Feridex preloading permits tracking of CNS-resident macrophages after transient middle cerebral artery occlusion.
At this time, the pathophysiology of macrophage involvement and their role in stroke progression are poorly understood. Recently, T2- and T2*-weighted magnetic resonance imaging (MRI), after intravenous administration of iron-oxide particles, have been used to understand the inflammatory cascade. Earlier studies report that image enhancement after stroke is from iron-laden macrophages; however, they do not account for potential blood-brain barrier disruption and nonspecific contrast enhancement. In this study, spontaneously hypertensive rats were preloaded with Feridex 7 days before stroke, permitting the labeling of bone-marrow-derived macrophages. Three-dimensional gradient-echo imaging showed average signal decreases of 13% to 23% in preloaded animals, concentrated on the lesion periphery and reaching a maximum on days 2 to 4 after stroke. Immunohistochemistry showed ED-2+, PB+, MHC-II+ and TNF-alpha+ perivascular macrophages (PVM), meningeal macrophages (MM), and choroid plexus macrophages (CPM). ED-1+ and IBA+ tissue macrophages and/or activated microglia were located throughout the lesion, but were PB-. These findings indicate the following: (1) Feridex preloading permits tracking of the central nervous system (CNS)-resident macrophages (PVM, MM, and CPM) and (2) CNS-resident macrophages likely play an integral role in the inflammatory cascade through antigen presentation and expression of proinflammatory cytokines. Further refinement of this method should permit noninvasive monitoring of inflammation and potential evaluation of antiinflammatory therapies in preclinical models of stroke.
Section on Stroke Diagnostics and Therapeutics, Stroke Branch, National Institute of Neurological Disorders and Stroke, Building 10, Room B1D733, 10 Center henninge@ninds.nih.gov
Erica C
EC
Henning
Christl A
CA
Ruetzler
Martin R
MR
Gaudinski
Tom C-C
TC
Hu
Lawrence L
LL
Latour
John M
JM
Hallenbeck
Steven
S
Warach
D000818:Animals; D002490:Central Nervous System / Q000276:immunology*; D003287:Contrast Media; D003911:Dextrans; D052203:Ferrosoferric Oxide; D020244:Infarction, Middle Cerebral Artery / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D007501:Iron; D008264:Macrophages / Q000473:pathology / Q000502:physiology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D008297:Male; D008722:Methods; D015336:Molecular Probe Techniques; D010087:Oxides; D051381:Rats; D011918:Rats, Inbred SHR; D020521:Stroke / Q000276:immunology*
D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; D007501:Iron; C065507:ferumoxides; D052203:Ferrosoferric Oxide