Background and Purpose—
The ischemic penumbra is a major focus of stroke research.
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F-fluoromisonidazole (
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F-FMISO), a positron emission tomography (PET) marker of hypoxic cells, has shown promise as a technique to image the penumbra in humans. Our aim was to delineate the pattern of
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F-FMISO binding in a rat middle cerebral artery transient thread-occlusion model, and correlate this with tissue outcome at 24 hours. We hypothesized that the pattern of
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F-FMISO binding would mimic that seen in humans.
Methods—
Thirty-eight rats underwent 2 hours transient middle cerebral artery (MCA) occlusion, and then received
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F-FMISO at time points from 0.5 to 22 hours post-MCA occlusion and were killed 2 hours later. Autoradiographic assessment of
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F-FMISO binding and assessment (triphenyltetrazolium chloride) of the area of infarction were performed on tissue slices.
Results—
Until 1 hour after MCA occlusion,
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F-FMISO binding was increased in the entire MCA territory, with little or no infarction visible. Over the next 5 hours, the pattern of binding evolved to a small rim of intensely binding tissue surrounding the infarct core, which itself showed reduced binding compared with the contralateral hemisphere. By 24 hours, there was minimal accumulation of
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F-FMISO binding and a large area of infarction.
Conclusions—
The pattern of
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F-FMISO binding rats reproduced the pattern seen in humans, consistent with this tracer being a marker of the ischemic penumbra in both species. This technique may have application in studying the ischemic penumbra in animal models, and correlating this with similar studies in humans.
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