Transient hypoxia-ischemia in rats: changes in diffusion-sensitive MR imaging findings, extracellular space, and Na+-K+ -adenosine triphosphatase and cytochrome oxidase activity

Radiology. 2002 Apr;223(1):65-75. doi: 10.1148/radiol.2231010736.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diffusion
  • Electron Transport Complex IV / metabolism*
  • Extracellular Space / enzymology*
  • Female
  • Hypoxia-Ischemia, Brain / enzymology*
  • Hypoxia-Ischemia, Brain / pathology*
  • Magnetic Resonance Imaging*
  • Pregnancy
  • Rats
  • Rats, Wistar
  • Sodium-Potassium-Exchanging ATPase / metabolism*


  • Electron Transport Complex IV
  • Sodium-Potassium-Exchanging ATPase