Early-stage investigations of ultrasmall superparamagnetic iron oxide-induced signal change after permanent middle cerebral artery occlusion in mice.
OBJECTIVE
MR signal changes after intravenous ultrasmall superparamagnetic iron oxide (USPIO) injection are related to inflammatory cells at the subacute stages after focal cerebral injury. However, at the early stages, the interpretation of USPIO-related MR signal alterations remains controversial. Here, we compared MR signal changes after intravenous USPIO injection with the histological iron and macrophage distribution during the first 24 hours in a rodent model of acute stroke.


METHODS
Multiparametric MRI at 7T and histological USPIO distribution were confronted from 6 to 24 hours after permanent middle cerebral artery occlusion in mice. Blood-brain barrier disruption was assessed using gadolinium MRI and immunoglobulin staining. Prussian blue staining was performed to depict the USPIO brain distribution. USPIO uptake by phagocytes was assessed by immunochemistry on brain tissue, peripheral blood cells, and monocyte cells derived from bone marrow culture.


RESULTS
After USPIO injection, 4 areas of early signal change were observed on every MRI. In all these areas, iron particles were mostly free whether detected in the vascular and cerebrospinal fluid compartments or in the interstitium. Within the first 24 hours, USPIO-loaded cells were not detected in the blood of injured mice or in cultured monocytic cells incubated with USPIO at plasmatic concentration.


CONCLUSIONS
These results suggest that, in this model, early reproducible USPIO-related MR signal changes are mainly caused by passive diffusion of free USPIO after blood-brain barrier leakage and by intravascular trapping rather than by peripheral phagocyte infiltration.
Desestret
Virginie
V
Université Lyon, Lyon, France.
Brisset
Jean-Christophe
JC
Moucharrafie
Samir
S
Devillard
Emilie
E
Nataf
Serge
S
Honnorat
Jérôme
J
Nighoghossian
Norbert
N
Berthezène
Yves
Y
Wiart
Marlène
M
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000473:pathology*; D001854:Bone Marrow Cells / Q000502:physiology; D002552:Cerebral Ventricles / Q000473:pathology; D004396:Coloring Agents; D003287:Contrast Media; D003337:Corpus Callosum / Q000473:pathology; D003911:Dextrans; D004578:Electron Spin Resonance Spectroscopy; D005290:Ferric Compounds / Q000008:administration & dosage; D052203:Ferrosoferric Oxide; D005434:Flow Cytometry; D006624:Hippocampus / Q000473:pathology; D007136:Immunoglobulins / Q000737:chemistry; D007150:Immunohistochemistry; D007275:Injections, Intravenous; D007501:Iron; D002546:Ischemic Attack, Transient / Q000473:pathology; D008264:Macrophages / Q000187:drug effects; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D008297:Male; D051379:Mice; D020768:Middle Cerebral Artery / Q000473:pathology*; D009000:Monocytes / Q000187:drug effects; D010087:Oxides; D010587:Phagocytosis
D004396:Coloring Agents; D003287:Contrast Media; D003911:Dextrans; D005290:Ferric Compounds; D007136:Immunoglobulins; D058185:Magnetite Nanoparticles; D010087:Oxides; C097921:ferumoxtran-10; C000499:ferric oxide; D007501:Iron; D052203:Ferrosoferric Oxide