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


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.


CONCLUSIONS
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.
Qiao
Min
M
Institute for Biodiagnostics, National Research Council Canada, Winnipeg, Manitoba.
Malisza
Krisztina L
KL
Del Bigio
Marc R
MR
Tuor
Ursula I
UI
D000818:Animals; D004058:Diffusion; D003576:Electron Transport Complex IV / Q000378:metabolism*; D005110:Extracellular Space / Q000201:enzymology*; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000201:enzymology* / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D003576:Electron Transport Complex IV; D000254:Sodium-Potassium-Exchanging ATPase