Postischemic therapy with MK-801 (dizocilpine) in a primate model of transient focal brain ischemia

Roland N. Auer, Stuart G. Coupland, Gregor W. Jason, David P. Archer, Jacqueline Payne, Alan J. Belzberg, Masefumi Ohtaki, Bruce I. Tranmer

Research output: Contribution to journalArticlepeer-review


The purpose of this study was to develop a primate model for assessing EEG, behavior and histology, and to test the effect of NMDA receptor blockade in transient focal ischemia. Squirrel monkeys (Saimiri sciureus) under halothane anesthesia were subjected to 110 min of transient focal ischemia (n = 15) by temporary clip occlusion of the MCA. An eight-lead EEG was recorded. Neurobehavioral testing was done in a subgroup of animals (n = 6). Brain temperature (37.5°C) was monitored and controlled to avoid hypothermia or intergroup temperature differences, and blood pressure was regulated to 60 mmHg. The entire brain was subserially sectioned, and 52 standardized coronal sections encompassing the infarct were examined histologically 2 wk after the ischemia. Animals were randomized to receive either (+-5-methyl-10,11- dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) 1 mg/kg of maleate salt or carrier solution, 20 min and again at 12 h after the onset of ischemia. Cingulate and retrosplenial cortex were examined for NMDA- antagonist-induced neuronal necrosis. No reduction, or trend toward reduction of neurobehavioral deficit was seen with MK-801. MCA occlusion reduced EEG power over the ischemic hemisphere. MK-801 appeared to cause brain activation, and globally increased power at several frequencies. MK-801 did not reduce infarction in either neocortex (p > 0.05) or striatum (p > 0.05). No selective neuronal necrosis was seen in the cingulate or retrosplenial cortex. We conclude that MK-801 given 20 min after the onset of transient ischemia offers no significant neuroprotective effect against either neurobehavioral deficit or ischemic infarction in this model of transient focal ischemia. Further experiments in unanesthetized animals are necessary to determine if MK-801-induced necrosis exists in the gyrencephalic brain, but the enhancement of primate brain electrical activity by MK-801 suggests that brain activation occurs in primates as it does in rodents.

Original languageEnglish (US)
Pages (from-to)193-210
Number of pages18
JournalMolecular and Chemical Neuropathology
Issue number2-3
StatePublished - 1996
Externally publishedYes


  • Ischemia
  • NMDA antagonist
  • brain
  • channel blocker
  • focal
  • glutamate
  • necrosis
  • primate
  • transient

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology


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