Failure of mk-801 to reduce infarct volume in thrombotic middle cerebral artery occlusion in rats

Hiroshi Yao, Myron D. Ginsberg, Brant D. Watson, Ricardo Prado, W. Dalton Dietrich, Susan Kraydieh, Raul Busto

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Background and Purpose: We examined the effects of the noncompetitive N-methyl-D-aspartate receptor antagonist MK-801 using a newly developed stroke model of thrombotic distal middle cerebral artery occlusion under conditions of carefully controlled head temperature. Methods: Male Sprague-Dawley rats were treated with 1 mg/kg of MK-801 or saline before the induction of ischemia. An argon laser-activated dye laser (562 nm) was used to cause thrombotic distal middle cerebral artery occlusion. In experiments 1 and 2, the single laser beam (20 mW) was separated 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 minutes; the three points were then irradiated for 3 minutes. In experiment 3, higher power of the laser (three separate irradiations using a single beam of 20 mW) was used. The ipsilateral common carotid artery was occluded permanently, and the contralateral carotid artery was occluded for 60 minutes. Head temperature was controlled at 36°C in experiment 1 and not controlled in experiments 2 and 3. Three days after the ischemic insult, brains were perfusion-fixed and infarct volumes were determined. Results: Head temperature was mildly hypothermic (34-35°C before ischemia, with a further decrease of 1-2°C during the initial 60 minutes of ischemia) in experiment 2. However, no differences were observed in head temperature between the MK-801-treated 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 and 3, respectively. However, MK-801 also failed to reduce infarct volumes in experiments 2 and 3. Conclusions: MK-801 is not effective in this stroke model of focal thrombotic infarction under conditions of either controlled (normothermic) or uncontrolled (mildly hypothermic) head temperature.

Original languageEnglish (US)
Pages (from-to)864-870
Number of pages7
JournalStroke
Volume24
Issue number6
DOIs
StatePublished - Jun 1993

Keywords

  • Cerebral ischemia
  • Glutamates
  • MK-801
  • Photothrombosis
  • Rats

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Failure of mk-801 to reduce infarct volume in thrombotic middle cerebral artery occlusion in rats'. Together they form a unique fingerprint.

Cite this