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Transient Hypoxia-Ischemia in Rats: Changes in Diffusion-Sensitive MR Imaging Findings, Extracellular Space, and Na⁺-K⁺–Adenosine Triphosphatase and Cytochrome Oxidase Activity¹

¹ From the Institute for Biodiagnostics, National Research Council Canada, Winnipeg, Manitoba (M.Q., K.L.M., U.I.T.); and Department of Pathology, University of Manitoba, Winnipeg, Canada (M.R.D.B.). Received April 10, 2001; revision requested May 11; revision received August 2; accepted September 7. Supported by grant FRN-15635 from the Canadian Institutes for Health Research. Address correspondence to U.I.T., Institute for Biodiagnostics (West), National Research Council, 3330 Hospital Dr NW, Calgary, Alberta, Canada T2N 4N1 (e-mail: ursula.tuor@nrc.ca).

PURPOSE: To investigate the correlation between diffusion-weighted (DW) magnetic resonance (MR) image changes with alterations in extracellular volume and changes in cytochrome oxidase and Na⁺-K⁺–adenosine triphosphatase (ATPase) activity at various times during and after cerebral hypoxia-ischemia in neonatal and juvenile rats.

MATERIALS AND METHODS: One– and 4-week-old rats were randomly assigned to control or transient cerebral hypoxia-ischemia (ie, right carotid artery occlusion plus exposure to 8% oxygen) groups. Hypoxic-ischemic changes compared with normal ipsilateral brain tissue on DW images and the apparent diffusion coefficient of water were measured during and at 1 and 24 hours after hypoxia-ischemia ended. Hypoxic-ischemic changes in extracellular space and ipsilateral versus contralateral differences in Na⁺-K⁺–ATPase and cytochrome oxidase activity were measured.

RESULTS: Hyperintensities on DW images obtained during hypoxia-ischemia correlated well (P < .05) with extracellular space reductions, which occurred 15 minutes earlier in the brains of 4-week-old rats than in the brains of 1-week-old rats. Similarly, within 1 hour after hypoxia-ischemia ended, DW image and extracellular space changes normalized. In contrast, Na⁺-K⁺–ATPase and cytochrome oxidase activity decreased in some regions during hypoxia-ischemia and remained reduced 1 hour after the end of hypoxia-ischemia. Twenty-four hours after signal intensity normalization, hyperintense areas reappeared on DW images, and Na⁺-K⁺–ATPase and cytochrome oxidase activity remained decreased.

CONCLUSION: Signal intensity alterations with diffusion-sensitive MR imaging during and after transient hypoxia-ischemia are closely associated with a corresponding shrinkage and reexpansion of the extracellular space, irrespective of age. Mechanisms other than Na⁺-K⁺–ATPase changes may induce the early cell volume changes detected with diffusion-sensitive MR imaging.

© RSNA, 2002

Index terms: Animals • Brain, ischemia, 10.781 • Brain, MR, 10.121411, 10.12144 • Magnetic resonance (MR), diffusion study, 10.121411, 10.12144

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