DIFFUSION-WEIGHTED AND T2-WEIGHTED IMAGING - EVALUATION OF EDEMA REDUCTION IN FOCAL CEREBRAL-ISCHEMIA BY THE CALCIUM AND SEROTONIN ANTAGONIST LEVEMOPAMIL

Magnetic resonance imaging (MRI) was used to evaluate beneficial drug effects in a rat model of focal cerebral ischaemia. Extent of cerebral oedema was measured on T2-weighted images 24 hr after permanent middl e cerebral artery occlusion (MCAO) in spontaneously hypertensive rats. Areas of increased signal intensity strongly correlate with histochem ically determined areas of ischaemia in corresponding brain planes (r = 0.84; p < .001). In a separate cohort of animals, spatial progressio n of oedema formation was studied at 3, 24, 48, and 72 hr after MCAO s howing a maximum extent at 48 hr. Early events in cerebral ischaemia w ere monitored using diffusion-weighted imaging. Effects of levemopamil [formerly (S)-emopamil], a calcium and serotonin antagonist, and the reference compound isradipine were quantified on high resolution T2-we ighted spin-echo images 24 hr after MCAO. Combined pre- and posttreatm ent with isradipine showed a 21% inhibition of oedema progression. App lication of a single dose (10 mg/kg) of levemopamil either 30 min befo re or 2 hr after MCAO revealed a diminution of oedematous areas by 19% and 25%, respectively. Levemopamil reduces the extent of ischaemic br ain oedema in an established stroke model.