Swine as a Animal Model for Traumatic Brain Injury, Stroke, and Neurodegenerative Disease

While swine have historically not been used as a model for the human central nervous system due to their enormous skull bones and vertebrae and very narrow intervertebral spacing, their appearance in the neuroscience literature has been rapidly increasing. Swine have relatively large brains that are anatomically more similar to humans than rodents in that they are gyrencephalic, contain more white matter, and have similar patterns of cerebral blood flow. [1]

Because swine also display a very human-like progression of early brain development, neonatal swine have become a particularly interesting new model of pediatric traumatic brain injury (TBI) and stroke. TBI is characterized by primary distortion of the parenchyma and secondary excitotoxicity, cell death, axonal injury, cerebral swelling, and inflammation. Swine and human responses to TBI are very similar and have been well characterized in terms of arterial and intracranial pressures, cerebral blood flow, histopathology, and a variety of other measures. Further, simple functional testing using a veterinary coma scale and complex neurobehavioral testing to assess functional outcome of TBI-treated swine are documented. This enables researchers to determine whether novel neuroprotective therapies offer significant improvement in neurological outcomes. [11] Ischemic stroke in pediatric patients is mechanistically different than observed in adults and thus suggests treatment regimens be age-specific. However, there is still relatively little known about stroke in children as options for animal models have been limiting. A new neonatal swine model reliably produces clinically-relevant ischemic stroke in both grey and white matter that upon histopathological analysis shows evidence of platelet activation, thrombus formation, apoptosis, and localized accumulation of inflammatory leukocytes. The model also, as a result of the large size of piglets relative to rat pups for example, facilitates collection of other important physiological measurements including blood pressure and oxygen saturation. [12]

Large animal models are particularly important for the study of human neurodegenerative diseases as rodent models cannot approximate the size and gross anatomy of human brains much less their neuroanatomical connectivity and cognitive capacity. Monkey and swine are the most human-like neurological models described to date and are critical for bridging the gap in neurodegenerative disease research between basic discovery science performed in rodents and clinical trials for human therapeutics. Swine models of Parkinson’s disease (PD) and Huntington’s disease (HD) have been extensively studied and recently been used for the production of xenografts that are already in clinical trials. [13] Advances in swine genomics have resulted in the development of transgenic swine models of several other neurodegenerative diseases including HD, Alzheimer’s disease (AD), and retinitis pigmentosa (RP). The transgenic swine HD model expresses mutant swine huntington protein (HTT) while the AD model expresses mutant human amyloid precursor protein (APP). Neither of these models have yet been fully characterized as functional deficits will only appear as the animals age. The transgenic swine RP model expresses mutant swine rhodopsin protein (RHO) and as a result is afflicted, like humans, with early and near complete degeneration of rod photoreceptors followed by a more protracted deterioration of cone photoreceptors. [2]

References

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