Journal
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 40, Issue 1_SUPPL, Pages S117-S133Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/0271678X20953913
Keywords
Ischemic stroke; neuroinflammation; microglial; macrophage activation; Iba-1-antibody-conjugated superparamagnetic iron-platinum nanoparticles; magnetic resonance imaging
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Funding
- NIH/NINDS [1R21NS091710]
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Microglial/macrophage activation plays a dual role in response to brain injury after a stroke, promoting early neuroinflammation and benefit for neurovascular recovery. Therefore, the dynamics of stroke-induced cerebral microglial/macrophage activation are of substantial interest. This study used novel anti-Iba-1-targeted superparamagnetic iron-platinum (FePt) nanoparticles in conjunction with magnetic resonance imaging (MRI) to measure the spatiotemporal changes of the microglial/macrophage activation in living rat brain for four weeks post-stroke. Ischemic lesion areas were identified and measured using T-2-weighted MR images. After injection of the FePt-nanoparticles, T-2*-weighted MR images showed that the nanoparticles were seen solely in brain regions that coincided with areas of active microglia/macrophages detected by post-mortem immunohistochemistry. Good agreement in morphological and distributive dynamic changes was also observed between the Fe+-cells and the Iba-1(+)-microglia/macrophages. The spatiotemporal changes of nanoparticle detected by T-2*-weighted images paralleled the changes of microglial/macrophage activation and phenotypes measured by post-mortem immunohistochemistry over the four weeks post-stroke. Maximum microglial/macrophage activation occurred seven days post-stroke for both measures, and the diminished activation found after two weeks continued to four weeks. Our results suggest that nanoparticle-enhanced MRI may constitute a novel approach for monitoring the dynamic development of neuroinflammation in living animals during the progression and treatment of stroke.
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