Effect of CP101,606, a novel NR2B subunit antagonist of the N-methyl-D- aspartate receptor, on the volume of ischemic brain damage and cytotoxic brain edema after middle cerebral artery occlusion in the feline brain

Xiao Di, Ross Bullock, Joe Watson, Panos Fatouros, Bertrand Chenard, Frost White, Frank Corwin

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

Background and Purpose: The purpose of this study was to test the hypothesis that the neuroprotective compound CP101,606 will ameliorate the increase in lactate, retard the development of cytotoxic edema, and decrease the infarct volume after ischemic stroke. Methods: Seventeen adult cats were allocated to control (n=7) and CP101,606-treated groups (n=10). Transorbital middle cerebral artery occlusion was performed under anesthesia. Extracellular fluid lactate by microdialysis as well as infarct volume measurement by triphenyltetrazolium chloride (TTC)-stained section, with and without neuroprotective agents, was used to determine the value of these potential 'surrogate markers' of ischemic damage. Results: The control group showed an increased dialysate lactate (15.5% increase) at 30 minutes and a peak (332.0% increase) in dialysate lactate at 1 hour after middle cerebral artery occlusion compared with the drug-treated group. Significant differences between control and drug-treated groups were seen in the rate of fall of the apparent diffusion coefficient at both 1 and 5 hours. A close correlation was seen between the 1- and 5-hour apparent diffusion coefficient maps and the TTC-stained sections. There was a significantly smaller lesion in the CP101,606-treated group (62.9% reduction in infarct size compared with the control group; P<.001). Conclusions: CP101,606 ranks very highly among the current neuroprotection candidates for clinical trials, and its excellent safety record in both animals and phase II studies in conscious, moderate head injury patients suggests that it will be highly effective in human occlusive stroke.

Original languageEnglish (US)
Pages (from-to)2244-2251
Number of pages8
JournalStroke
Volume28
Issue number11
DOIs
StatePublished - Nov 1997

Keywords

  • Brain edema
  • Cats
  • Glutamate antagonist

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

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