Histochemical detection of ultrasmall superparamagnetic iron oxide (USPIO) contrast medium uptake in experimental brain ischemia.
Recently, macrophage infiltration in different central nervous system (CNS) pathologies has been visualized with ultrasmall particles of iron oxide (USPIO) as a new cell-specific contrast medium for MRI. However, validation of these findings at the histological level has been hampered by the fact that the in situ detection of iron uptake by conventional Prussian blue staining is not sensitive enough to detect low amounts of iron in the brain. Here, an improved method for the histochemical detection of USPIO uptake in ischemic brain lesions is reported. The procedure relies on the sequential enhancement of Prussian blue staining by diaminobenzidine and silver/gold impregnation. After photothrombotic cortical brain infarction, this method allowed sensitive in situ detection of iron-laden macrophages which matched both macrophage immunostaining and USPIO-induced signal alterations in high-resolution 7 T MRI. This staining method provides a basis for correlative histological assessment of USPIO-enhanced MRI in a broad spectrum of CNS pathologies.
Schroeter
Michael
M
Department of Neurology, Heinrich Heine University, Duesseldorf, Germany. schroetm@uni-duesseldorf.de
Saleh
Andreas
A
Wiedermann
Dirk
D
Hoehn
Mathias
M
Jander
Sebastian
S
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D003287:Contrast Media / Q000493:pharmacokinetics*; D003911:Dextrans; D052203:Ferrosoferric Oxide; D007150:Immunohistochemistry; D007501:Iron / Q000493:pharmacokinetics*; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D010087:Oxides / Q000493:pharmacokinetics*; D051381:Rats; D013154:Spleen / Q000378:metabolism*; D013194:Staining and Labeling
D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; C097921:ferumoxtran-10; D007501:Iron; D052203:Ferrosoferric Oxide