Evidence for a neuroprotective effect of pyrid-3-yl-sulphonyl-urea in photochemically induced focal ischaemia in rats: magnetic resonance imaging evaluation.
A neuroprotective effect can be obtained with N-[(4-cycloheptylaminopyrid-3-yl)sulphonyl]N'-cycloheptyl urea (BM27), a pyrid-3-yl-sulphonylurea structurally related to torasemide, a loop diuretic. We have investigated the neuroprotective effect of BM27 by magnetic resonance imaging and use of the photothrombotic model of cerebral infarction in the rat. This method enables non-invasive quantification of the extent of the cerebral oedema from T2-weighted spin-echo images. This article reports the evolution of the extent of oedema with time (0.5, 1, 2, 4, 6, 24 and 48 h, 7 and 15 days and 1 month after induction of the lesion) in rats pretreated with 5 mg kg(-1) BM27 or an appropriate control. At all times, the rats treated with BM27 had, on average, smaller lesions than control rats (30% decrease between 2 h and 6 h). These results strongly suggest a significant (P < 0.01) but modest neuroprotective effect of BM27 in ischaemic cerebral stroke. Further investigations should be performed to determine if BM27 or its analogues are of clinical interest.
Baudelet
C
C
Laboratory of Medicinal Chemistry and Radiopharmacy, Université Catholique de Louvain, Brussels, Belgium.
Demeure
R
R
Frois
A
A
Masereel
B
B
Goudemant
J F
JF
Ritter
C
C
Gallez
B
B
D000818:Animals; D001929:Brain Edema / Q000209:etiology / Q000473:pathology*; D002544:Cerebral Infarction / Q000473:pathology*; D007511:Ischemia / Q000473:pathology*; D008027:Light / Q000009:adverse effects; D008279:Magnetic Resonance Imaging; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D013927:Thrombosis / Q000209:etiology
D018696:Neuroprotective Agents; D013453:Sulfonylurea Compounds; C104936:BM 27