A new model of cortical stroke in the rhesus macaque

G. Alexander West, Kiarash J. Golshani, Kristian Doyle, Nikola S. Lessov, Theodore R. Hobbs, Steven G. Kohama, Martin M. Pike, Christopher D. Kroenke, Marjorie R. Grafe, Maxwell D. Spector, Eric T. Tobar, Roger P. Simon, Mary P. Stenzel-Poore

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Primate models are essential tools for translational research in stroke but are reportedly inconsistent in their ability to produce cortical infarcts of reproducible size. Here, we report a new stroke model using a transorbital, reversible, two-vessel occlusion approach in male rhesus macaques that produces consistent and reproducible cortical infarcts. The right middle cerebral artery (distal to the orbitofrontal branch) and both anterior cerebral arteries were occluded with vascular clips. Bilateral occlusion of the anterior cerebral artery was critical for reducing collateral flow to the ipsilateral cortex. Reversible ischemia was induced for 45, 60, or 90 mins (n2/timepoint) and infarct volume and neurologic outcome were evaluated. The infarcts were located predominantly in the cortex and increased in size with extended duration of ischemia determined by T 2 -weighted magnetic resonance imaging. Infarct volume measured by 2,3,5-triphenyl tetrazolium chloride and cresyl violet staining corroborated magnetic resonance imaging results. Neurologic deficit scores worsened gradually with longer occlusion times. A subset of animals (n5) underwent 60 mins of ischemia resulting in consistent infarct volumes primarily located to the cortex that correlated well with neurologic deficit scores. This approach offers promise for evaluating therapeutic interventions in stroke.

Original languageEnglish (US)
Pages (from-to)1175-1186
Number of pages12
JournalJournal of Cerebral Blood Flow and Metabolism
Volume29
Issue number6
DOIs
StatePublished - Jun 2009
Externally publishedYes

Fingerprint

Macaca mulatta
Anterior Cerebral Artery
Ischemia
Stroke
Neurologic Manifestations
Magnetic Resonance Imaging
Translational Medical Research
Middle Cerebral Artery
Surgical Instruments
Primates
Nervous System
Blood Vessels
Chlorides
Staining and Labeling
Therapeutics

Keywords

  • Cerebral ischemia
  • MRI
  • Neurologic deficit
  • Nonhuman primate
  • Rhesus macaque
  • Stroke

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Neurology

Cite this

West, G. A., Golshani, K. J., Doyle, K., Lessov, N. S., Hobbs, T. R., Kohama, S. G., ... Stenzel-Poore, M. P. (2009). A new model of cortical stroke in the rhesus macaque. Journal of Cerebral Blood Flow and Metabolism, 29(6), 1175-1186. https://doi.org/10.1038/jcbfm.2009.43

A new model of cortical stroke in the rhesus macaque. / West, G. Alexander; Golshani, Kiarash J.; Doyle, Kristian; Lessov, Nikola S.; Hobbs, Theodore R.; Kohama, Steven G.; Pike, Martin M.; Kroenke, Christopher D.; Grafe, Marjorie R.; Spector, Maxwell D.; Tobar, Eric T.; Simon, Roger P.; Stenzel-Poore, Mary P.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 29, No. 6, 06.2009, p. 1175-1186.

Research output: Contribution to journalArticle

West, GA, Golshani, KJ, Doyle, K, Lessov, NS, Hobbs, TR, Kohama, SG, Pike, MM, Kroenke, CD, Grafe, MR, Spector, MD, Tobar, ET, Simon, RP & Stenzel-Poore, MP 2009, 'A new model of cortical stroke in the rhesus macaque', Journal of Cerebral Blood Flow and Metabolism, vol. 29, no. 6, pp. 1175-1186. https://doi.org/10.1038/jcbfm.2009.43
West, G. Alexander ; Golshani, Kiarash J. ; Doyle, Kristian ; Lessov, Nikola S. ; Hobbs, Theodore R. ; Kohama, Steven G. ; Pike, Martin M. ; Kroenke, Christopher D. ; Grafe, Marjorie R. ; Spector, Maxwell D. ; Tobar, Eric T. ; Simon, Roger P. ; Stenzel-Poore, Mary P. / A new model of cortical stroke in the rhesus macaque. In: Journal of Cerebral Blood Flow and Metabolism. 2009 ; Vol. 29, No. 6. pp. 1175-1186.
@article{13b03ed97e7d4ca79e1de7fdc035fbd0,
title = "A new model of cortical stroke in the rhesus macaque",
abstract = "Primate models are essential tools for translational research in stroke but are reportedly inconsistent in their ability to produce cortical infarcts of reproducible size. Here, we report a new stroke model using a transorbital, reversible, two-vessel occlusion approach in male rhesus macaques that produces consistent and reproducible cortical infarcts. The right middle cerebral artery (distal to the orbitofrontal branch) and both anterior cerebral arteries were occluded with vascular clips. Bilateral occlusion of the anterior cerebral artery was critical for reducing collateral flow to the ipsilateral cortex. Reversible ischemia was induced for 45, 60, or 90 mins (n2/timepoint) and infarct volume and neurologic outcome were evaluated. The infarcts were located predominantly in the cortex and increased in size with extended duration of ischemia determined by T 2 -weighted magnetic resonance imaging. Infarct volume measured by 2,3,5-triphenyl tetrazolium chloride and cresyl violet staining corroborated magnetic resonance imaging results. Neurologic deficit scores worsened gradually with longer occlusion times. A subset of animals (n5) underwent 60 mins of ischemia resulting in consistent infarct volumes primarily located to the cortex that correlated well with neurologic deficit scores. This approach offers promise for evaluating therapeutic interventions in stroke.",
keywords = "Cerebral ischemia, MRI, Neurologic deficit, Nonhuman primate, Rhesus macaque, Stroke",
author = "West, {G. Alexander} and Golshani, {Kiarash J.} and Kristian Doyle and Lessov, {Nikola S.} and Hobbs, {Theodore R.} and Kohama, {Steven G.} and Pike, {Martin M.} and Kroenke, {Christopher D.} and Grafe, {Marjorie R.} and Spector, {Maxwell D.} and Tobar, {Eric T.} and Simon, {Roger P.} and Stenzel-Poore, {Mary P.}",
year = "2009",
month = "6",
doi = "10.1038/jcbfm.2009.43",
language = "English (US)",
volume = "29",
pages = "1175--1186",
journal = "Journal of Cerebral Blood Flow and Metabolism",
issn = "0271-678X",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - A new model of cortical stroke in the rhesus macaque

AU - West, G. Alexander

AU - Golshani, Kiarash J.

AU - Doyle, Kristian

AU - Lessov, Nikola S.

AU - Hobbs, Theodore R.

AU - Kohama, Steven G.

AU - Pike, Martin M.

AU - Kroenke, Christopher D.

AU - Grafe, Marjorie R.

AU - Spector, Maxwell D.

AU - Tobar, Eric T.

AU - Simon, Roger P.

AU - Stenzel-Poore, Mary P.

PY - 2009/6

Y1 - 2009/6

N2 - Primate models are essential tools for translational research in stroke but are reportedly inconsistent in their ability to produce cortical infarcts of reproducible size. Here, we report a new stroke model using a transorbital, reversible, two-vessel occlusion approach in male rhesus macaques that produces consistent and reproducible cortical infarcts. The right middle cerebral artery (distal to the orbitofrontal branch) and both anterior cerebral arteries were occluded with vascular clips. Bilateral occlusion of the anterior cerebral artery was critical for reducing collateral flow to the ipsilateral cortex. Reversible ischemia was induced for 45, 60, or 90 mins (n2/timepoint) and infarct volume and neurologic outcome were evaluated. The infarcts were located predominantly in the cortex and increased in size with extended duration of ischemia determined by T 2 -weighted magnetic resonance imaging. Infarct volume measured by 2,3,5-triphenyl tetrazolium chloride and cresyl violet staining corroborated magnetic resonance imaging results. Neurologic deficit scores worsened gradually with longer occlusion times. A subset of animals (n5) underwent 60 mins of ischemia resulting in consistent infarct volumes primarily located to the cortex that correlated well with neurologic deficit scores. This approach offers promise for evaluating therapeutic interventions in stroke.

AB - Primate models are essential tools for translational research in stroke but are reportedly inconsistent in their ability to produce cortical infarcts of reproducible size. Here, we report a new stroke model using a transorbital, reversible, two-vessel occlusion approach in male rhesus macaques that produces consistent and reproducible cortical infarcts. The right middle cerebral artery (distal to the orbitofrontal branch) and both anterior cerebral arteries were occluded with vascular clips. Bilateral occlusion of the anterior cerebral artery was critical for reducing collateral flow to the ipsilateral cortex. Reversible ischemia was induced for 45, 60, or 90 mins (n2/timepoint) and infarct volume and neurologic outcome were evaluated. The infarcts were located predominantly in the cortex and increased in size with extended duration of ischemia determined by T 2 -weighted magnetic resonance imaging. Infarct volume measured by 2,3,5-triphenyl tetrazolium chloride and cresyl violet staining corroborated magnetic resonance imaging results. Neurologic deficit scores worsened gradually with longer occlusion times. A subset of animals (n5) underwent 60 mins of ischemia resulting in consistent infarct volumes primarily located to the cortex that correlated well with neurologic deficit scores. This approach offers promise for evaluating therapeutic interventions in stroke.

KW - Cerebral ischemia

KW - MRI

KW - Neurologic deficit

KW - Nonhuman primate

KW - Rhesus macaque

KW - Stroke

UR - http://www.scopus.com/inward/record.url?scp=67349087972&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67349087972&partnerID=8YFLogxK

U2 - 10.1038/jcbfm.2009.43

DO - 10.1038/jcbfm.2009.43

M3 - Article

C2 - 19384334

AN - SCOPUS:67349087972

VL - 29

SP - 1175

EP - 1186

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

IS - 6

ER -