Biomedicines

Editorial

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Open AccessEditorial

Porcine Models of Neurotrauma and Neurological Disorders

by John C. O’Donnell and Dmitriy Petrov

Biomedicines 2024, 12(1), 245; https://doi.org/10.3390/biomedicines12010245 - 22 Jan 2024

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Abstract

The translation of therapeutics from lab to clinic has a dismal record in the fields of neurotrauma and neurological disorders [...] Full article

(This article belongs to the Special Issue Porcine Models of Neurotrauma and Neurological Disorders)

Research

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18 pages, 2727 KiB

Open AccessArticle

Persistence of Hyper-Ramified Microglia in Porcine Cortical Gray Matter after Mild Traumatic Brain Injury

by Michael R. Grovola, Alan Jinich, Nicholas Paleologos, Edgardo J. Arroyo, Kevin D. Browne, Randel L. Swanson, John E. Duda and D. Kacy Cullen

Biomedicines 2023, 11(7), 1960; https://doi.org/10.3390/biomedicines11071960 - 12 Jul 2023

Cited by 2 | Viewed by 1411

Abstract

Traumatic brain injury (TBI) is a major contributor to morbidity and mortality in the United States as several million people visit the emergency department every year due to TBI exposures. Unfortunately, there is still no consensus on the pathology underlying mild TBI, the [...] Read more.

Traumatic brain injury (TBI) is a major contributor to morbidity and mortality in the United States as several million people visit the emergency department every year due to TBI exposures. Unfortunately, there is still no consensus on the pathology underlying mild TBI, the most common severity sub-type of TBI. Previous preclinical and post-mortem human studies have detailed the presence of diffuse axonal injury following TBI, suggesting that white matter pathology is the predominant pathology of diffuse brain injury. However, the inertial loading produced by TBI results in strain fields in both gray and white matter. In order to further characterize gray matter pathology in mild TBI, our lab used a pig model (n = 25) of closed-head rotational acceleration-induced TBI to evaluate blood-brain barrier disruptions, neurodegeneration, astrogliosis, and microglial reactivity in the cerebral cortex out to 1 year post-injury. Immunohistochemical staining revealed the presence of a hyper-ramified microglial phenotype—more branches, junctions, endpoints, and longer summed process length—at 30 days post injury (DPI) out to 1 year post injury in the cingulate gyrus (p < 0.05), and at acute and subacute timepoints in the inferior temporal gyrus (p < 0.05). Interestingly, we did not find neuronal loss or astroglial reactivity paired with these chronic microglia changes. However, we observed an increase in fibrinogen reactivity—a measure of blood-brain barrier disruption—predominately in the gray matter at 3 DPI (p = 0.0003) which resolved to sham levels by 7 DPI out to chronic timepoints. Future studies should employ gene expression assays, neuroimaging, and behavioral assays to elucidate the effects of these hyper-ramified microglia, particularly related to neuroplasticity and responses to potential subsequent insults. Further understanding of the brain’s inflammatory activity after mild TBI will hopefully provide understanding of pathophysiology that translates to clinical treatment for TBI. Full article

(This article belongs to the Special Issue Porcine Models of Neurotrauma and Neurological Disorders)

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18 pages, 3166 KiB

Open AccessArticle

Altered Auditory and Visual Evoked Potentials following Single and Repeated Low-Velocity Head Rotations in 4-Week-Old Swine

by Anna Oeur, William H. Torp, Kristy B. Arbogast, Christina L. Master and Susan S. Margulies

Biomedicines 2023, 11(7), 1816; https://doi.org/10.3390/biomedicines11071816 - 25 Jun 2023

Cited by 1 | Viewed by 929

Abstract

Auditory and visually evoked potentials (EP) have the ability to monitor cognitive changes after concussion. In the literature, decreases in EP are commonly reported; however, a subset of studies shows increased cortical activity after injury. We studied auditory and visual EP in 4-week-old [...] Read more.

Auditory and visually evoked potentials (EP) have the ability to monitor cognitive changes after concussion. In the literature, decreases in EP are commonly reported; however, a subset of studies shows increased cortical activity after injury. We studied auditory and visual EP in 4-week-old female Yorkshire piglets (N = 35) divided into anesthetized sham, and animals subject to single (sRNR) and repeated (rRNR) rapid non-impact head rotations (RNR) in the sagittal direction. Two-tone auditory oddball tasks and a simple white-light visual stimulus were evaluated in piglets pre-injury, and at days 1, 4- and 7 post injury using a 32-electrode net. Traditional EP indices (N1, P2 amplitudes and latencies) were extracted, and a piglet model was used to source-localize the data to estimate brain regions related to auditory and visual processing. In comparison to each group’s pre-injury baselines, auditory Eps and brain activity (but not visual activity) were decreased in sham. In contrast, sRNR had increases in N1 and P2 amplitudes from both stimuli. The rRNR group had decreased visual N1 amplitudes but faster visual P2 latencies. Auditory and visual EPs have different change trajectories after sRNR and rRNR, suggesting that injury biomechanics are an important factor to delineate neurofunctional deficits after concussion. Full article

(This article belongs to the Special Issue Porcine Models of Neurotrauma and Neurological Disorders)

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10 pages, 3798 KiB

Open AccessArticle

Exploring the Therapeutic Potential of Phosphorylated Cis-Tau Antibody in a Pig Model of Traumatic Brain Injury

by Samuel S. Shin, Vanessa M. Mazandi, Andrea L. C. Schneider, Sarah Morton, Jonathan P. Starr, M. Katie Weeks, Nicholas J. Widmann, David H. Jang, Shih-Han Kao, Michael K. Ahlijanian and Todd J. Kilbaugh

Biomedicines 2023, 11(7), 1807; https://doi.org/10.3390/biomedicines11071807 - 24 Jun 2023

Cited by 1 | Viewed by 1121

Abstract

Traumatic brain injury (TBI) results in the generation of tau. As hyperphosphorylated tau (p-tau) is one of the major consequences of TBI, targeting p-tau in TBI may lead to the development of new therapy. Twenty-five pigs underwent a controlled cortical impact. One hour [...] Read more.

Traumatic brain injury (TBI) results in the generation of tau. As hyperphosphorylated tau (p-tau) is one of the major consequences of TBI, targeting p-tau in TBI may lead to the development of new therapy. Twenty-five pigs underwent a controlled cortical impact. One hour after TBI, pigs were administered either vehicle (n = 13) or PNT001 (n = 12), a monoclonal antibody for the cis conformer of tau phosphorylated at threonine 231. Plasma biomarkers of neural injury were assessed for 14 days. Diffusion tensor imaging was performed at day 1 and 14 after injury, and these were compared to historical control animals (n = 4). The fractional anisotropy data showed significant white matter injury for groups at 1 day after injury in the corona radiata. At 14 days, the vehicle-treated pigs, but not the PNT001-treated animals, exhibited significant white matter injury compared to sham pigs in the ipsilateral corona radiata. The PNT001-treated pigs had significantly lower levels of plasma glial fibrillary acidic protein (GFAP) at day 2 and day 4. These findings demonstrate a subtle reduction in the areas of white matter injury and biomarkers of neurological injury after treatment with PNT001 following TBI. These findings support additional studies for PNT001 as well as the potential use of this agent in clinical trials in the near future. Full article

(This article belongs to the Special Issue Porcine Models of Neurotrauma and Neurological Disorders)

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17 pages, 8494 KiB

Open AccessArticle

The Central Fluid Percussion Brain Injury in a Gyrencephalic Pig Brain: Scalable Diffuse Injury and Tissue Viability for Glial Cell Immunolabeling following Long-Term Refrigerated Storage

by Mark Pavlichenko and Audrey D. Lafrenaye

Biomedicines 2023, 11(6), 1682; https://doi.org/10.3390/biomedicines11061682 - 10 Jun 2023

Cited by 1 | Viewed by 1325

Abstract

Traumatic brain injury (TBI) affects millions of people annually; however, our knowledge of the diffuse pathologies associated with TBI is limited. As diffuse pathologies, including axonal injury and neuroinflammatory changes, are difficult to visualize in the clinical population, animal models are used. In [...] Read more.

Traumatic brain injury (TBI) affects millions of people annually; however, our knowledge of the diffuse pathologies associated with TBI is limited. As diffuse pathologies, including axonal injury and neuroinflammatory changes, are difficult to visualize in the clinical population, animal models are used. In the current study, we used the central fluid percussion injury (CFPI) model in a micro pig to study the potential scalability of these diffuse pathologies in a gyrencephalic brain of a species with inflammatory systems very similar to humans. We found that both axonal injury and microglia activation within the thalamus and corpus callosum are positively correlated with the weight-normalized pressure pulse, while subtle changes in blood gas and mean arterial blood pressure are not. We also found that the majority of tissue generated up to 10 years previously is viable for immunofluorescent labeling after long-term refrigeration storage. This study indicates that a micro pig CFPI model could allow for specific investigations of various degrees of diffuse pathological burdens following TBI. Full article

(This article belongs to the Special Issue Porcine Models of Neurotrauma and Neurological Disorders)

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13 pages, 1605 KiB

Open AccessArticle

SmartPill™ Administration to Assess Gastrointestinal Function after Spinal Cord Injury in a Porcine Model—A Preliminary Study

by Chase A. Knibbe, Rakib Uddin Ahmed, Felicia Wilkins, Mayur Sharma, Jay Ethridge, Monique Morgan, Destiny Gibson, Kimberly B. Cooper, Dena R. Howland, Manicka V. Vadhanam, Shirish S. Barve, Steven Davison, Leslie C. Sherwood, Jack Semler, Thomas Abell and Maxwell Boakye

Biomedicines 2023, 11(6), 1660; https://doi.org/10.3390/biomedicines11061660 - 07 Jun 2023

Cited by 4 | Viewed by 1551

Abstract

Gastrointestinal (GI) complications, including motility disorders, metabolic deficiencies, and changes in gut microbiota following spinal cord injury (SCI), are associated with poor outcomes. After SCI, the autonomic nervous system becomes unbalanced below the level of injury and can lead to severe GI dysfunction. [...] Read more.

Gastrointestinal (GI) complications, including motility disorders, metabolic deficiencies, and changes in gut microbiota following spinal cord injury (SCI), are associated with poor outcomes. After SCI, the autonomic nervous system becomes unbalanced below the level of injury and can lead to severe GI dysfunction. The SmartPill™ is a non-invasive capsule that, when ingested, transmits pH, temperature, and pressure readings that can be used to assess effects in GI function post-injury. Our minipig model allows us to assess these post-injury changes to optimize interventions and ultimately improve GI function. The aim of this study was to compare pre-injury to post-injury transit times, pH, and pressures in sections of GI tract by utilizing the SmartPill™ in three pigs after SCI at 2 and 6 weeks. Tributyrin was administered to two pigs to assess the influences on their gut microenvironment. We observed prolonged GET (Gastric Emptying Time) and CTT (Colon Transit Time), decreases in contraction frequencies (Con freq) in the antrum of the stomach, colon, and decreases in duodenal pressures post-injury. We noted increases in Sum amp generated at 2 weeks post-injury in the colon, with corresponding decreases in Con freq. We found transient changes in pH in the colon and small intestine at 2 weeks post-injury, with minimal effect on stomach pH post-injury. Prolonged GETs and CTTs can influence the absorptive profile in the gut and contribute to pathology development. This is the first pilot study to administer the SmartPill™ in minipigs in the context of SCI. Further investigations will elucidate these trends and characterize post-SCI GI function. Full article

(This article belongs to the Special Issue Porcine Models of Neurotrauma and Neurological Disorders)

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31 pages, 14908 KiB

Open AccessArticle

Multimodal Neuromonitoring and Neurocritical Care in Swine to Enhance Translational Relevance in Brain Trauma Research

by John C. O’Donnell, Kevin D. Browne, Svetlana Kvint, Leah Makaron, Michael R. Grovola, Saarang Karandikar, Todd J. Kilbaugh, D. Kacy Cullen and Dmitriy Petrov

Biomedicines 2023, 11(5), 1336; https://doi.org/10.3390/biomedicines11051336 - 30 Apr 2023

Cited by 4 | Viewed by 2421

Abstract

Neurocritical care significantly impacts outcomes after moderate-to-severe acquired brain injury, but it is rarely applied in preclinical studies. We created a comprehensive neurointensive care unit (neuroICU) for use in swine to account for the influence of neurocritical care, collect clinically relevant monitoring data, [...] Read more.

Neurocritical care significantly impacts outcomes after moderate-to-severe acquired brain injury, but it is rarely applied in preclinical studies. We created a comprehensive neurointensive care unit (neuroICU) for use in swine to account for the influence of neurocritical care, collect clinically relevant monitoring data, and create a paradigm that is capable of validating therapeutics/diagnostics in the unique neurocritical care space. Our multidisciplinary team of neuroscientists, neurointensivists, and veterinarians adapted/optimized the clinical neuroICU (e.g., multimodal neuromonitoring) and critical care pathways (e.g., managing cerebral perfusion pressure with sedation, ventilation, and hypertonic saline) for use in swine. Moreover, this neurocritical care paradigm enabled the first demonstration of an extended preclinical study period for moderate-to-severe traumatic brain injury with coma beyond 8 h. There are many similarities with humans that make swine an ideal model species for brain injury studies, including a large brain mass, gyrencephalic cortex, high white matter volume, and topography of basal cisterns, amongst other critical factors. Here we describe the neurocritical care techniques we developed and the medical management of swine following subarachnoid hemorrhage and traumatic brain injury with coma. Incorporating neurocritical care in swine studies will reduce the translational gap for therapeutics and diagnostics specifically tailored for moderate-to-severe acquired brain injury. Full article

(This article belongs to the Special Issue Porcine Models of Neurotrauma and Neurological Disorders)

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16 pages, 2287 KiB

Open AccessArticle

Pupillary Light Response Deficits in 4-Week-Old Piglets and Adolescent Children after Low-Velocity Head Rotations and Sports-Related Concussions

by Anna Oeur, Mackenzie Mull, Giancarlo Riccobono, Kristy B. Arbogast, Kenneth J. Ciuffreda, Nabin Joshi, Daniele Fedonni, Christina L. Master and Susan S. Margulies

Biomedicines 2023, 11(2), 587; https://doi.org/10.3390/biomedicines11020587 - 16 Feb 2023

Cited by 3 | Viewed by 1479

Abstract

Neurological disorders and traumatic brain injury (TBI) are among the leading causes of death and disability. The pupillary light reflex (PLR) is an emerging diagnostic tool for concussion in humans. We compared PLR obtained with a commercially available pupillometer in the 4 week [...] Read more.

Neurological disorders and traumatic brain injury (TBI) are among the leading causes of death and disability. The pupillary light reflex (PLR) is an emerging diagnostic tool for concussion in humans. We compared PLR obtained with a commercially available pupillometer in the 4 week old piglet model of the adolescent brain subject to rapid nonimpact head rotation (RNR), and in human adolescents with and without sports-related concussion (SRC). The 95% PLR reference ranges (RR, for maximum and minimum pupil diameter, latency, and average and peak constriction velocities) were established in healthy piglets (N = 13), and response reliability was validated in nine additional healthy piglets. PLR assessments were obtained in female piglets allocated to anesthetized sham (N = 10), single (sRNR, N = 13), and repeated (rRNR, N = 14) sagittal low-velocity RNR at pre-injury, as well as days 1, 4, and 7 post injury, and evaluated against RRs. In parallel, we established human PLR RRs in healthy adolescents (both sexes, N = 167) and compared healthy PLR to values obtained <28 days from a SRC (N = 177). In piglets, maximum and minimum diameter deficits were greater in rRNR than sRNR. Alterations peaked on day 1 post sRNR and rRNR, and remained altered at day 4 and 7. In SRC adolescents, the proportion of adolescents within the RR was significantly lower for maximum pupil diameter only (85.8%). We show that PLR deficits may persist in humans and piglets after low-velocity head rotations. Differences in timing of assessment after injury, developmental response to injury, and the number and magnitude of impacts may contribute to the differences observed between species. We conclude that PLR is a feasible, quantifiable involuntary physiological metric of neurological dysfunction in pigs, as well as humans. Healthy PLR porcine and human reference ranges established can be used for neurofunctional assessments after TBI or hypoxic exposures (e.g., stroke, apnea, or cardiac arrest). Full article

(This article belongs to the Special Issue Porcine Models of Neurotrauma and Neurological Disorders)

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18 pages, 2509 KiB

Open AccessArticle

Multiple Head Rotations Result in Persistent Gait Alterations in Piglets

by Mackenzie Mull, Oluwagbemisola Aderibigbe, Marzieh Hajiaghamemar, R. Anna Oeur and Susan S Margulies

Biomedicines 2022, 10(11), 2976; https://doi.org/10.3390/biomedicines10112976 - 19 Nov 2022

Cited by 4 | Viewed by 1705

Abstract

Multiple/repeated mild traumatic brain injury (mTBI) in young children can cause long-term gait impairments and affect the developmental course of motor control. Using our swine model for mTBI in young children, our aim was to (i) establish a reference range (RR) for each [...] Read more.

Multiple/repeated mild traumatic brain injury (mTBI) in young children can cause long-term gait impairments and affect the developmental course of motor control. Using our swine model for mTBI in young children, our aim was to (i) establish a reference range (RR) for each parameter to validate injury and track recovery, and (ii) evaluate changes in gait patterns following a single and multiple (5×) sagittal rapid non-impact head rotation (RNR). Gait patterns were studied in four groups of 4-week-old Yorkshire swine: healthy (n = 18), anesthesia-only sham (n = 8), single RNR injury (n = 12) and multiple RNR injury (n = 11). Results were evaluated pre-injury and at 1, 4, and 7 days post-injury. RR reliability was validated using additional healthy animals (n = 6). Repeated mTBI produced significant increases in gait time, cycle time, and stance time, as well as decreases in gait velocity and cadence, on Day One post-injury compared to pre-injury, and these remained significantly altered at Day Four and Day Seven post-injury. The gait metrics of the repeated TBI group also significantly fell outside the healthy RR on Day One, with some recovery by Day Four, while many remained altered at Day Seven. Only a bilateral decrease in hind stride length was observed at Day Four in our single RNR group compared to pre-injury. In sum, repeated and single sagittal TBI can significantly impair motor performance, and gait metrics can serve as reliable, objective, quantitative functional assessments in a juvenile porcine RNR TBI model. Full article

(This article belongs to the Special Issue Porcine Models of Neurotrauma and Neurological Disorders)

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16 pages, 1443 KiB

Open AccessArticle

A Touchscreen Device for Behavioral Testing in Pigs

by Will Ao, Megan Grace, Candace L. Floyd and Cole Vonder Haar

Biomedicines 2022, 10(10), 2612; https://doi.org/10.3390/biomedicines10102612 - 18 Oct 2022

Cited by 2 | Viewed by 1480

Abstract

Pigs are becoming more common research models due to their utility in studying neurological conditions such as traumatic brain injury, Alzheimer’s disease, and Huntington’s Disease. However, behavioral tasks often require a large apparatus and are not automated, which may disinterest researchers in using [...] Read more.

Pigs are becoming more common research models due to their utility in studying neurological conditions such as traumatic brain injury, Alzheimer’s disease, and Huntington’s Disease. However, behavioral tasks often require a large apparatus and are not automated, which may disinterest researchers in using important functional measures. To address this, we developed a touchscreen that pigs could be trained on for behavioral testing. A rack-mounted touchscreen monitor was placed in an enclosed, weighted audio rack. A pellet dispenser was operated by a radio frequency transceiver to deliver fruit-flavored sugar pellets from across the testing room. Programs were custom written in Python and executed on a microcomputer. A behavioral shaping program was designed to train pigs to interact with the screen and setup responses for future tasks. Pigs rapidly learned to interact with the screen. To demonstrate efficacy in more complex behavior, two pigs were trained on a delay discounting tasks and two pigs on a color discrimination task. The device held up to repeated testing of large pigs and could be adjusted to the height of minipigs. The device can be easily recreated and constructed at a relatively low cost. Research topics ranging from brain injury to pharmacology to vision could benefit from behavioral tasks designed to specifically interrogate relevant function. More work will be needed to develop tests which are of specific relevance to these disciplines. Full article

(This article belongs to the Special Issue Porcine Models of Neurotrauma and Neurological Disorders)

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Review

Jump to: Editorial, Research

30 pages, 2058 KiB

Open AccessReview

Porcine Astrocytes and Their Relevance for Translational Neurotrauma Research

by Erin M. Purvis, Natalia Fedorczak, Annette Prah, Daniel Han and John C. O’Donnell

Biomedicines 2023, 11(9), 2388; https://doi.org/10.3390/biomedicines11092388 - 26 Aug 2023

Cited by 1 | Viewed by 987

Abstract

Astrocytes are essential to virtually all brain processes, from ion homeostasis to neurovascular coupling to metabolism, and even play an active role in signaling and plasticity. Astrocytic dysfunction can be devastating to neighboring neurons made inherently vulnerable by their polarized, excitable membranes. Therefore, [...] Read more.

Astrocytes are essential to virtually all brain processes, from ion homeostasis to neurovascular coupling to metabolism, and even play an active role in signaling and plasticity. Astrocytic dysfunction can be devastating to neighboring neurons made inherently vulnerable by their polarized, excitable membranes. Therefore, correcting astrocyte dysfunction is an attractive therapeutic target to enhance neuroprotection and recovery following acquired brain injury. However, the translation of such therapeutic strategies is hindered by a knowledge base dependent almost entirely on rodent data. To facilitate additional astrocytic research in the translatable pig model, we present a review of astrocyte findings from pig studies of health and disease. We hope that this review can serve as a road map for intrepid pig researchers interested in studying astrocyte biology. Full article

(This article belongs to the Special Issue Porcine Models of Neurotrauma and Neurological Disorders)

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15 pages, 304 KiB

Open AccessReview

Porcine Models of Spinal Cord Injury

by Connor A. Wathen, Yohannes G. Ghenbot, Ali K. Ozturk, D. Kacy Cullen, John C. O’Donnell and Dmitriy Petrov

Biomedicines 2023, 11(8), 2202; https://doi.org/10.3390/biomedicines11082202 - 04 Aug 2023

Cited by 1 | Viewed by 1202

Abstract

Large animal models of spinal cord injury may be useful tools in facilitating the development of translational therapies for spinal cord injury (SCI). Porcine models of SCI are of particular interest due to significant anatomic and physiologic similarities to humans. The similar size [...] Read more.

Large animal models of spinal cord injury may be useful tools in facilitating the development of translational therapies for spinal cord injury (SCI). Porcine models of SCI are of particular interest due to significant anatomic and physiologic similarities to humans. The similar size and functional organization of the porcine spinal cord, for instance, may facilitate more accurate evaluation of axonal regeneration across long distances that more closely resemble the realities of clinical SCI. Furthermore, the porcine cardiovascular system closely resembles that of humans, including at the level of the spinal cord vascular supply. These anatomic and physiologic similarities to humans not only enable more representative SCI models with the ability to accurately evaluate the translational potential of novel therapies, especially biologics, they also facilitate the collection of physiologic data to assess response to therapy in a setting similar to those used in the clinical management of SCI. This review summarizes the current landscape of porcine spinal cord injury research, including the available models, outcome measures, and the strengths, limitations, and alternatives to porcine models. As the number of investigational SCI therapies grow, porcine SCI models provide an attractive platform for the evaluation of promising treatments prior to clinical translation. Full article

(This article belongs to the Special Issue Porcine Models of Neurotrauma and Neurological Disorders)

15 pages, 1709 KiB

Open AccessReview

The Pig as a Translational Animal Model for Biobehavioral and Neurotrauma Research

by Alesa H. Netzley and Galit Pelled

Biomedicines 2023, 11(8), 2165; https://doi.org/10.3390/biomedicines11082165 - 01 Aug 2023

Cited by 1 | Viewed by 1473

Abstract

In recent decades, the pig has attracted considerable attention as an important intermediary model animal in translational biobehavioral research due to major similarities between pig and human neuroanatomy, physiology, and behavior. As a result, there is growing interest in using pigs to model [...] Read more.

In recent decades, the pig has attracted considerable attention as an important intermediary model animal in translational biobehavioral research due to major similarities between pig and human neuroanatomy, physiology, and behavior. As a result, there is growing interest in using pigs to model many human neurological conditions and injuries. Pigs are highly intelligent and are capable of performing a wide range of behaviors, which can provide valuable insight into the effects of various neurological disease states. One area in which the pig has emerged as a particularly relevant model species is in the realm of neurotrauma research. Indeed, the number of investigators developing injury models and assessing treatment options in pigs is ever-expanding. In this review, we examine the use of pigs for cognitive and behavioral research as well as some commonly used physiological assessment methods. We also discuss the current usage of pigs as a model for the study of traumatic brain injury. We conclude that the pig is a valuable animal species for studying cognition and the physiological effect of disease, and it has the potential to contribute to the development of new treatments and therapies for human neurological and psychiatric disorders. Full article

(This article belongs to the Special Issue Porcine Models of Neurotrauma and Neurological Disorders)

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