SNX-111, a novel, presynaptic N-type calcium channel antagonist, is neuroprotective against focal cerebral ischemia in rabbits

Miguel A. Perez-Pinzon, Midori A. Yenari, Guo H. Sun, David M. Kunis, Gary K. Steinberg

Research output: Contribution to journalArticle

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Abstract

Cytosolic Ca2+ overload has been proposed as a main cause of neuronal injury during cerebral ischemia. SNX-111, a synthetic product of the naturally occurring ω-conotoxin MVIIA, is a novel, presynaptic N-type Ca2+ channel antagonist and has been reported to be neuroprotective against cerebral ischemia. We studied the neuroprotective effects of SNX-111 in a rabbit model of focal cerebral ischemia. New Zealand white male rabbits (2.5- 3.5 kg) were given 1 mg/kg/h i.v. SNX-111 (n=8) or normal saline (n=8) 10 min after onset of a 2-h period of transient focal cerebral ischemia induced by occlusion of the left middle cerebral, anterior cerebral and internal carotid arteries followed by 4 h reperfusion. SNX-111 significantly attenuated overall cortical ischemic neuronal damage by 44% (saline, 38.7±3.0%; SNX- 111, 21.5±6.0%, P<0.05) and regions of hyperintensity on T2-weighted MRI by 30% (saline, 70.6±4.0%; SNX-111, 49.3±11.0%, P<0.05). No significant difference in (regional cerebral blood flow) rCBF or MAP (mean arterial blood pressure) was found between SNX-111- and saline-treated rabbits suggesting that neuroprotection is due to a cellular effect. We conclude that SNX-111 reduces ischemic injury in this model. Its use as a clinical neuroprotective agent for cerebrovascular surgery or stroke should be investigated further.

Original languageEnglish (US)
Pages (from-to)25-31
Number of pages7
JournalJournal of the Neurological Sciences
Volume153
Issue number1
DOIs
StatePublished - Dec 9 1997
Externally publishedYes

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Keywords

  • Calcium
  • Conopeptides
  • Excitotoxicity
  • Focal cerebral ischemia
  • MVIIA
  • Rabbit
  • Stroke

ASJC Scopus subject areas

  • Aging
  • Clinical Neurology
  • Surgery
  • Developmental Neuroscience
  • Neurology
  • Neuroscience(all)

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