in Vivo Monitoring of Macrophage Infiltration in Experimental Ischemic Brain Lesions by Magnetic Resonance Imaging

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Abstract
Although macrophages represent the major inflammatory cells in cerebral ischemia, the kinetics of macrophage infiltration are largely unknown. To address this issue, we injected superparamagnetic iron oxide (SPIO) particles into the circulation of rats at different time points after focal photothrombotic cerebral infarction and performed magnetic resonance imaging (MRI) 24 hours later. Infarcts appeared as hyperintense lesions on T2-w and CISS MR images during all stages. At days 5.5 and 6, an additional rim of signal loss indicative of local accumulation of SPIO particles appeared at the outer margin of the hyperintense ischemic lesions, which was not present at days 1 to 5. Areas of signal loss corresponded to local accumulation of iron-loaded macrophages in histologic sections. At day 8, signal loss became restricted to the inner core of the lesions and ceased thereafter. Macrophages, however, were still present in late ischemic brain lesions, but they were iron-negative. Thus SPIO-induced signal loss indicates active macrophage transmigration into ischemic infarcts but not their mere presence. SPIO-induced signal loss was independent from the disturbance of the blood-brain barrier. In conclusion, we have shown by in vivo monitoring that macrophages enter photothrombotic infarcts at late stages of infarct development, suggesting a role in tissue remodeling rather than neuronal injury.