Magnetic resonance imaging studies on the effect of the fibrinogen-lowering agent ancrod on cerebral lesions in two rat models of acute stroke.
In vivo magnetic resonance imaging was used to study the effect of ancrod (CAS 9046-56-4, Arwin), a plasma fibrinogen level lowering agent, on brain lesion in two rat models of acute focal cerebral ischaemia. Total lesion volume was determined by multislice T2-weighted magnetic resonance imaging 24 h after permanent middle cerebral artery occlusion. Intravenous infusion of ancrod starting 30 min after middle cerebral artery occlusion at dosages of 10, 30, 50 or 70 IU/kg (n = 9/group) significantly diminished cerebral lesion volume by 20 to 33% as compared to vehicle-infused controls (n = 12). None of the ancrod-treated rats showed evidence of intracerebral bleeding on T2-weighted magnetic resonance images taken after 24 h. In photochemically induced (rose bengal) unilateral thrombotic cortical infarction brain damage was displayed by multislice diffusion-weighted magnetic resonance imaging after 24 h. Again, post treatment with ancrod reduced total volume of cerebral lesion dose-dependently from 142 +/- 28 mm3 in the controls (n = 10) to 121 +/- 28 mm3 (n = 10) and 111 +/- 20 mm3 (n = 11, p < 0.05) in rats treated with 10 and 30 IU/kg ancrod, respectively (means +/- S.D.). These results suggest cerebroprotection in focal cerebral ischaemia by improvements in the cerebral microcirculation which may offer a potential and safe approach for therapy of acute stroke.
Elger
B
B
Knoll AG, Ludwigshafen, Germany.
Laux
V
V
Schwarz
M
M
D000208:Acute Disease; D000721:Ancrod / Q000627:therapeutic use*; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000473:pathology; D001921:Brain / Q000473:pathology*; D002536:Cerebral Arteries / Q000502:physiology; D002544:Cerebral Infarction / Q000139:chemically induced / Q000473:pathology; D002561:Cerebrovascular Disorders / Q000188:drug therapy* / Q000473:pathology*; D005340:Fibrinogen / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D010777:Photochemistry; D051381:Rats; D011918:Rats, Inbred SHR
D005343:Fibrinolytic Agents; D005340:Fibrinogen; D000721:Ancrod