FAILURE OF MK-801 TO REDUCE INFARCT VOLUME IN THROMBOTIC MIDDLE CEREBRAL-ARTERY OCCLUSION IN RATS

Background and Purpose: We examined the effects of the noncompetitive N-methyl-D-aspartate receptor antagonist MK-801 using a newly develope d stroke model of thrombotic distal middle cerebral artery occlusion u nder conditions of carefully controlled head temperature. Methods. Mal e Sprague-Dawley rats were treated with 1 mg/kg of MK-801 or saline be fore the induction of ischemia. An argon laser-activated dye laser (56 2 nm) was used to cause thrombotic distal middle cerebral artery occlu sion. In experiments 1 and 2, the single laser beam (20 mW) was separa ted into three beams. Each beam was positioned onto the distal middle cerebral artery at three sites along the vessel. The photosensitizing dye rose bengal (20 mg/kg) was administered intravenously over 2 minut es; the three points were then irradiated for 3 minutes. In experiment 3, higher power of the laser (three separate irradiations using a sin gle beam of 20 mW was used. The ipsilateral common carotid artery was occluded permanently, and the contralateral carotid artery was occlude d for 60 minutes. Head temperature was controlled at 36-degrees-C in e xperiment 1 and not controlled in experiments 2 and 3. Three days afte r the ischemic insult, brains were perfusion-fixed and infarct volumes were determined. Results: Head temperature was mildly hypothermic (34 -35-degrees-C before ischemia, with a further decrease of 1-2-degrees- C during the initial 60 minutes of ischemia) in experiment 2. However, no differences were observed in head temperature between the MK-801-t reated and control groups. Cortical infarct volume in experiment 1 was 89+/-29 mm3 (mean+/-SD) in the treated group, which was not different from the control value of 84+/-40 mm3. Infarct volumes were smaller ( 58+/-35 mm3 and 54+/-14 mm3) in the control groups of experiments 2 an d 3, respectively. However, MK-801 also failed to reduce infarct volum es in experiments 2 and 3. Conclusions: MK-801 is not effective in thi s stroke model of focal thrombotic infarction under conditions of eith er controlled (normothermic) or uncontrolled (mildly hypothermic) head temperature.