
authors.lastname: Buckwalter
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D020520:Brain Infarction / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D003287:Contrast Media / Q000633:toxicity*; D016207:Cytokines / Q000378:metabolism; D052203:Ferrosoferric Oxide / Q000633:toxicity*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism; D020521:Stroke / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D003287:Contrast Media; D016207:Cytokines; D052203:Ferrosoferric Oxide; D007501:Iron; C539355:CD68 protein, rat; D000097382:CD68 Molecule
keywords: Ferumoxytol; Inflammation; Magnetic resonance imaging; Stroke