Serial MRI after transient focal cerebral ischemia in rats: dynamics of tissue injury, blood-brain barrier damage, and edema formation.
OBJECTIVE
With the advent of thrombolytic therapy for acute stroke, reperfusion-associated mechanisms of tissue injury have assumed greater importance. In this experimental study, we used several MRI techniques to monitor the dynamics of secondary ischemic damage, blood-brain barrier (BBB) disturbances, and the development of vasogenic edema during the reperfusion phase after focal cerebral ischemia in rats.


METHODS
Nineteen Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion of 30 minutes, 60 minutes, or 2.5 hours with the suture occlusion model. MRI, including diffusion-weighted imaging (DWI), T2-weighted imaging, perfusion-weighted imaging, and T1-weighted imaging, was performed 5 to 15 minutes before reperfusion, as well as 0.5, 1.5, and 2.5 hours and 1, 2, and 7 days after withdrawal of the suture. Final infarct size was determined histologically at 7 days.


RESULTS
In the 30-minute ischemia group (and partially also after 60 minutes), DWI abnormalities reversed transiently during the early reperfusion period but recurred after 1 day, probably due to secondary ischemic damage. After 2.5 hours of ischemia, DWI abnormalities no longer reversed, and signal intensity on both DWI and T2-weighted images increased rapidly in the previously ischemic region due to BBB damage (enhancement on postcontrast T1-weighted images) and edema formation. Early BBB damage during reperfusion was found to be predictive of relatively pronounced edema at subacute time points and was probably related to the increased mortality rates in this experimental group (3 of 7).


CONCLUSIONS
Reperfusion after short periods of ischemia (30 to 60 minutes) appears to be mainly complicated by secondary ischemic damage as shown by the delayed recurrence of the DWI lesions, whereas BBB damage associated with vasogenic edema becomes a dominant factor with longer occlusion times (2.5 hours).
Department of Radiology, Lucas MRS/MRI Center, Stanford Stroke Center, Stanford University, CA, USA. tnh@rz.uni-frankfurt.de
T
T
Neumann-Haefelin
A
A
Kastrup
A
A
de Crespigny
M A
MA
Yenari
T
T
Ringer
G H
GH
Sun
M E
ME
Moseley
D000818:Animals; D001479:Basal Ganglia / Q000098:blood supply / Q000473:pathology*; D001812:Blood-Brain Barrier; D001929:Brain Edema / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D002560:Cerebrovascular Circulation; D002546:Ischemic Attack, Transient / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012008:Recurrence; D015427:Reperfusion Injury / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism; D013702:Temporal Lobe / Q000098:blood supply / Q000473:pathology*