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(Stroke. 2008;39:1541.)
© 2008 American Heart Association, Inc.

Original Contributions

MRI Detection of Secondary Damage After Stroke

Chronic Iron Accumulation in the Thalamus of the Rat Brain

Carles Justicia, PhD; Pedro Ramos-Cabrer, PhD Mathias Hoehn, PhD

From the In-vivo-NMR-Laboratory (C.J., P.R.-C., M.H.), Max Planck Institute for Neurological Research, Cologne, Germany; Brain Ischemia and Neurodegeneration (C.J.), IIBB-CSIC, IDIBAPS, Barcelona, Spain; and Clinical Neurosciences Research Laboratory (P.R.-C.), Hospital Clínico Universitario, Santiago de Compostela, Spain.

Correspondence to Prof Dr Mathias Hoehn, In-vivo-NMR-Laboratory, Max-Planck-Institute for Neurological Research, Gleuelerstrasse 50, D-50931 Cologne, Germany. E-mail mathias{at}nf.mpg.de

Background and Purpose— 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.

Key Words: transient cerebral ischemia • thalamus • magnetic resonance imaging • iron • heme-oxigenase-1