A large animal model for focal stroke: Photothrombotic lesion in the cortex of Danish Landrace pigs

Viktor Hartmann Kuang; Christian Stald Skoven; Simon Arvin; Lise Moberg Fitting; Kim Ryun Drasbek; Brian Hansen; Dariusz Orlowski; Jens Christian Hedemann Sørensen

doi:10.1016/j.jneumeth.2025.110408

A large animal model for focal stroke: Photothrombotic lesion in the cortex of Danish Landrace pigs

Viktor Hartmann Kuang, Christian Stald Skoven, Simon Arvin, Lise Moberg Fitting, Kim Ryun Drasbek, Brian Hansen, Dariusz Orlowski, Jens Christian Hedemann Sørensen

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Abstract

Background: Preclinical rodent models have been crucial for studying stroke pathophysiology. However, the limited success of translating these ischemic stroke models to human trials highlights their shortcomings. To address this, we developed a large animal porcine stroke model using Rose Bengal (RB) for photothrombotic ischemic lesioning. New method: Four Danish Landrace pigs (4–6 months old, 36–40 kg) were used in this proof-of-concept study. RB (20 mg/kg) was infused via a central venous catheter, and lesion sites in the motor and visual cortices were targeted using MRI, a stereotactic frame, and fiducial markers. Surgical access was achieved through burr holes, followed by green light exposure through the dura onto the neocortex for 30 mins. After recovery, the pigs underwent motor behavior assessment, euthanasia, and histological and MRI analyses. Results: Post-stroke, significant motor deficits were observed. Three pigs were hemiparetic and immobile, while one showed reduced exploratory behavior (42 % post-stroke vs. 81 % pre-stroke) and peripheral sniffing (∼0 % vs. 9 %). Histological analysis revealed ischemic changes, including nuclear shrinkage, pyknosis, and infarct zones with blood clots. Lesion size ranged from 1 mm² to 18 mm². Ex vivo diffusion MRI showed increased mean kurtosis in three pigs, confirming microstructural changes. Comparison with existing methods and conclusions: The model produced behavioral and histological characteristics in pigs, which have gyrencephalic brains, large intracranial vessel diameters, and a high white-to-gray matter ratio, similar to those observed in other animals and traditional models. This model can produce a reproducible isolated cortical lesion using stereotactic coordinates and/or 3D imaging.

Original language	English
Article number	110408
Journal	Journal of Neuroscience Methods
Volume	418
Number of pages	6
ISSN	0165-0270
DOIs	https://doi.org/10.1016/j.jneumeth.2025.110408
Publication status	Published - Jun 2025

Keywords

Photothrombosis
Porcine
RoseBengal
Stroke

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10.1016/j.jneumeth.2025.110408

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title = "A large animal model for focal stroke: Photothrombotic lesion in the cortex of Danish Landrace pigs",

abstract = "Background: Preclinical rodent models have been crucial for studying stroke pathophysiology. However, the limited success of translating these ischemic stroke models to human trials highlights their shortcomings. To address this, we developed a large animal porcine stroke model using Rose Bengal (RB) for photothrombotic ischemic lesioning. New method: Four Danish Landrace pigs (4–6 months old, 36–40 kg) were used in this proof-of-concept study. RB (20 mg/kg) was infused via a central venous catheter, and lesion sites in the motor and visual cortices were targeted using MRI, a stereotactic frame, and fiducial markers. Surgical access was achieved through burr holes, followed by green light exposure through the dura onto the neocortex for 30 mins. After recovery, the pigs underwent motor behavior assessment, euthanasia, and histological and MRI analyses. Results: Post-stroke, significant motor deficits were observed. Three pigs were hemiparetic and immobile, while one showed reduced exploratory behavior (42 % post-stroke vs. 81 % pre-stroke) and peripheral sniffing (∼0 % vs. 9 %). Histological analysis revealed ischemic changes, including nuclear shrinkage, pyknosis, and infarct zones with blood clots. Lesion size ranged from 1 mm² to 18 mm². Ex vivo diffusion MRI showed increased mean kurtosis in three pigs, confirming microstructural changes. Comparison with existing methods and conclusions: The model produced behavioral and histological characteristics in pigs, which have gyrencephalic brains, large intracranial vessel diameters, and a high white-to-gray matter ratio, similar to those observed in other animals and traditional models. This model can produce a reproducible isolated cortical lesion using stereotactic coordinates and/or 3D imaging.",

keywords = "Photothrombosis, Porcine, RoseBengal, Stroke",

author = "Kuang, {Viktor Hartmann} and {Stald Skoven}, Christian and Simon Arvin and {Moberg Fitting}, Lise and Drasbek, {Kim Ryun} and Brian Hansen and Dariusz Orlowski and S{\o}rensen, {Jens Christian Hedemann}",

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doi = "10.1016/j.jneumeth.2025.110408",

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A large animal model for focal stroke: Photothrombotic lesion in the cortex of Danish Landrace pigs. / Kuang, Viktor Hartmann; Stald Skoven, Christian ; Arvin, Simon et al.
In: Journal of Neuroscience Methods, Vol. 418, 110408, 06.2025.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - A large animal model for focal stroke

T2 - Photothrombotic lesion in the cortex of Danish Landrace pigs

AU - Kuang, Viktor Hartmann

AU - Stald Skoven, Christian

AU - Arvin, Simon

AU - Moberg Fitting, Lise

AU - Drasbek, Kim Ryun

AU - Hansen, Brian

AU - Orlowski, Dariusz

AU - Sørensen, Jens Christian Hedemann

PY - 2025/6

Y1 - 2025/6

N2 - Background: Preclinical rodent models have been crucial for studying stroke pathophysiology. However, the limited success of translating these ischemic stroke models to human trials highlights their shortcomings. To address this, we developed a large animal porcine stroke model using Rose Bengal (RB) for photothrombotic ischemic lesioning. New method: Four Danish Landrace pigs (4–6 months old, 36–40 kg) were used in this proof-of-concept study. RB (20 mg/kg) was infused via a central venous catheter, and lesion sites in the motor and visual cortices were targeted using MRI, a stereotactic frame, and fiducial markers. Surgical access was achieved through burr holes, followed by green light exposure through the dura onto the neocortex for 30 mins. After recovery, the pigs underwent motor behavior assessment, euthanasia, and histological and MRI analyses. Results: Post-stroke, significant motor deficits were observed. Three pigs were hemiparetic and immobile, while one showed reduced exploratory behavior (42 % post-stroke vs. 81 % pre-stroke) and peripheral sniffing (∼0 % vs. 9 %). Histological analysis revealed ischemic changes, including nuclear shrinkage, pyknosis, and infarct zones with blood clots. Lesion size ranged from 1 mm² to 18 mm². Ex vivo diffusion MRI showed increased mean kurtosis in three pigs, confirming microstructural changes. Comparison with existing methods and conclusions: The model produced behavioral and histological characteristics in pigs, which have gyrencephalic brains, large intracranial vessel diameters, and a high white-to-gray matter ratio, similar to those observed in other animals and traditional models. This model can produce a reproducible isolated cortical lesion using stereotactic coordinates and/or 3D imaging.

AB - Background: Preclinical rodent models have been crucial for studying stroke pathophysiology. However, the limited success of translating these ischemic stroke models to human trials highlights their shortcomings. To address this, we developed a large animal porcine stroke model using Rose Bengal (RB) for photothrombotic ischemic lesioning. New method: Four Danish Landrace pigs (4–6 months old, 36–40 kg) were used in this proof-of-concept study. RB (20 mg/kg) was infused via a central venous catheter, and lesion sites in the motor and visual cortices were targeted using MRI, a stereotactic frame, and fiducial markers. Surgical access was achieved through burr holes, followed by green light exposure through the dura onto the neocortex for 30 mins. After recovery, the pigs underwent motor behavior assessment, euthanasia, and histological and MRI analyses. Results: Post-stroke, significant motor deficits were observed. Three pigs were hemiparetic and immobile, while one showed reduced exploratory behavior (42 % post-stroke vs. 81 % pre-stroke) and peripheral sniffing (∼0 % vs. 9 %). Histological analysis revealed ischemic changes, including nuclear shrinkage, pyknosis, and infarct zones with blood clots. Lesion size ranged from 1 mm² to 18 mm². Ex vivo diffusion MRI showed increased mean kurtosis in three pigs, confirming microstructural changes. Comparison with existing methods and conclusions: The model produced behavioral and histological characteristics in pigs, which have gyrencephalic brains, large intracranial vessel diameters, and a high white-to-gray matter ratio, similar to those observed in other animals and traditional models. This model can produce a reproducible isolated cortical lesion using stereotactic coordinates and/or 3D imaging.

KW - Photothrombosis

KW - Porcine

KW - RoseBengal

KW - Stroke

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U2 - 10.1016/j.jneumeth.2025.110408

DO - 10.1016/j.jneumeth.2025.110408

M3 - Journal article

C2 - 40010647

SN - 0165-0270

VL - 418

JO - Journal of Neuroscience Methods

JF - Journal of Neuroscience Methods

M1 - 110408

ER -

A large animal model for focal stroke: Photothrombotic lesion in the cortex of Danish Landrace pigs

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