Multimodal assessment of neuroprotection applied to the use of MK-801 in the endothelin-1 model of transient focal brain ischemia

Slavianka Georgieva Moyanova, Lidia Vasileva Kortenska, Rumiana Gesheva Mitreva, Vyara Dincova Pashova, Richard Teke Ngomba, Ferdinando Nicoletti

Research output: Contribution to journalArticle

Abstract

Transient focal ischemia produced by local infusion of endothelin-1 (ET1) in the territory of the middle cerebral artery has been proposed as a potentially useful model for the screening of drugs developed for the treatment of thrombo-embolic stroke. However, most of the data rely exclusively on the assessment of the infarct volume, which is only a partial predictor of the neurological outcome of stroke. Here, we have validated the model using a multimodal approach for the assessment of neuroprotection, which includes (i) determination of the infarct volume by 2,3,5-triphenyltetrazolium chloride staining; (ii) an in-depth behavioral analysis of the neurological deficit; and (iii) an EEG analysis of electrophysiological abnormalities in the peri-infarct somatosensory forelimb cortical area, S1FL. The non-competitive NMDA receptor antagonist, MK-801 (3 mg/kg, injected i.p. 20 min after ET1 infusion in conscious rats) could reduce the infarct volume, reverse the EEG changes occurring at early times post-ET1, and markedly improve the neurological deficit in ischemic animals. The latter effect, however, was visible at day 3 post-ET1, because the drug itself produced substantial behavioral abnormalities at earlier times. We conclude that a multimodal approach can be applied to the ET1 model of focal ischemia, and that MK-801 can be used as a reference compound to which the activity of safer neuroprotective drugs should be compared.

Original languageEnglish
Pages (from-to)58-67
Number of pages10
JournalBrain Research
Volume1153
Issue number1
DOIs
Publication statusPublished - Jun 11 2007

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Keywords

  • Electrophysiological outcome
  • Endothelin-1 model of ischemia
  • MK-801
  • Neurological deficit
  • Neuroprotection

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)

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