Progression of a focal ischemic lesion in rat brain during treatment with a novel glycine/NMDA antagonist: an in vivo three-dimensional diffusion-weighted MR microscopy study.
Stroke was induced in two groups of anesthetized rats by occlusion of the middle cerebral artery (MCA) and ipsilateral common carotid artery. Group 1 (control) received vehicle and group 2 received the glycine N-methyl-D-aspartate (NMDA) antagonist ZD9379. Stroke volume was assessed by three-dimensional diffusion-weighted MR microscopy at 2.5 and 6 hours of MCA occlusion. At 2.5 hours, stroke volumes were identical in the two groups. At 6 hours, stroke volumes had increased by 15% in the control group; in contrast, the treated group showed a 40% reduced stroke volume. Conclusions from this in vivo study were as follows: (a) our technique allows more efficient and accurate measurement of stroke volume with an improvement in resolution over a previous method; (b) the ability to measure stroke volume at multiple time points shows volume change and assessment of time dependency of drug treatment; (c) at 6 hours, the glycine antagonist ZD9379 reduced stroke volume by 40%.
Qiu
H
H
Center for In Vivo Microscopy, Duke University Medical Center, Durham, NC 27710, USA.
Hedlund
L W
LW
Gewalt
S L
SL
Benveniste
H
H
Bare
T M
TM
Johnson
G A
GA
D000818:Animals; D001921:Brain / Q000473:pathology*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D011724:Pyridazines / Q000627:therapeutic use*; D011804:Quinolines / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors*; D013997:Time Factors
D011724:Pyridazines; D011804:Quinolines; D018009:Receptors, Glycine; C106383:ZD 9379