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.
College of Oriental Medicine, Kyung Hee University, Seoul, Korea.
K-H
KH
Cho
J K
JK
Oh
Y S
YS
Jang
J W
JW
Jung
H R
HR
Oh
E-K
EK
Park
D H
DH
Kim
S-K
SK
Moon
D-H
DH
Kim
J H
JH
Ryu
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