DIFFUSION-WEIGHTED AND T2-WEIGHTED IMAGING - EVALUATION OF EDEMA REDUCTION IN FOCAL CEREBRAL-ISCHEMIA BY THE CALCIUM AND SEROTONIN ANTAGONIST LEVEMOPAMIL
J. Seega et B. Elger, DIFFUSION-WEIGHTED AND T2-WEIGHTED IMAGING - EVALUATION OF EDEMA REDUCTION IN FOCAL CEREBRAL-ISCHEMIA BY THE CALCIUM AND SEROTONIN ANTAGONIST LEVEMOPAMIL, Magnetic resonance imaging, 11(3), 1993, pp. 401-409
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.