Protective effects of a novel calcium antagonist with platelet-activating factor-antagonistic action, F-0401, against ischemic brain damage.
The protective effects of a novel dihydropyridine calcium antagonist with platelet-activating factor-antagonistic action, F-0401, on ischemic brain damage were investigated using experimental ischemia models in rats and gerbils. F-0401 (1 and 10 mg/kg, i.p.) prevented increases in water content, determined by the wet-dry method, in ischemic areas 24 hr after 1 hr of middle cerebral artery occlusion in the rat. Pretreatment with F-0401 (1 and 10 mg/kg, i.p.) prevented extravasation of Evans blue dye in the brain following 2 hr of bilateral carotid artery occlusion and 2 hr of reperfusion in the rat. Pretreatment with F-0401 (1 and 10 mg/kg, i.p.) protected against neuronal damage to hippocampal CA1 pyramidal cells following 3 and 5 min of forebrain ischemia in the gerbil. Immunostaining against microtubule-associated protein-2 also demonstrated preservation of CA1 neurons in F-0401-treated animals. Thus, this study shows that F-0401 prevents the occurrence of brain edema, disruption of blood-brain barrier and neuronal damage caused by cerebral ischemia. The results demonstrate that F-0401 may be a powerful candidate as a therapeutic agent in the treatment of acute stroke in man.
Chen
T
T
Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
Kato
H
H
Ban
H
H
Nakata
N
N
Liu
X H
XH
Itoyama
Y
Y
Kogure
K
K
D000818:Animals; D002545:Brain Ischemia / Q000517:prevention & control*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004095:Dihydropyridines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005070:Evans Blue / Q000378:metabolism; D005119:Extravasation of Diagnostic and Therapeutic Materials; D005849:Gerbillinae; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D007274:Injections, Intraperitoneal; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016548:Prosencephalon / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D008869:Microtubule-Associated Proteins; D010975:Platelet Aggregation Inhibitors; C082341:F 0401; D005070:Evans Blue