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

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

Research output: Contribution to journalArticle

54 Citations (Scopus)

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

Fingerprint

N-Type Calcium Channels
Calcium Channel Blockers
Brain Ischemia
Rabbits
Neuroprotective Agents
Cerebrovascular Circulation
Arterial Pressure
Conotoxins
ziconotide
Transient Ischemic Attack
Regional Blood Flow
Wounds and Injuries
Internal Carotid Artery
Reperfusion
Stroke

Keywords

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

ASJC Scopus subject areas

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

Cite this

SNX-111, a novel, presynaptic N-type calcium channel antagonist, is neuroprotective against focal cerebral ischemia in rabbits. / Perez-Pinzon, Miguel; Yenari, Midori A.; Sun, Guo H.; Kunis, David M.; Steinberg, Gary K.

In: Journal of the Neurological Sciences, Vol. 153, No. 1, 09.12.1997, p. 25-31.

Research output: Contribution to journalArticle

@article{474f1fd7971348549cee7f2872b1abde,
title = "SNX-111, a novel, presynaptic N-type calcium channel antagonist, is neuroprotective against focal cerebral ischemia in rabbits",
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.",
keywords = "Calcium, Conopeptides, Excitotoxicity, Focal cerebral ischemia, MVIIA, Rabbit, Stroke",
author = "Miguel Perez-Pinzon and Yenari, {Midori A.} and Sun, {Guo H.} and Kunis, {David M.} and Steinberg, {Gary K.}",
year = "1997",
month = "12",
day = "9",
doi = "10.1016/S0022-510X(97)00196-2",
language = "English",
volume = "153",
pages = "25--31",
journal = "Journal of the Neurological Sciences",
issn = "0022-510X",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - SNX-111, a novel, presynaptic N-type calcium channel antagonist, is neuroprotective against focal cerebral ischemia in rabbits

AU - Perez-Pinzon, Miguel

AU - Yenari, Midori A.

AU - Sun, Guo H.

AU - Kunis, David M.

AU - Steinberg, Gary K.

PY - 1997/12/9

Y1 - 1997/12/9

N2 - 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.

AB - 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.

KW - Calcium

KW - Conopeptides

KW - Excitotoxicity

KW - Focal cerebral ischemia

KW - MVIIA

KW - Rabbit

KW - Stroke

UR - http://www.scopus.com/inward/record.url?scp=0031460496&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031460496&partnerID=8YFLogxK

U2 - 10.1016/S0022-510X(97)00196-2

DO - 10.1016/S0022-510X(97)00196-2

M3 - Article

C2 - 9455974

AN - SCOPUS:0031460496

VL - 153

SP - 25

EP - 31

JO - Journal of the Neurological Sciences

JF - Journal of the Neurological Sciences

SN - 0022-510X

IS - 1

ER -