Porcine Stroke Models
At a glance
Modeling stroke in animals provides an important platform for studying disease and developing therapy, and a number of stroke animal models have been developed. Pig is considered excellent for modeling stroke because it has a relatively large gyrencephalic brain, only seven times smaller than human brain and stroke white–gray matter ratio and immune system closely resembles that of human. In addition, the subarachnoid space around the pig brain is similar to that of humans. This allows blood and clots to accumulate in the subarachnoid hemorrhage model, simulating clinical conditions.
At Ace Therapeutics, we provide customized porcine stroke models to help our clients study the pathophysiology of stroke and develop new therapies.
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Pig Brain to Model Human Stroke Pathophysiology
Among large animal stroke models with translational advantages, non-human primates (NHPs) are very close to humans but have ethical challenges, while canines are socially controversial as companion animals and are no longer allowed to be used in experiments in many countries. In contrast, pigs, commonly used in the meat industry, do not present the same ethical dilemmas for most people, making them a more acceptable choice for research.
Unlike rodents, pigs have highly gyrencephalic brains, resembling the lobes, gyri, and sulci of human brains. Their brain organization, including motor and somatosensory areas, is comparable to other mammals, and many brain structures, such as the limbic system and brainstem, are similar to humans. Pigs also have a brain mass similar to or larger than commonly used non-human primates, with a well-developed prefrontal cortex. Their brain development, including myelination, is similar to humans, and they exhibit comparable resting-state networks and connectivity. Due to their fibrous dura mater, pigs experience intracranial pressure changes similar to humans in stroke, and their brains can be studied using the same imaging techniques used in clinical practice. Pigs also demonstrate complex behaviors and social interactions, and their neurovascular characteristics make them suitable for pre-clinical testing of neurosurgical techniques and endovascular devices.
Pigs have a higher ratio of white matter (WM) to gray matter compared to rodents, with a WM composition similar to humans, making them more suitable for studying brain connectivity and stroke pathophysiology. The failure of neuroprotective treatments in stroke clinical trials may be partly due to the use of rodents, which lack relevant brain characteristics. These factors make pigs an excellent model for translating research into clinical applications.
Fig.1. Pig and rat brain hemispheres showing differences in size and gyrencephaly. (Melià-Sorolla, et al., 2020)
Porcine Ischemic Stroke Models
| Methods | Target | Advantages | Disadvantages |
|---|---|---|---|
| Electrocoagulation | MCA ICA AChA MCA + ICA |
|
This technique leads to irreversible occlusion of the vessel, preventing reperfusion of the infarcted tissue. |
| Microvascular Clip | MCA |
|
Extremely aggressive approach |
| Endovascular Embolization | Extracranial arteries CCA APA ICA Rete mirabile APA-rete mirabile |
|
The presence of a micromesh avoids the possibility of reaching the intracranial vessels through an endovascular route. |
| Photothrombosis | MCA |
|
Photothrombosis of intracranial arteries in pigs requires exposure of the target vessel through a transorbital approach or craniotomy, a more invasive procedure. |
| ET-1 Injection | MCA |
|
Invasive approach |
Porcine Hemorrhagic Stroke Models
| Methods | Target | Advantages | Disadvantages |
|---|---|---|---|
| Autologous Blood Injection in Meningeal Spaces | Subarachnoid space Cisterna magna (subarachnoid space) Pontine cistern (subarachnoid space) |
Reproducible | Invasive |
| Intracerebral Autologous Blood Injection | Brain parenchyma | Reproducible | Invasive |
| Sonographic Blood-Brain Barrier Disruption | Brain parenchyma |
|
Target limitation |
| Intracerebral Collagenase Injection | Brain parenchyma | Reproducible |
|
Neurological Function Assessment in Pigs
The cognitive abilities of pigs have been studied using different methods. Several tasks and maze tests adapted to pigs have been developed to assess different cognitive and behavioral aspects, such as memory and learning, emotional behavior, or social interaction.
| Learning and Memory Assessment | Cognitive Tasks |
|---|---|
|
|
Evaluation of Stroke Damage in Swine by Neuroimaging
Techniques like magnetic resonance imaging (MRI), positron emission tomography (PET), computed tomography perfusion (CTP), and diffusion-weighted imaging (DWI) are employed to evaluate stroke progression, including parameters like hypoperfusion, infarct core, and penumbra. Conventional MRI sequences (T1, T2, FLAIR) help identify infarct volume, edema, and cytotoxic damage. More advanced methods, such as diffusion tensor imaging (DTI), are used to study white matter integrity, with findings showing WM loss in stroke-affected areas. For hemorrhagic stroke, CT and MRI are used to measure blood leakage and hematoma, with techniques like dynamic contrast-enhanced MRI helping track hematoma growth.
Additionally, emerging imaging biomarkers, including magnetization transfer imaging (MTI) and MR spectroscopy, have the potential to enhance personalized stroke treatment by revealing microstructural damage and metabolic changes in affected areas. These imaging tools provide valuable information for understanding stroke pathophysiology and evaluating therapeutic interventions.
Fig.2. Diffusion changes after stroke induction in pigs. (Golubczyk, et al., 2020)
- Melià-Sorolla, M., et al. (2020). Relevance of porcine stroke models to bridge the gap from pre-clinical findings to clinical implementation. International journal of molecular sciences, 21(18), 6568.
- Golubczyk, D., et al. (2020). Endovascular model of ischemic stroke in swine guided by real-time MRI. Scientific reports, 10(1), 17318.
