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.