PHARMACOLOGICAL REVERSAL OF ACUTE CHANGES IN DIFFUSION-WEIGHTED MAGNETIC-RESONANCE-IMAGING IN FOCAL CEREBRAL-ISCHEMIA

Recently, diffusion-weighted magnetic resonance imaging (DWI) has been shown to visualize acute ischemic lesions in the brain before changes are observable with conventional magnetic resonance imaging. However, the underlying mechanisms of these acute DWI changes are unclear and may include both reversible and irreversible damage. In this study, we demonstrate that acute DWI lesions may be reversed with MK801 therapy postischemia. Sprague-Dawley rats (n = 12) were subjected to middle c erebral artery occlusion and DWI scans were obtained beginning 600 min postocclusion. Distinct regions of hyperintensity were observed in th e basal ganglia and cortex, corresponding with the expected distributi on of ischemia in this model. After the first scan, animals were treat ed with MK801 (0.5 mg/kg i.v.) or normal saline and subsequently scann ed again 30 and 60 min after treatment. In the control group, the area of hyperintense lesions continued to increase, by 55% in the cortex a nd 57% in the basal ganglia. MK801 therapy significantly (p < 0.01) re duced the area of damage by the third DWI scan at 60 min posttreatment (-50% cortex, -22% basal ganglia, -41% total hemisphere) compared to pretreatment scans. Tetrazolium (TTC) stains at 24 h confirmed that MK 801 significantly reduced the volumes of infarction (p < 0.05). These results demonstrate that significant portions of the acute ischemic le sion on DWI are reversible with pharmacologic intervention. .