Combined argatroban and edaravone caused additive neuroprotection against 15 min of forebrain ischemia in gerbils.
We investigated whether or not a combination of the selective thrombin inhibitor, argatroban, and the free radical scavenger, edaravone (MCI-186), ameliorates postischemic hypoperfusion and decreases mortality after 15 min of forebrain ischemia in the gerbil. Argatroban or edaravone alone significantly increased postischemic cerebral blood flow and attenuated brain edema after reperfusion. However, only the combination increased the survival ratio (P<0.05 by Mantel-Cox) and protected the damage of neuronal cells. The present study indicates that anticoagulants and free radical scavengers reciprocally function to inhibit the progression of ischemic cell damage and that a combination of these types of drugs will help to improve the outcomes after cerebral ischemia.
Jin
Yong-Jian
YJ
Department of Neurosurgery, Kochi Medical School, Okohcho, Nankoku City, Kochi, Japan.
Mima
Tatsuo
T
Raicu
Valerica
V
Park
Kae Chang
KC
Shimizu
Keiji
K
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D000983:Antipyrine / Q000031:analogs & derivatives / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives; D001834:Body Water / Q000187:drug effects / Q000378:metabolism; D001929:Brain Edema / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002544:Cerebral Infarction / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D004347:Drug Interactions / Q000502:physiology; D004359:Drug Therapy, Combination; D000077553:Edaravone; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism; D005849:Gerbillinae; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010875:Pipecolic Acids / Q000494:pharmacology*; D016548:Prosencephalon / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D013449:Sulfonamides
D000925:Anticoagulants; D016166:Free Radical Scavengers; D005609:Free Radicals; D018696:Neuroprotective Agents; D010875:Pipecolic Acids; D013449:Sulfonamides; D001120:Arginine; C031942:argatroban; D000077553:Edaravone; D000983:Antipyrine