The Effect of U-74389G and MK-801 on the Size of Brain Infarction in the Transient Focal Ischemia-Reperfusion Rat Model

Kim, Jae Il; Kim, Jong Min; Yong, Dae Woong; Lee, Geun Ho; Yoon, Byung Woo; Roh, Jae Kyu; Lee, Sang Bok

Abstract

BACKGROUND: There has been considerable progression in laboratory investigations of novel therapeutic approaches aimed at protecting the brain parenchyma in the setting of the acute ischemia. The zone of ischemia surrounding an area of infarction provides a target for neuroprotective agents. MK-801 is a well known non-competitive NMDA receptor antagonist and has a neuroprotective effect to ischemic penumbra zone. U-74389G is a compound of Lazaroid(21-Aminosteroid) and a free radical scavenger which has been investigated to a neuroprotective effect to ischemic penumbra zone.
METHODS
The protective effects of single or combined pretreatment of U-74389G and MK-801 on the focal cerebral ischemia in the Sprague-Dawley rats were evaluated. The size of infarction after 2 hours occlusion-4 hours reperfusion of the left middle cerebral artery with modified Longa method was measured. The rats were given 3mg/Kg I.v. of MK-801 and U-74389G or 0.5ml of normal saline 30 minutes before middle cerebral artery occlusion. The size of infarction was described as the volume.
RESULTS
U-74389G, MK-801, and combined U-74389G and MK-801 pretreatment reduced significantly the volume of infarction 55%, 64%, 24%, respectively compared with saline pretreatment (p<0.05) and the combined U-74389G and MK-801 pretreatment reduced significantly the volume of infarcted area compared with MK-801 or U-74389G pretreatment, 44%, 37%, respectively(p<0.05). There was no significant change of infarction volume between U-74389G and MK-801 pretreatment(p>0.05).
CONCLUSIONS
These results show that single or combined pretreatment of U-74389G and MK-801 before 30 minutes of occlusion significantly reduced the volume of infarction compared with the control group in the focal cerebral occlusion-reperfusion of rats. And the combined pretreatment of U-74389G and MK-801 before 30 minutes of occlusion significantly reduced the volume of infarction compared with the single pretreatment of MK-801 or U-74389G in the focal cerebral occlusion- reperfusion of rats.