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Department of Neurology (Drs. Minematsu and Fisher), The Medical Center of Central Massachusetts; the Departments of Neurology (Dr. Fisher) and Radiology (Drs. Fisher, Davis, and Sotak), University of Massachusetts Medical School; the Department of Biomedical Engineering (Drs. Li and Sotak), Worcester Polytechnic Institute, Worcester, MA and Cambridge Neuroscience Inc. (Drs. Knapp, Cotter. and McBurney), Cambridge, MA.
We employed diffusion-weighted MRI (DWI) to identify regions of focal brain ischemia during the first 3 hours after permanent occlusion of the middle cerebral artery in rats. Using DWI as early as 30 minutes after the onset of ischemia, it was possible to identify the areas of brain destined to progress to infarction over the next 24 hours in untreated animals, as demonstrated by postmortem evaluation. DWT studies revealed the cerebroprotective effects of a noncompetitive N-methyl-D-aspartate receptor antagonist, CNS 1102, administered 15 minutes postocclusion, both on the cortical and caudoputaminal regions during the initial 3 hours of ischemia. Although the treatment effect lessened over the next 21 hours in a few animals with lower plasma drug levels at 3 hours, postmortem studies demonstrated a 66% reduction in the total volume of infarcted tissue with the treatment and confirmed the DWI results. T2-weighted MRT obtained at similar times revealed little or no abnormality. These results suggest that DWI provides a sensitive in vivo measure of focal cerebral ischemic injury and can assess the beneficial effects of cytoprotective therapy. DWI may be useful in the early evaluation of human stroke patients and in monitoring the effects of cerebroprotective therapies in the clinical setting.
Address correspondence and reprint requests to Dr. Kazuo Minematsu, Neurology, The Medical Center of Central Massachusetts, 119 Belmont Street, Worcester, MA 01605.
Supported in part by the Harrington Neurological Research Fund, the University of Massachusetts, Department of Radiology Research Support Fund, and Cambridge Neuroscience Inc.
Drs. Knapp, Cotter, and McBurney have an equity position in Cambridge Neuroscience Inc., which has developed CXS 1102.
Presented in part at the 44th annual meeting of the American Academy of Neurology, San Diego, CA, May 1992.
Received April 28, 1992. Accepted for publication in final form June 18, 1992.
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