Development and characterization of a Yucatan miniature biomedical pig permanent middle cerebral artery occlusion stroke model

Simon R. Platt, Shannon P. Holmes, Elizabeth W. Howerth, Kylee Jo J. Duberstein, C. R. Dove, Holly A. Kinder, Emily L. Wyatt, Amie V. Linville, Vivian W. Lau, Steven L. Stice, William D Hill, David C Hess, Franklin D. West

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Background: Efforts to develop stroke treatments have met with limited success despite an intense need to produce novel treatments. The failed translation of many of these therapies in clinical trials has lead to a close examination of the therapeutic development process. One of the major factors believed to be limiting effective screening of these treatments is the absence of an animal model more predictive of human responses to treatments. The pig may potentially fill this gap with a gyrencephalic brain that is larger in size with a more similar gray-white matter composition to humans than traditional stroke animal models. In this study we develop and characterize a novel pig middle cerebral artery occlusion (MCAO) ischemic stroke model.Methods: Eleven male pigs underwent MCAO surgery with the first 4 landrace pigs utilized to optimize stroke procedure and 7 additional Yucatan stroked pigs studied over a 90 day period. MRI analysis was done at 24 hrs and 90 days and included T2w, T2w FLAIR, T1w FLAIR and DWI sequences and associated ADC maps. Pigs were sacrificed at 90 days and underwent gross and microscopic histological evaluation. Significance in quantitative changes was determined by two-way analysis of variance and post-hoc Tukey's Pair-Wise comparisons.Results: MRI analysis of animals that underwent MCAO surgery at 24 hrs had hyperintense regions in T2w and DWI images with corresponding ADC maps having hypointense regions indicating cytotoxic edema consistent with an ischemic stroke. At 90 days, region of interest analysis of T1 FLAIR and ADC maps had an average lesion size of 59.17 cc, a loss of 8% brain matter. Histological examination of pig brains showed atrophy and loss of tissue, consistent with MRI, as well as glial scar formation and macrophage infiltration.Conclusions: The MCAO procedure led to significant and consistent strokes with high survivability. These results suggest that the pig model is potentially a robust system for the study of stroke pathophysiology and potential diagnostics and therapeutics.

Original languageEnglish (US)
Article number5
JournalExperimental and Translational Stroke Medicine
Volume6
Issue number1
DOIs
StatePublished - Mar 23 2014

Fingerprint

Middle Cerebral Artery Infarction
Swine
Stroke
Brain
Animal Models
Neuroglia
Atrophy
Cicatrix
Edema
Analysis of Variance
Therapeutics
Macrophages
Clinical Trials

Keywords

  • Magnetic resonance imaging
  • Pig
  • Stroke model

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Cognitive Neuroscience

Cite this

Development and characterization of a Yucatan miniature biomedical pig permanent middle cerebral artery occlusion stroke model. / Platt, Simon R.; Holmes, Shannon P.; Howerth, Elizabeth W.; Duberstein, Kylee Jo J.; Dove, C. R.; Kinder, Holly A.; Wyatt, Emily L.; Linville, Amie V.; Lau, Vivian W.; Stice, Steven L.; Hill, William D; Hess, David C; West, Franklin D.

In: Experimental and Translational Stroke Medicine, Vol. 6, No. 1, 5, 23.03.2014.

Research output: Contribution to journalArticle

Platt, SR, Holmes, SP, Howerth, EW, Duberstein, KJJ, Dove, CR, Kinder, HA, Wyatt, EL, Linville, AV, Lau, VW, Stice, SL, Hill, WD, Hess, DC & West, FD 2014, 'Development and characterization of a Yucatan miniature biomedical pig permanent middle cerebral artery occlusion stroke model', Experimental and Translational Stroke Medicine, vol. 6, no. 1, 5. https://doi.org/10.1186/2040-7378-6-5
Platt, Simon R. ; Holmes, Shannon P. ; Howerth, Elizabeth W. ; Duberstein, Kylee Jo J. ; Dove, C. R. ; Kinder, Holly A. ; Wyatt, Emily L. ; Linville, Amie V. ; Lau, Vivian W. ; Stice, Steven L. ; Hill, William D ; Hess, David C ; West, Franklin D. / Development and characterization of a Yucatan miniature biomedical pig permanent middle cerebral artery occlusion stroke model. In: Experimental and Translational Stroke Medicine. 2014 ; Vol. 6, No. 1.
@article{ab07f396992140108cb6bda1c5054fd0,
title = "Development and characterization of a Yucatan miniature biomedical pig permanent middle cerebral artery occlusion stroke model",
abstract = "Background: Efforts to develop stroke treatments have met with limited success despite an intense need to produce novel treatments. The failed translation of many of these therapies in clinical trials has lead to a close examination of the therapeutic development process. One of the major factors believed to be limiting effective screening of these treatments is the absence of an animal model more predictive of human responses to treatments. The pig may potentially fill this gap with a gyrencephalic brain that is larger in size with a more similar gray-white matter composition to humans than traditional stroke animal models. In this study we develop and characterize a novel pig middle cerebral artery occlusion (MCAO) ischemic stroke model.Methods: Eleven male pigs underwent MCAO surgery with the first 4 landrace pigs utilized to optimize stroke procedure and 7 additional Yucatan stroked pigs studied over a 90 day period. MRI analysis was done at 24 hrs and 90 days and included T2w, T2w FLAIR, T1w FLAIR and DWI sequences and associated ADC maps. Pigs were sacrificed at 90 days and underwent gross and microscopic histological evaluation. Significance in quantitative changes was determined by two-way analysis of variance and post-hoc Tukey's Pair-Wise comparisons.Results: MRI analysis of animals that underwent MCAO surgery at 24 hrs had hyperintense regions in T2w and DWI images with corresponding ADC maps having hypointense regions indicating cytotoxic edema consistent with an ischemic stroke. At 90 days, region of interest analysis of T1 FLAIR and ADC maps had an average lesion size of 59.17 cc, a loss of 8{\%} brain matter. Histological examination of pig brains showed atrophy and loss of tissue, consistent with MRI, as well as glial scar formation and macrophage infiltration.Conclusions: The MCAO procedure led to significant and consistent strokes with high survivability. These results suggest that the pig model is potentially a robust system for the study of stroke pathophysiology and potential diagnostics and therapeutics.",
keywords = "Magnetic resonance imaging, Pig, Stroke model",
author = "Platt, {Simon R.} and Holmes, {Shannon P.} and Howerth, {Elizabeth W.} and Duberstein, {Kylee Jo J.} and Dove, {C. R.} and Kinder, {Holly A.} and Wyatt, {Emily L.} and Linville, {Amie V.} and Lau, {Vivian W.} and Stice, {Steven L.} and Hill, {William D} and Hess, {David C} and West, {Franklin D.}",
year = "2014",
month = "3",
day = "23",
doi = "10.1186/2040-7378-6-5",
language = "English (US)",
volume = "6",
journal = "Experimental and Translational Stroke Medicine",
issn = "2040-7378",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Development and characterization of a Yucatan miniature biomedical pig permanent middle cerebral artery occlusion stroke model

AU - Platt, Simon R.

AU - Holmes, Shannon P.

AU - Howerth, Elizabeth W.

AU - Duberstein, Kylee Jo J.

AU - Dove, C. R.

AU - Kinder, Holly A.

AU - Wyatt, Emily L.

AU - Linville, Amie V.

AU - Lau, Vivian W.

AU - Stice, Steven L.

AU - Hill, William D

AU - Hess, David C

AU - West, Franklin D.

PY - 2014/3/23

Y1 - 2014/3/23

N2 - Background: Efforts to develop stroke treatments have met with limited success despite an intense need to produce novel treatments. The failed translation of many of these therapies in clinical trials has lead to a close examination of the therapeutic development process. One of the major factors believed to be limiting effective screening of these treatments is the absence of an animal model more predictive of human responses to treatments. The pig may potentially fill this gap with a gyrencephalic brain that is larger in size with a more similar gray-white matter composition to humans than traditional stroke animal models. In this study we develop and characterize a novel pig middle cerebral artery occlusion (MCAO) ischemic stroke model.Methods: Eleven male pigs underwent MCAO surgery with the first 4 landrace pigs utilized to optimize stroke procedure and 7 additional Yucatan stroked pigs studied over a 90 day period. MRI analysis was done at 24 hrs and 90 days and included T2w, T2w FLAIR, T1w FLAIR and DWI sequences and associated ADC maps. Pigs were sacrificed at 90 days and underwent gross and microscopic histological evaluation. Significance in quantitative changes was determined by two-way analysis of variance and post-hoc Tukey's Pair-Wise comparisons.Results: MRI analysis of animals that underwent MCAO surgery at 24 hrs had hyperintense regions in T2w and DWI images with corresponding ADC maps having hypointense regions indicating cytotoxic edema consistent with an ischemic stroke. At 90 days, region of interest analysis of T1 FLAIR and ADC maps had an average lesion size of 59.17 cc, a loss of 8% brain matter. Histological examination of pig brains showed atrophy and loss of tissue, consistent with MRI, as well as glial scar formation and macrophage infiltration.Conclusions: The MCAO procedure led to significant and consistent strokes with high survivability. These results suggest that the pig model is potentially a robust system for the study of stroke pathophysiology and potential diagnostics and therapeutics.

AB - Background: Efforts to develop stroke treatments have met with limited success despite an intense need to produce novel treatments. The failed translation of many of these therapies in clinical trials has lead to a close examination of the therapeutic development process. One of the major factors believed to be limiting effective screening of these treatments is the absence of an animal model more predictive of human responses to treatments. The pig may potentially fill this gap with a gyrencephalic brain that is larger in size with a more similar gray-white matter composition to humans than traditional stroke animal models. In this study we develop and characterize a novel pig middle cerebral artery occlusion (MCAO) ischemic stroke model.Methods: Eleven male pigs underwent MCAO surgery with the first 4 landrace pigs utilized to optimize stroke procedure and 7 additional Yucatan stroked pigs studied over a 90 day period. MRI analysis was done at 24 hrs and 90 days and included T2w, T2w FLAIR, T1w FLAIR and DWI sequences and associated ADC maps. Pigs were sacrificed at 90 days and underwent gross and microscopic histological evaluation. Significance in quantitative changes was determined by two-way analysis of variance and post-hoc Tukey's Pair-Wise comparisons.Results: MRI analysis of animals that underwent MCAO surgery at 24 hrs had hyperintense regions in T2w and DWI images with corresponding ADC maps having hypointense regions indicating cytotoxic edema consistent with an ischemic stroke. At 90 days, region of interest analysis of T1 FLAIR and ADC maps had an average lesion size of 59.17 cc, a loss of 8% brain matter. Histological examination of pig brains showed atrophy and loss of tissue, consistent with MRI, as well as glial scar formation and macrophage infiltration.Conclusions: The MCAO procedure led to significant and consistent strokes with high survivability. These results suggest that the pig model is potentially a robust system for the study of stroke pathophysiology and potential diagnostics and therapeutics.

KW - Magnetic resonance imaging

KW - Pig

KW - Stroke model

UR - http://www.scopus.com/inward/record.url?scp=84897947723&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84897947723&partnerID=8YFLogxK

U2 - 10.1186/2040-7378-6-5

DO - 10.1186/2040-7378-6-5

M3 - Article

VL - 6

JO - Experimental and Translational Stroke Medicine

JF - Experimental and Translational Stroke Medicine

SN - 2040-7378

IS - 1

M1 - 5

ER -