Mild hypothermia enhances efficacy of neuroprotective agents in cerebral ischemia in rats

摘要

Immunosuppressant, FK506, a selective thrombin inhibitor, argatroban and a free radical scavenger, edaravone has been reported to reduce ischemic cortical damage after transient middle cerebral artery occlusion (MCAO) in rats. Hypothermic treatment has also been used as one of the strategies for reducing ischemic brain injury. Therefore, the aim of the present study is to determine whether mild hypothermia enhances efficacy of these neuroprotective agents (FK506, argatroban and edaravone) following transient focal ischemia in rats. Sprague-Dawley rats were subjected to MCAO using an intraluminal suture technique for 2 h. The rats were reperfused for 24 h and decapitated for infarct and edema analysis. Animals were randomly divided into the following four groups: (I) vehicle-treated, normothermic group; (II) vehicle-treated, mild hypothermic (35degC) group; (III) neuroprotective agent-treated, normothermic group; and (IV) neuroprotective agent-treated, mild hypothermic (35degC) group. The combination of neuroprotective agent and mild hypothermia (35degC) significantly reduced infarct volumes and edema volumes, while mild hypothermia or neuroprotective agent alone failed to decrease ischemic brain damage. Since all agents (FK506, argatroban and edaravone) used in this study for neuroprotection, are used clinically in human, this combined therapy may be a new therapeutic strategy for the treatment of acute stroke.