title: Iron oxide magnetic nanoparticles highlight early involvement of the choroid plexus in central nervous system inflammation.
abstract: Neuroinflammation during multiple sclerosis involves immune cell infiltration and disruption of the BBB (blood-brain barrier). Both processes can be visualized by MRI (magnetic resonance imaging), in multiple sclerosis patients and in the animal model EAE (experimental autoimmune encephalomyelitis). We previously showed that VSOPs (very small superparamagnetic iron oxide particles) reveal CNS (central nervous system) lesions in EAE which are not detectable by conventional contrast agents in MRI. We hypothesized that VSOP may help detect early, subtle inflammatory events that would otherwise remain imperceptible. To investigate the capacity of VSOP to reveal early events in CNS inflammation, we induced EAE in SJL mice using encephalitogenic T-cells, and administered VSOP prior to onset of clinical symptoms. In parallel, we administered VSOP to mice at peak disease, and to unmanipulated controls. We examined the distribution of VSOP in the CNS by MRI and histology. Prior to disease onset, in asymptomatic mice, VSOP accumulated in the choroid plexus and in spinal cord meninges in the absence of overt inflammation. However, VSOP was undetectable in the CNS of non-immunized control mice. At peak disease, VSOP was broadly distributed; we observed particles in perivascular inflammatory lesions with apparently preserved glia limitans. Moreover, at peak disease, VSOP was prominent in the choroid plexus and was seen in elongated endothelial structures, co-localized with phagocytes, and diffusely disseminated in the parenchyma, suggesting multiple entry mechanisms of VSOP into the CNS. Thus, using VSOP we were able to discriminate between inflammatory events occurring in established EAE and, importantly, we identified CNS alterations that appear to precede immune cell infiltration and clinical onset.
authors: Institute for Medical Immunology, Charité-Universtitätsmedizin Berlin, Berlin, Germany.
authors: Jason M
authors: JM
authors: Millward
authors: Jörg
authors: J
authors: Schnorr
authors: Matthias
authors: M
authors: Taupitz
authors: Susanne
authors: S
authors: Wagner
authors: Jens T
authors: JT
authors: Wuerfel
authors: Carmen
authors: C
authors: Infante-Duarte
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002490:Central Nervous System / Q000276:immunology / Q000473:pathology*; D002831:Choroid Plexus; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology*; D005260:Female; D005620:Freund's Adjuvant / Q000633:toxicity; D019786:Gadolinium DTPA; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D018991:Myelin Proteolipid Protein / Q000633:toxicity; D053758:Nanoparticles; D010446:Peptide Fragments / Q000633:toxicity
chemical_list: C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D007797:Laminin; D008840:Microfilament Proteins; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; C435023:myelin proteolipid protein (139-151); D005620:Freund's Adjuvant; D019786:Gadolinium DTPA