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. 2021 Aug 6;240(1):172–181. doi: 10.1111/joa.13525

Brachial plexus anatomy in the miniature swine as compared to human

Amgad S Hanna 1,✉, Daniel J Hellenbrand 1, Dominic T Schomberg 2, Shahriar M Salamat 1,3, Megan Loh 1, Lea Wheeler 1, Barbara Hanna 4, Burak Ozaydin 1, Jennifer Meudt 5, Dhanansayan Shanmuganayagam 2,6
PMCID: PMC8655215  PMID: 34355792

Abstract

Brachial plexus injury (BPI) occurs when the brachial plexus is compressed, stretched, or avulsed. Although rodents are commonly used to study BPI, these models poorly mimic human BPI due to the discrepancy in size. The objective of this study was to compare the brachial plexus between human and Wisconsin Miniature SwineTM (WMSTM), which are approximately the weight of an average human (68–91 kg), to determine if swine would be a suitable model for studying BPI mechanisms and treatments. To analyze the gross anatomy, WMS brachial plexuses were dissected both anteriorly and posteriorly. For histological analysis, sections from various nerves of human and WMS brachial plexuses were fixed in 2.5% glutaraldehyde, and postfixed with 2% osmium tetroxide. Subsequently paraffin sections were counter‐stained with Masson's Trichrome. Gross anatomy revealed that the separation into three trunks and three cords is significantly less developed in the swine than in human. In swine, it takes the form of upper, middle, and lower systems with ventral and dorsal components. Histological evaluation of selected nerves revealed differences in nerve trunk diameters and the number of myelinated axons in the two species. The WMS had significantly fewer myelinated axons than humans in median (p = 0.0049), ulnar (p = 0.0002), and musculocutaneous nerves (p = 0.0454). The higher number of myelinated axons in these nerves for humans is expected because there is a high demand of fine motor and sensory functions in the human hand. Due to the stronger shoulder girdle muscles in WMS, the WMS suprascapular and axillary nerves were larger than in human. Overall, the WMS brachial plexus is similar in size and origin to human making them a very good model to study BPI. Future studies analyzing the effects of BPI in WMS should be conducted.

Keywords: anatomy, avulsion, brachial plexus, nerve injury, swine

The WMS brachial plexus is similar in size and origin to human making them a very good model to study brachial plexus injury.

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1. INTRODUCTION

The brachial plexus is a network of nerves formed by the ventral rami of the four lower cervical nerves (C5, C6, C7, C8) and the first thoracic nerve (T1), with some variability amongst different species. Brachial plexus injury (BPI) is a nerve injury defined by loss of function in one or both upper limbs resulting from partial or complete denervation of muscles. A BPI may occur when this network of nerves is compressed, stretched, or, in more serious cases, avulsed. Approximately 1.2% of multi‐trauma patients suffer from some form of BPI, and the majority of these injuries are caused by high velocity traffic collisions (Midha, 1997). Adult patients with BPI are, on average, young men between the ages of 25 and 29 and go on to suffer socioeconomic disadvantages, physical disabilities, and a decreased quality of life (Gilbert et al., 1999; Krishnan et al., 2008; Moiyadi et al., 2007).

BPI can restrict upper limb function in a variety of ways. Injury to C5–C6 nerves causes loss of elbow flexion, shoulder abduction, and external rotation. Deficits in movements of the fingers and wrist indicate involvement of C7 and C8 spinal nerves (Ali et al., 2016). Sensory and motor deficits are accompanied by neuropathic pain in up to 95% of BPIs and can be extremely debilitating (Bruxelle et al., 1988; Vannier et al., 2008). Secondary signaling cascades, including inflammation, oxidative stress, blood–spinal cord barrier disruption, and scar formation, further exacerbate the injury and negatively impact recovery (Blits et al., 2004; Guo et al., 2019; Ham & Leipzig, 2018; Yang et al., 2015).

Treatment for BPI has been unsatisfactory due to the complexity of the injury and the lack of specific treatments (Chuang, 2010). Brachial plexus avulsion (BPA) is a preganglionic lesion and is the most severe form of BPI; it is extremely difficult to treat (Midha, 2004). Current treatment methods of BPI include distal nerve transfers, brachial plexus exploration, nerve grafting from residual nerves, free muscle transfers, and tendon transfers (Gao et al., 2018). Despite recent advances in nerve repair techniques, the prognosis of BPA, especially panplexus injuries, is generally poor (Ali et al., 2016; Gao et al., 2018).

Highly translatable animal models are required to recapitulate the anatomy and complex pathophysiology associated with BPI. Rats and mice are the most‐often studied animal model and represent a majority of scientific literature (Zurita et al., 2012). These models are low cost, have well‐established analysis methods, and have easily manageable husbandry. However, these studies fail to produce satisfactory results in human clinical trials, probably due to differences in size, physiological responses, and anatomy (Lee et al., 2013). Lack of comparative studies on descending neural pathways, differences in segmental injury distribution, and difficulty estimating international treatment standards also contribute to the failure of clinical trials (Dietz & Curt, 2012; Schomberg et al., 2017). These limitations may be more easily overcome with a better intermediary animal model. Larger animals such as swine have shown to be a valuable translational resource for modeling more complex pathophysiology. Similarities in body size, physiological responses, and anatomical dimensions to humans make swine a very good translational model (Dolezalova et al., 2014). Conventional breeds of pigs typically reach 100 kg by 4 months of age and 249–306 kg at full maturity and are impractical for use in long‐term studies. In contrast, the Wisconsin Miniature Swine™ (WMS™) range from 25 to 50 kg at 4 months of age and 68–91 kg at full maturity, approximating the weight of an average human, and can be maintained at adult human size for years (Schomberg et al., 2017). The low cost, short gestation interval, and high availability of swine are also advantages over the non‐human primate models that are traditionally more costly. Swine share 10 times the number of orthologous gene families with humans compared with rodent models and have an analogous post‐injury inflammatory marker profile (Dawson et al., 2013; Hou et al., 2013). Similarities between swine and humans in dietary structure, kidney function, respiratory rates, and social behaviors further advance their suitablility as a medical animal model (Tumbleson & Schook, 1996). Swine have more recently been used for translational research in cardiology, diabetes, traumatic brain injury, and spinal cord injury (Stern et al., 2009; Torres‐Rovira et al., 2012; Wilson et al., 2017, 2021). The purpose of this study is to perform an in‐depth anatomical comparison of the brachial plexus between humans and WMS to determine suitability as a model for BPI treatment research. All experiments involving animals were conducted under protocols approved by the University of Wisconsin – Madison Institutional Animal Care and Use Committee (IACUC) in accordance with published NIH and USDA guidelines.

2. METHODS

2.1. Swine dissection

Six male WMS (weight = 76.8 kg ± 1.22 kg; age = 502 ± 1 days) bred and maintained at the Swine Research and Teaching Center (SRTC; University of Wisconsin‐Madison) were euthanized and 10 brachial plexuses were dissected. Euthanasia started with sedation using TELAZOL®/xylazine, anesthesia with isoflurane, then intracardiac administration of saturated potassium chloride solution. These were exposed both anteriorly and posteriorly. Anterior exposure was done through an axillary incision. After cutting the pectoral muscles, the forelimb was abducted for full exposure of the brachial plexus. Posterior exposure was performed through a cervicothoracic laminectomy and resection of the paraspinal muscles. Research was done with strict adherence to IACUC (Institutional Animal Care and Use Committee) protocols.

2.2. Histological analysis

Samples of median, ulnar, musculocutaneous, radial, axillary, and suprascapular nerves were harvested from WMS (75.1 ± 1.91 kg), and for comparison nerves were obtained from four fresh human cadavers, and a suprascapular nerve was taken from a formalin‐fixed cadaver (Table 1). Since post‐processing steps can cause the tissue to shrink (Fox et al., 1985) we made sure all fixation and processing steps were consistent for both WMS nerves and fresh human nerves. For fixation, all nerve segments were submerged in 0.1 M PBS, containing 2.5% glutaraldehyde, for a minimum of 24 h. To view myelinated axons, 1 mm nerve segments were rinsed twice in 1× PBS, placed in 2% osmium tetroxide in 1× PBS for 2 h, dehydrated in ethanol, and paraffin‐embedded (Di Scipio et al., 2008). The paraffin‐embedded segments were then sectioned transversely 5 µm thick and placed on glass slides. Tissue sections were counter‐stained with Masson's Trichrome (Sigma) and cover‐slipped with Permount. Two sections from each nerve segment were not counterstained and left with only the osmium tetroxide fixation for counting myelinated axons. Autopsy consents were obtained as appropriately indicated.

TABLE 1.

Histological specimen details

Specimen Age Samples Underlying conditions
Human male 57 years Median, ulnar, musculocutaneous Patient had hepatitis C
Human female 61 years Median, ulnar, musculocutaneous Patient had neuropathy
Human male 34 years Median, ulnar, musculocutaneous None
Human male 60 years Radial, Axillary, suprascapular Patient was obese
WMS male 493 days Median, ulnar, musculocutaneous, suprascapular None
WMS female 495 days Median, ulnar, musculocutaneous, suprascapular None
WMS male 499 days Median, ulnar, musculocutaneous, suprascapular None
WMS male 482 days Radial, Axillary Castrated
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WMS, Wisconsin Miniature Swine.

All sections were imaged under the same parameters at 20× on a Keyence BZ‐9000. Assessment of the myelinated axons was conducted using the Keyence BZ‐II Analyzer software. The same threshold for all images was used, the axons were filled, and the total area of each myelinated axon was recorded. Only myelinated axons larger than 1 µm in diameter were analyzed. Nerve trunk cross‐sectional area was measured by outlining the epineurium using ImageJ and the fascicle cross‐sectional area by outlining the perineurium using ImageJ.

2.3. Statistics

All statistical analyses were performed using Prism 6 (GraphPad Software). One‐way ANOVA was used to compare multiple groups and the unpaired, two‐tailed Student's t‐test was used to compare human to WMS. Statistics for fascicle cross‐sectional area and axon cross‐sectional area were performed as a compilation of all measured in WMS compared with all measured in human. Differences were considered significant at p < 0.05. Quantitative data are presented as mean ± standard error of the mean (SEM).

3. RESULTS

3.1. Gross anatomy

The WMS skeleton does not have a clavicle. The spinous processes of C3–C6 are short and C7 is longer, but T1 is considerably longer and is a very important landmark. One unique feature of the cervical vertebrae is the presence of a ventral branch of the transverse process that covers the most proximal part of the brachial plexus anteriorly. Distal to the spinal ganglion, the spinal nerves divide into ventral and dorsal rami that exit the spinal canal through separate foramina. The brachial plexus is formed mainly by the ventral rami of C6–C8 with a smaller contribution from C5, and T1. The separation into three trunks and three cords is significantly more simplified in the WMS. There are upper (rostral), middle, and lower (caudal) systems with ventral and dorsal components (Figures 1 and 2). The upper system predominantly arises from C6 with some contribution from C5 and goes primarily to the suprascapular nerve. The middle system is mainly C7 and supplies the axillary nerve. The lower system is predominantly C8 with some contribution from T1 and is the main supply to the distal forelimb through the median and ulnar nerves as its ventral components, as well as the radial nerve as its dorsal component. An interesting finding is that the three systems are tightly interconnected with side branches, making it difficult to decide on the exact spinal level contribution to each nerve. Numerous pectoral nerves arise proximally to supply the robust pectoral muscles. The suprascapular nerve has the largest diameter, while the musculocutaneous nerve has the smallest. The latter has dual origin, typically from C7 and C8.

FIGURE 1.

FIGURE 1

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(a) Anterior exposure of the swine right brachial plexus. The swine model lacks the presence of a clavicle. The separation into three trunks and three cords is significantly less developed in the swine. There is rather upper (rostral) (C6), middle (C7), and lower (caudal) (C8) systems with ventral and dorsal components. (b) Left human brachial plexus, anterior view, the clavicle has been removed. UT, upper trunk; MT, middle trunk; LT, lower trunk; S, suprascapular; PC, posterior cord; LC, lateral cord; MC, medial cord; MCu, musculocutaneous; M, median; U, ulnar; A, axillary artery [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 2.

FIGURE 2

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(a) Diagrammatic representation of the swine brachial plexus. Pec, pectora. Copyright Amgad Hanna. Published with permission. (b) Diagram of the human brachial plexus. DS, dorsal scapular; Lt, long thoracic; UT, upper trunk; MT, middle trunk; LT, lower trunk; SC, subclavius; S, suprascapular; PC, posterior cord; LC, lateral cord; MC, medial cord; U&L Ssc, upper and lower subscapular; TD, thoracodorsal; Ax, axillary; R, radial; LP, lateral pectoral; MCu, musculocutaneous; M, median; U, ulnar; MP, medial pectoral; MBC, medial brachial cutaneous; MABC, medial antebrachial cutaneous. Reproduced from. Hanna: The SPA arrangement of the branches of the upper trunk of the brachial plexus: a correction of a long‐standing misconception and a new diagram of the brachial plexus. J Neurosurg 125:350–354, 2016. Copyright Amgad Hanna. Published with permission. Note that the arrangement into trunks and cords is not as obvious in the swine, there are rather upper (rostral), middle, and lower (caudal) systems [Colour figure can be viewed at wileyonlinelibrary.com]

3.2. Histology

The median nerves were not significantly different in size between the WMS and human (WMS = 10.29 ± 0.94 mm2, Human = 9.99 ± 0.59 mm2, p = 0.7986). The fascicles in the WMS median nerve were significantly smaller in cross‐sectional area (WMS = 0.118 ± 0.008 mm2, Human = 0.366 ± 0.09 mm2, p = 0.0005) and greater in number (WMS = 25.33 ± 2.40, Human = 14.67 ± 2.60, p = 0.0395). The WMS median nerves had significantly fewer myelinated axons than human median nerves (WMS = 19,991 ± 2280, Human = 33,958 ± 988, p = 0.0049), and the cross‐sectional area of the axons in the WMS was significantly larger (WMS =52.89 ± 0.201 µm2, Human =43.75 ± 0.1138 µm2, p < 0.0001) (Figures 3 and 9).

FIGURE 3.

FIGURE 3

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Median nerve, WMS (a) and human (b) revealing fascicular organization with corresponding higher magnifications displaying myelinated axons in an individual fascicle. Osmium‐fixed nerves, counter‐stained with Masson's Trichrome. Scale bars: 500 µm on whole nerve images and 50 µm on higher magnification images [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 9.

FIGURE 9

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Comparison of brachial plexus nerves. The specimens listed in (a) were evaluated for the data in each corresponding column. Cross‐sectional area of fascicles in WMS was significantly smaller in all nerves except for musculocutaneous nerve (b). In WMS nerves the trend is for a larger number of fascicles than in human (c). Distribution of mean axon size for different nerves in both human and WMS is reflected in (d). With the exception of axillary nerve, aggregate axon sizes were significantly larger in WMS vs human (e). The human median, ulnar, and musculocutaneous nerves contained significantly more axons than the corresponding WMS nerves (f). Cross‐sectional area of each nerve trunk is reflected in (g), suggesting smaller radial, suprascapular, and axillary nerves in human. One‐way ANOVA was used to compare multiple groups and the Student's T‐test was used to compare WMS with human. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, error bars represent ± SEM

WMS ulnar nerves were significantly larger than human ulnar nerves (WMS = 7.24 ± 0.11 mm2, Human = 6.61 ± 0.13 mm2, p = 0.0190). The number of fascicles was not significantly different between WMS and human ulnar nerves (WMS = 22.33 ± 1.202, Human = 18.33 ± 2.603, p = 0.2355); however, the cross‐sectional area of the fascicles was significantly smaller in the WMS ulnar nerve than in human ulnar nerves (WMS = 0.094 ± 0.006 mm2, Human =0.174 ± 0.023 mm2, p = 0.0004). Although the WMS ulnar nerves had significantly fewer myelinated axons than human ulnar nerves (WMS =16,725 ± 521, Human =24,449 ± 284, p = 0.0002), the cross‐sectional area of the axons in WMS ulnar nerves was significantly larger (WMS =43.08 ± 0.199 µm2, Human =34.07 ± 0.101 µm2, p < 0.0001) (Figures 4 and 9).

FIGURE 4.

FIGURE 4

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Ulnar nerve, WMS (a) and human (b) revealing fascicular organization with corresponding higher magnifications displaying myelinated axons in an individual fascicle. Osmium‐fixed nerves, counter‐stained with Masson's Trichrome. Scale bars: 500 µm on whole nerve images and 50 µm on higher magnification images [Colour figure can be viewed at wileyonlinelibrary.com]

The musculocutaneous nerves were not significantly different in size between the WMS and human (WMS = 2.66 ± 0.17 mm2, Human = 1.99 ± 0.39 mm2, p = 0.1958). The fascicles in the musculocutaneous nerves were similar in the WMS and human, both in terms of cross‐sectional area of the fascicles (WMS = 0.060 ± 0.009 mm2, Human = 0.055 ± 0.008 mm2, p = 0.6556) and the number of fascicles (WMS = 9.333 ± 0.667, Human = 8.333 ± 0.882, p = 0.4169). The WMS musculocutaneous nerves had significantly fewer myelinated axons than human musculocutaneous nerves (WMS = 2237 ± 159, Human =4934 ± 926, p = 0.0454), and the cross‐sectional area of the axons in WMS musculocutaneous nerves was significantly larger (WMS =69.03 ± 0.639 µm2, Human = 24.82 ± 0.203 µm2, p < 0.0001) (Figures 5 and 9).

FIGURE 5.

FIGURE 5

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Musculocutaneous nerve, WMS (a) and human (b) revealing fascicular organization with corresponding higher magnifications displaying myelinated axons in an individual fascicle. Osmium‐fixed nerves, counter‐stained with Masson's Trichrome. Scale bars: 500 µm on whole nerve images and 50 µm on higher magnification images [Colour figure can be viewed at wileyonlinelibrary.com]

The WMS suprascapular nerves were significantly larger than human suprascapular nerves (WMS = 13.77 ± 0.187 mm2, Human = 5.99 ± 1.65 mm2, p = 0.0091). Cross‐sectional area of the fascicles in the WMS suprascapular nerves was significantly smaller than fascicles in human suprascapular nerves (WMS = 0.044 ± 0.003 mm2, Human = 0.128 ± 0.065 mm2, p = 0.0002); however, the number of fascicles was not significantly different between WMS and human suprascapular nerves (WMS = 46.33 ± 11.98, Human = 6.5 ± 4.5, p = 0.0864). Although there was no significant difference in the number of myelinated axons between WMS suprascapular nerves and human suprascapular nerves (WMS = 9990 ± 1263, Human = 6781 ± 1490, p = 0.2022), the cross‐sectional area of the axons in WMS suprascapular nerves was significantly larger (WMS = 78.98 ± 0.505 µm2, Human = 22.36 ± 0.195 µm2, p < 0.0001) (Figures 6 and 9).

FIGURE 6.

FIGURE 6

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Suprascapular nerve, WMS (a) and human (b) revealing fascicular organization with corresponding higher magnifications displaying myelinated axons in an individual fascicle. Osmium‐fixed nerves, counter‐stained with Masson's Trichrome. Scale bars: 500 µm on whole nerve images and 50 µm on higher magnification images [Colour figure can be viewed at wileyonlinelibrary.com]

The radial nerve appeared much larger in WMS (WMS = 18.89 mm2, Human = 5.081 mm2) with more fascicles (WMS = 37, Human = 2) that were significantly smaller in cross‐sectional area (WMS = 0.070 ± 0.008 mm2, Human = 1.78 ± 0.682 mm2, p < 0.0001) as compared with the human radial nerve. The WMS radial nerve also had more myelinated axons (WMS = 23,228, Human = 14,004) that were significantly larger in cross‐sectional area (WMS = 32.20 ± 0.248 µm2, Human = 27.70 ± 0.208 µm2, p < 0.0001) as compared with the human radial nerve (Figures 7 and 9).

FIGURE 7.

FIGURE 7

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Radial nerve, WMS (a) and human (b) revealing fascicular organization with corresponding higher magnifications displaying myelinated axons in an individual fascicle. Osmium‐fixed nerves, counter‐stained with Masson's Trichrome. Scale bars: 500 µm on whole nerve images and 50 µm on higher magnification images [Colour figure can be viewed at wileyonlinelibrary.com]

Similar to the radial nerve, the axillary nerve appeared much larger in WMS (WMS = 13.99 mm2, Human = 2.29 mm2) with more fascicles (WMS = 26, Human = 3) that were significantly smaller in cross‐sectional area (WMS = 0.061 ± 0.010 mm2, Human = 0.3067 ± 0.231 mm2, p < 0.0001) as compared with the human axillary nerve. The WMS axillary nerve had more myelinated axons (WMS = 12,463, Human = 3068) that were not significantly different in cross‐sectional area (WMS =36.09 ± 0.359 µm2, Human = 35.39 ± 0.499 µm2, p = 0.3591) as compared with the human axillary nerve (Figures 8 and 9).

FIGURE 8.

FIGURE 8

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Axillary nerve, WMS (a) and human (b) revealing fascicular organization with corresponding higher magnifications displaying myelinated axons in an individual fascicle. Osmium‐fixed nerves, counter‐stained with Masson's Trichrome. Scale bars: 500 µm on whole nerve images and 50 µm on higher magnification images [Colour figure can be viewed at wileyonlinelibrary.com]

4. DISCUSSION

The present study focuses on the WMS model and its applicability for researching BPI. Overall, this study demonstrates that the WMS brachial plexus closely resembles the human brachial plexus in comparison with other non‐primate vertebrate models (Hanna, 2016). The similarities can be appreciated through previous research with swine model post‐avulsion injury retaining more similarities to human models in terms of motor neuron death compared with small animal models (Koliatsos et al., 1994; Penas et al., 2009). The differences in physiological responses between these models may be due to species‐specific responses and/or age differences (Ali et al., 2016). The lack of clinically relevant therapies in rodent models despite their widespread use has resulted in more studies shifting their focus toward larger animal models. Miniture swine are comparable with humans from an anatomical, physiological, and pathophysiological perspective, making them a great model for BPI studies (Miranpuri et al., 2018).

Comparing the arrangement of the human brachial plexus to that of other common animal models, the human brachial plexus proves quite different. While the human brachial plexus is organized into key trunks, divisions, and cords, most animal models (pigs, cats, dogs, oxen, sheep, and goats) do not have this notable organization of the nerves (Septimus Sisson and Getty, 1986). While rabbits also do not have notable divisions and cords, they do have upper, middle, and lower trunks (Kollitz et al., 2020). Primates, most similar to humans, have three trunks, varying divisions, and three cords (Figueredo‐da‐Silva et al., 2021).

The clavicle, a major anatomical landmark in humans, has high variability within the animal kingdom both in regards to presence and to functionality (Table 2). de Souza et al. summarized this variability, identifying different classes of animals and the clavicle's role in each one's anatomy. They reported that the order Artiodactyla (including pigs, sheep, goats, and oxen) do not show evidence of clavicle formation. On the other hand, primates have fully developed clavicle bones. Lagomorpha (including rabbits) and Rodentia (including rats) have variable clavicle development based on family, and Carnivora (including cats and dogs) have vestigial or absent of clavicle bones (de Souza Junior et al., 2020).

TABLE 2.

Summary of variability in clavicle anatomy and trunks, divisions, and cords of the brachial plexus in common animal models

Clavicle Trunks Divisions Cords
Rat Varies x x x
Rabbit Varies √ x x
Cat √ (vestigial) x x x
Dog √ (vestigial) x x x
Sheep x x x x
Goat x x x x
Ox x x x x
Pig x x x x
Primate √ √ √ √
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In general, our anatomical results for the brachial plexus in WMS were consistent with previous findings in domestic pigs and wild boar (dos Santos, 2015; Septimus Sisson and Getty, 1986). The WMS suprascapular nerve originated from C5 and C6 (mainly C6) and the axillary nerve from C6 and C7 (mainly C7). The median, ulnar, and radial nerves originated from C7, C8, and T1 (mainly C8). The WMS musculocutanous nerve was a lot smaller and originated from C7 and C8 (Figures 1a and 2a).

Both the WMS median nerve and ulnar nerve had significantly smaller fascicles with significantly less axons that were significantly larger than human median and ulnar nerves (Figure 9). The more numerous myelinated axons in the human ulnar and median nerves are likely due to the demand of fine motor and sensory functions in the human hand. The larger axons in the WMS nerves may be explained by the larger muscles they innervate (more myofibers), which are needed for fight‐or‐flight responses (Lavelle et al., 2019).

Due to limited access, we were only able to obtain one suprascapular nerve, one radial nerve, and one axillary nerve from a fresh human cadaver. The WMS suprascapular, radial, and axillary nerves appeared to have many more fascicles that were significantly smaller than the corresponding human nerves (Figure 9). The WMS suprascapular and axillary nerves had more axons than the corresponding human nerves, and the axons were significantly larger (Figure 9). These large nerves with numerous large axons in the WMS are probably a function of their larger and stronger girdle muscles, possibly correlating with the swine's greater reliance on this region for mechanical support during movement.

The age discrepancy, underlying conditions, and low numbers of the fresh human cadavers are limitations of this study (Table 1). It is difficult to obtain fresh human samples that are uniform with regards to sex, weight, and age, and not complicated by differences in lifestyle, nutrition, diabetic neuropathy, occupation, etc. In this study, the swine were all of similar age and weight, whereas the humans varied in sex, age, and weight. Displaying the fascicle size and axon size for each individual specimen demonstrates some of these variations in the human subjects (Figure 9a,d). Interestingly, despite these differences, the current observations were overall consistent across all human subjects.

In terms of modeling the average human, the conventional pig breed would be approximately 3‐month‐old. This creates problems because pigs do not reach sexual maturity until 6 months of age and are rapidly growing. Moreover, the conventional breeds are not practical for long‐term studies, because the rapid rate of growth and remodeling would produce abnormal healing and poorly model nerve healing in human. The WMS attain an average human size at full maturity and maintain it for years.

5. CONCLUSIONS

Although there are differences between WMS brachial plexus and the human brachial plexus, they are close in size with similar composition and origin overall, making them a suitable animal model for BPI. Studying the anatomy and how it compares to humans was a crucial initial step in establishing the model. Future studies should be conducted to investigate the pathological mechanisms and clinical effects of BPI in WMS.

CONFLICT OF INTEREST

Dr. Shanmuganayagam is a co‐inventor of the Wisconsin Miniature Swine™ for Biomedical Research, licensing of which as a biological material is assigned to the Wisconsin Alumni Research Foundation (WARF) [WARF: P130271US01].

AUTHOR CONTRIBUTIONS

AH performed study concept and design, data acquisition including all animal dissections and human fixed cadaver dissection, data analysis and interpretation, drafting of the manuscript and critical revision. DH performed study concept and design, data acquisition, data analysis, and interpretation, statistical analysis, drafting of the manuscript, and critical revision. DTS performed study concept and design, data acquisition, drafting of the manuscript, and critical revision. SMS performed human fresh tissue harvest, data analysis, and interpretation. ML perfomed data acquisition, drafting of the manuscript, and critical revision. LW performed data acquisition, drafting of the manuscript, and critical revision BH performed data acquisition, drafting of the manuscript, and critical revision. BO performed data acquisition. DS (last) performed study concept and design, data acquisition, drafting of the manuscript, and critical revision. All authors read and approved the final manuscript.

ACKNOWLEDGMENTS

The authors are extremely grateful to the individuals who donated their bodies for the advancement of medicine. This article was made possible by the selfless gifts from these donors and/or their families. The authors would also like to thank the University of Wisconsin‐Madison, Department of Surgery, Histology Core Lab, Dr. Susan Thibeault PhD, CCC‐SLP, PI of the DOS Histology Core, along with certified Histotechnician, Sierra Raglin HTL (ASCP), and Lab Supervisor, Sara Dutton Sackett, PhD for their help with tissue processing.

Hanna, A.S. , Hellenbrand, D.J. , Schomberg, D.T. , Salamat, S.M. , Loh, M. , Wheeler, L. , et al (2022) Brachial plexus anatomy in the miniature swine as compared to human. Journal of Anatomy, 240, 172–181. 10.1111/joa.13525

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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