Neuroprotective effects of a novel broad-spectrum cation channel blocker, LOE 908 MS, on experimental focal ischemia: a multispectral study.
Thirty-four rats undergoing 90 minutes of temporary middle cerebral artery occlusion were randomly and blindly assigned to vehicle or (RS)-(3,4-dihydro-6, 7-dimethoxyisoquinoline-1-gamma1)-2-phenyl-N,N-di-2-(2, 3, 4-trimethoxyphenyl)ethyl acetamide (LOE 908 MS; 0.5 mg/kg) i.v. bolus at 30 minutes after arterial occlusion followed by a 5 mg/kg/hr i.v. infusion for 3.8 hours (n =17/group). Perfusion-, diffusion- and T(2)-weighted magnetic resonance imaging was performed before treatment and repeatedly after treatment. Multispectral analysis was used to define ischemic abnormalities. The size of the ischemic abnormalities, including the ischemic core and penumbra, was not different between the two groups before treatment. However, a significant difference in ischemic lesion size was detected beginning 1.5 hours after treatment. The size of the ischemic core was significantly smaller in the treatment group, while the size of the ischemic penumbra was similar in the two groups at 85 minutes after arterial occlusion. Postmortem infarct size at 24 hours was significantly smaller in the drug-treated group than in the placebo group. These results demonstrate that LOE 908 MS can reduce ischemic lesion size, which is probably attributable to inhibition of expansion of the ischemic core. J. Magn. Reson. Imaging 1999;10:138-145.
Li
F
F
Department of Neurology, UMass Memorial Health Care and University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA. fhli@wpi.edu
Carano
R A
RA
Irie
K
K
Tatlisumak
T
T
Silva
M D
MD
Pschorni
U
U
Sotak
C H
CH
Fisher
M
M
D000081:Acetamides / Q000627:therapeutic use*; D000818:Animals; D001921:Brain / Q000473:pathology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D007473:Ion Channels / Q000187:drug effects*; D002546:Ischemic Attack, Transient / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D007546:Isoquinolines / Q000627:therapeutic use*; D016018:Least-Squares Analysis; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods / Q000706:statistics & numerical data; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D013997:Time Factors
D000081:Acetamides; D007473:Ion Channels; D007546:Isoquinolines; D018696:Neuroprotective Agents; C081356:LOE 908