MRI detection of secondary damage after stroke: chronic iron accumulation in the thalamus of the rat brain.
OBJECTIVE
Iron plays a central role in many metabolic processes. Under certain pathological situations it accumulates, producing negative effects such as increasing damage by oxidative stress. The present study examined long-term iron accumulation in a stroke model with secondary degeneration, using MRI and histological techniques.


METHODS
Male Wistar rats (n=22) were subjected to 60 minutes MCA occlusion. MR images (T2- and T2*-weighted) were obtained weekly between weeks 1 and 7 after reperfusion, and at weeks 10, 14, 20, and 24. Histological iron detection and immunohistochemical examination for different markers (NeuN, GFAP, OX-42, HO-1, and APP) were performed at the 3 survival time points (3, 7, and 24 weeks).


RESULTS
Infarcts affecting MCA territory were evident on T2-weighted imaging, and all animals showed deficits on behavioral tests. In the thalamus, T2 hyperintensity was detected 3 weeks after stroke, and disappeared around week 7 when T2*-weighted images showed a marked hypointensity in that area. Histology revealed neuronal loss in the thalamus, accompanied by strong microglial reactivity and microglial HO-1 expression. APP deposits were detected in the thalamus from week 3 on and persisted until week 24. Iron storage was detected in microglia at week 3, in the parenchyma at week 7, and around APP deposits at week 24.


CONCLUSIONS
T2*-weighted MRI allows the detection of secondary damage in the thalamus after MCAO. Iron accumulation in the thalamus is mediated by HO-1 expression in reactive microglia.
Justicia
Carles
C
In-vivo-NMR-Laboratory, Max-Planck-Institute for Neurological Research, Gleuelerstrasse 50, D-50931 Cologne, Germany.
Ramos-Cabrer
Pedro
P
Hoehn
Mathias
M
D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001931:Brain Mapping; D004195:Disease Models, Animal; D005911:Gliosis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D019189:Iron Metabolism Disorders / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D017628:Microglia / Q000166:cytology / Q000378:metabolism; D009410:Nerve Degeneration / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D013786:Thalamic Diseases / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D013788:Thalamus / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*
D015415:Biomarkers; D007501:Iron; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1