Analysis of lesion development during acute inflammation and remission in a rat model of experimental autoimmune encephalomyelitis by visualization of macrophage infiltration, demyelination and blood-brain barrier damage.
In vivo tracking of macrophage migration is feasible by labeling cells with ultra-small particles of iron oxide (USPIO). It is demonstrated that it is possible to monitor distinct patterns of macrophage migration during the early states of inflammation in a rodent model of chronic relapsing experimental autoimmune encephalomyelitis (EAE). As previous MRI studies showed that EAE inflammation processes are clearly linked to macrophage infiltration in the brain, a longitudinal protocol for macrophage visualization was designed, where USPIOs were injected repeatedly during the acute phase of the disease, the remitting phase and the first relapse. In addition to USPIO-enhanced MRI, blood-brain barrier (BBB) damage, magnetization transfer ratios (MTRs) and neurological impairment were assessed as classical markers for central nervous system (CNS) inflammation and tissue damage. During the acute phase, animals showed severe paralysis of the hind paws, intense accumulation of macrophages in brain tissue and some diffuse patterns of BBB disruption. While USPIO-accumulation completely disappeared after the acute phase, residual damage of the BBB remained detectable in some lesions during the remitting phase. During the first relapse, the accumulation of USPIO-loaded cells was less pronounced but still detectable. The time course of MTR, which is used as a marker for myelin loss, was linked to the infiltration of macrophages during the acute phase.
Berger
Cedric
C
Novartis Institutes for Biomedical Research, CH-4002 Basel, Switzerland.
Hiestand
Peter
P
Kindler-Baumann
Diana
D
Rudin
Markus
M
Rausch
Martin
M
D000208:Acute Disease; D000818:Animals; D001812:Blood-Brain Barrier / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D002465:Cell Movement; D003287:Contrast Media; D003911:Dextrans; D004195:Disease Models, Animal; D018450:Disease Progression; D004660:Encephalitis / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology*; D005260:Female; D052203:Ferrosoferric Oxide; D007089:Image Enhancement / Q000379:methods; D007501:Iron; D008264:Macrophages / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D010087:Oxides; D051381:Rats; D011917:Rats, Inbred Lew; D012075:Remission, Spontaneous
D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; C097921:ferumoxtran-10; D007501:Iron; D052203:Ferrosoferric Oxide