Diffusion- and T2-weighted imaging: evaluation of oedema reduction in focal cerebral ischaemia 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 middle cerebral artery occlusion (MCAO) in spontaneously hypertensive rats. Areas of increased signal intensity strongly correlate with histochemically determined areas of ischaemia in corresponding brain planes (r = 0.84; p < .001). In a separate cohort of animals, spatial progression of oedema formation was studied at 3, 24, 48, and 72 hr after MCAO showing a maximum extent at 48 hr. Early events in cerebral ischaemia were 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-weighted spin-echo images 24 hr after MCAO. Combined pre- and posttreatment with isradipine showed a 21% inhibition of oedema progression. Application of a single dose (10 mg/kg) of levemopamil either 30 min before or 2 hr after MCAO revealed a diminution of oedematous areas by 19% and 25%, respectively. Levemopamil reduces the extent of ischaemic brain oedema in an established stroke model.
Research and Development, Molecular Pharmacology and Screening, Knoll AG, Ludwigshafen, Germany.
J
J
Seega
B
B
Elger
D000818:Animals; D001921:Brain / Q000473:pathology; D001929:Brain Edema / Q000175:diagnosis* / Q000209:etiology; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002546:Ischemic Attack, Transient / Q000150:complications / Q000188:drug therapy / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D014700:Verapamil / Q000031:analogs & derivatives* / Q000627:therapeutic use
D002121:Calcium Channel Blockers; D012702:Serotonin Antagonists; D014700:Verapamil; C052752:emopamil