Mild hypothermia enhances the neuroprotective effects of a selective thrombin inhibitor following transient focal ischemia in rats.
The aim of this study is to determine whether a selective thrombin inhibitor, Argatroban, would prevent neuronal cell death and whether extra-mild hypothermia (35 degrees C) would enhance the neuroprotective effect of a selective thrombin inhibitor following transient focal ischemia in rats. Sprague-Dawley rats were subjected to MCAo using an intraluminal suture technique for 2 hrs. The rats were reperfused for 24 h and decapitated for infarct and edema analysis. Argatroban-treated animals received a continuous injection of argatroban (3.0 mg/kg) for 24 hrs after onset of ischemia, while vehicle-treated groups received same dose of vehicle. During ischemia, temporal muscle and rectal temperatures were monitored and maintained at 37 degrees C in the normothermic animals and at 35 degrees C in the hypothermic animals. Argatroban ameliorated the cortical ischemic damage significantly (p < 0.05). Moreover, argatroban with mild hypothermia decreased the cortical infarct or edema volume significantly compared with those of groups I and III (p < 0.05). Argatroban improved neurological symptoms significantly and also improved survival rate. These results demonstrate that extra-mild hypothermia (35 degrees C) enhances neuroprotective effects of a selective thrombin inhibitor, argatroban, suggesting that this combined therapy may be a new therapeutic strategy for the treatment of acute stroke.
Kamiya
T
T
Second Department of Internal Medicine, Nippon Medical School, Tokyo, Japan. kamiya@nms.ac.jp
Nito
C
C
Ueda
M
M
Kato
K
K
Amemiya
S
S
Terashi
A
A
Katayama
Y
Y
D000818:Animals; D000991:Antithrombins / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives; D001929:Brain Edema / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology; D002544:Cerebral Infarction / Q000473:pathology; D007036:Hypothermia, Induced; D002546:Ischemic Attack, Transient / Q000473:pathology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010875:Pipecolic Acids / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides
D000991:Antithrombins; D018696:Neuroprotective Agents; D010875:Pipecolic Acids; D013449:Sulfonamides; D001120:Arginine; C031942:argatroban