Combination drug therapy using edaravone and Daio-Orengedoku-to after transient focal ischemia in rats.
In this study, we investigated the effect of Daio-Orengedoku-to (DOT) on ischemic brain damage in a rat model of focal ischemia-reperfusion and attempted to identify synergistic effects for the combination of edaravone and DOT against ischemic insult. Ischemia was induced by intraluminal occlusion of the right middle cerebral artery for 2 h and reperfusion followed for 22 h. To determine the neuroprotective effect of DOT, it was administered orally just before reperfusion and then 2 h after reperfusion. To examine the effects of combination therapy on survival, rats were divided into groups treated with edaravone, DOT, and edaravone and DOT. Microglial activation, neutrophil infiltration and brain-derived neurotrophic factor (BDNF) expression were examined in surviving animals. Infarct volume was significantly reduced by DOT (100, 200 and 400 mg/kg; P < 0.05), and edaravone plus DOT markedly improved the survival rate after transient ischemia (P = 0.0133). Microglial activation was reduced by edaravone and DOT and their combination (P < 0.05), and neutrophil infiltration was lowered in these groups (P < 0.05). BDNF-positive cells were increased in the combination edaravone and DOT group (P < 0.05). It appears that the neuroprotective mechanisms of combined therapy involve inhibition of microglial activation, reduction of invading neutrophils and enhancement of BDNF expression.
Cho
K-H
KH
College of Oriental Medicine, Kyung Hee University, Seoul, Korea.
Oh
J K
JK
Jang
Y S
YS
Jung
J W
JW
Oh
H R
HR
Park
E-K
EK
Kim
D H
DH
Moon
S-K
SK
Kim
D-H
DH
Ryu
J H
JH
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D004359:Drug Therapy, Combination; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000188:drug therapy*; D008297:Male; D017628:Microglia / Q000187:drug effects; D018696:Neuroprotective Agents; D020556:Neutrophil Infiltration / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000523:psychology
D019208:Brain-Derived Neurotrophic Factor; D004365:Drugs, Chinese Herbal; D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; C061676:oren gedoku to; D000077553:Edaravone; D000983:Antipyrine