The protective effect of MK-801 on infarct development over a period of 24 h as assessed by diffusion-weighted magnetic resonance imaging.
Diffusion-weighted MRI has been used to investigate therapeutic intervention with MK-801 in an animal model of permanent focal cerebral ischaemia. The animals were imaged continuously for 4 h and again at 24 h following occlusion of the middle cerebral artery (MCA) allowing the development of the ischaemic lesion to be monitored continuously in the same animals. An increased DWI signal, seen as a region of hyperintensity, was detected 1 h after MCA-occlusion in the lateral cortex and caudate nucleus in both control and MK-801 (administered at a dose of 3 mg/kg i.p. 5 min post-ischaemia) treated animals. However, the volume of hemispheric and cortical hyperintensity was smaller in the MK-801-treated animals. The area of hyperintensity progressively increased in the control group over the 4 h imaging time and there was also an increase in the area of hyperintensity between 4 and 24 h. At these time points the area of hyperintensity encompassed the dorsolateral cortex and caudate nucleus. MK-801 treated animals also demonstrated some progressive increase in the area of hyperintensity between 1 and 3 h, but no significant increase in the area of hyperintensity was seen after this time. The hyperintense regions at 4 and 24 h were restricted to the so-called 'core areas' of the lesion in MK-801-treated animals. Thus, using DWI the tissue 'at risk' following ischaemia could be identified and the protective effect of therapeutic intervention demonstrated.
Gill
R
R
Department of Neurosurgery, University of Cambridge School for Clinical Medicine, UK.
Sibson
N R
NR
Maskell
L
L
Carpenter
T A
TA
Hall
L D
LD
Pickard
J D
JD
D000704:Analysis of Variance; D000818:Animals; D002544:Cerebral Infarction / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D004058:Diffusion; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000627:therapeutic use*; D005069:Evaluation Studies as Topic; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D002546:Ischemic Attack, Transient / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate