1932

Abstract

Insults in the prenatal and early postnatal period increase the risk for behavioral problems later in life. One hypothesis is that pre- and postnatal stressors influence structural and functional brain plasticity. Understanding the mechanisms is important, but progress has lagged because certain studies in human infants are impossible, while others are extremely difficult. Furthermore, results from popular rodent models are difficult to translate to human infants owing to the substantial differences in brain development and morphology. Because it overcomes some of these obstacles, the domestic piglet has emerged as an important model. Piglets have a gyrencephalic brain that develops similar to the human brain and that can be assessed in vivo by using clinical-grade neuroimaging instruments. Furthermore, owing to their precocial nature, piglets can be weaned at birth and used in behavioral testing paradigms to assess cognitive behavior at an early age. Thus, the domestic piglet represents an important translational model for investigating the neurodevelopmental consequences of early life insults.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-animal-022114-111049
2015-02-16
2024-12-05
Loading full text...

Full text loading...

/deliver/fulltext/animal/3/1/annurev-animal-022114-111049.html?itemId=/content/journals/10.1146/annurev-animal-022114-111049&mimeType=html&fmt=ahah

Literature Cited

  1. Rapp PR, Bachevalier J. 2008. Fundamental Neuroscience Squire L, Berg D, Bloom F, du Lac S, Ghosh A, Spitzer N. 1039–66 Burlington, MA: Elsevier [Google Scholar]
  2. Dobbing J, Sands J. 1979. Comparative aspects of the brain growth spurt. Early Hum. Dev. 3:79–83 [Google Scholar]
  3. Knickmeyer RC, Gouttard S, Kang C, Evans D, Wilber K et al. 2008. A structural MRI study of human brain development from birth to 2 years. J. Neurosci. 28:12176–82 [Google Scholar]
  4. Meyer U, Feldon J, Dammann O. 2011. Schizophrenia and autism: Both shared and disorder-specific pathogenesis via perinatal inflammation?. Pediatr. Res. 69:26R–33R [Google Scholar]
  5. Boksa P. 2010. Effects of prenatal infection on brain development and behavior: a review of findings from animal models. Brain Behav. Immun. 24:881–97 [Google Scholar]
  6. Harvey L, Boksa P. 2012. Prenatal and postnatal animal models of immune activation: relevance to a range of neurodevelopmental disorders. Dev. Neurobiol. 72:1335–48 [Google Scholar]
  7. Strauss RS. 2000. Adult functional outcome of those born small for gestational age: twenty-six-year follow-up of the 1970 British Birth Cohort. JAMA 283:625–32 [Google Scholar]
  8. Radlowski EC, Johnson RW. 2013. Perinatal iron deficiency and neurocognitive development. Front. Hum. Neurosci. 7:585 [Google Scholar]
  9. McEwen BS, Gianaros PJ. 2010. Central role of the brain in stress and adaptation: links to socioeconomic status, health, and disease. Ann. N.Y. Acad. Sci. 1186:190–222 [Google Scholar]
  10. Miller GE, Chen E, Fok AK, Walker H, Lim A et al. 2009. Low early-life social class leaves a biological residue manifested by decreased glucocorticoid and increased proinflammatory signaling. Proc. Natl. Acad. Sci. USA 106:14716–21 [Google Scholar]
  11. Dickerson JWT, Dobbing J. 1967. Prenatal and postnatal growth and development of the central nervous system of the pig. Proc. R. Soc. Lond. B Biol. Sci. 166:384–95 [Google Scholar]
  12. Thibault KL, Margulies SS. 1998. Age-dependent material properties of the porcine cerebrum: effect on pediatric inertial head injury criteria. J. Biomech. 31:1119–26 [Google Scholar]
  13. Ishizu K, Smith DF, Bender D, Danielsen E, Hansen SB et al. 2000. Positron emission tomography of radioligand binding in porcine striatum in vivo: haloperidol inhibition linked to endogenous ligand release. Synapse 38:87–101 [Google Scholar]
  14. Jakobsen S, Pedersen K, Smith DF, Jensen SB, Munk OL, Cumming P. 2006. Detection of α2-adrenergic receptors in brain of living pig with 11C-yohimbine. J. Nucl. Med. 47:2008–15 [Google Scholar]
  15. Fang M, Lorke DE, Li J, Gong X, Yew JC, Yew DT. 2005. Postnatal changes in functional activities of the pig's brain: a combined functional magnetic resonance imaging and immunohistochemical study. Neurosignals 14:222–33 [Google Scholar]
  16. Watanabe H, Andersen F, Simonsen CZ, Evans SM, Gjedde A, Cumming P. 2001. MR-based statistical atlas of the Göttingen minipig brain. Neuroimage 14:1089–96 [Google Scholar]
  17. Dilger RN, Johnson RW. 2008. Aging, microglial cell priming, and the discordant central inflammatory response to signals from the peripheral immune system. J. Leukoc. Biol. 84:932–39 [Google Scholar]
  18. Elmore MR, Dilger RN, Johnson RW. 2012. Place and direction learning in a spatial T-maze task by neonatal piglets. Anim. Cogn. 15:667–76 [Google Scholar]
  19. Patten BM. 1931. The Embryology of the Pig Philadelphia: P. Blakiston’s Son & Co [Google Scholar]
  20. Book SA, Bustad LK. 1974. The fetal and neonatal pig in biomedical research. J. Anim. Sci. 38:997–1002 [Google Scholar]
  21. van Straaten HWM, Peeters MCE, Hekking JWM, van der Lende T. 2000. Neurulation in the pig embryo. Anat. Embryol. 202:75–84 [Google Scholar]
  22. Nielsen KB, Sondergaard A, Johansen MG, Schauser K, Vejlsted M et al. 2010. Reelin expression during embryonic development of the pig brain. BMC Neurosci. 11:75 [Google Scholar]
  23. Pond WG, Boleman SL, Fiorotto ML, Ho H, Knabe DA et al. 2000. Perinatal ontogeny of brain growth in the domestic pig. Proc. Soc. Exp. Biol. Med. 223:102–8 [Google Scholar]
  24. Passingham RE. 1985. Rates of brain development in mammals including man. Brain Behav. Evol. 26:167–75 [Google Scholar]
  25. Conrad MS, Dilger RN, Johnson RW. 2012. Brain growth of the domestic pig (Sus scrofa) from 2 to 24 weeks of age: a longitudinal MRI study. Dev. Neurosci. 34:291–98 [Google Scholar]
  26. Jelsing J, Nielsen R, Olsen AK, Grand N, Hemmingsen R, Pakkenberg B. 2006. The postnatal development of neocortical neurons and glial cells in the Göttingen minipig and the domestic pig brain. J. Exp. Biol. 209:1454–62 [Google Scholar]
  27. Lind NM, Moustgaard A, Jelsing J, Vajta G, Cumming P, Hansen AK. 2007. The use of pigs in neuroscience: modeling brain disorders. Neurosci. Biobehav. Rev. 31:728–51 [Google Scholar]
  28. Niblock MM, Luce CJ, Belliveau RA, Paterson DS, Kelly ML et al. 2005. Comparative anatomical assessment of the piglet as a model for the developing human medullary serotonergic system. Brain Res. Rev. 50:169–83 [Google Scholar]
  29. Rosa-Neto P, Doudet DJ, Cumming P. 2004. Gradients of dopamine D1- and D2/3-binding sites in the basal ganglia of pig and monkey measured by PET. Neuroimage 22:1076–83 [Google Scholar]
  30. Larsen M, Bjarkam CR, Ostergaard K, West MJ, Sorensen JC. 2004. The anatomy of the porcine subthalamic nucleus evaluated with immunohistochemistry and design-based stereology. Anat. Embryol. 208:239–47 [Google Scholar]
  31. Agarwal RK, Chandna VK, Engelking LR, Lightbown K, Kumar MS. 1993. Distribution of catecholamines in the central nervous system of the pig. Brain Res. Bull. 32:285–91 [Google Scholar]
  32. Anderson NJ, Lupo PA, Nutt DJ, Hudson AL, Robinson ES. 2005. Characterisation of imidazoline I2 binding sites in pig brain. Eur. J. Pharmacol. 519:68–74 [Google Scholar]
  33. Marcilloux JC, Félix MB, Rampin O, Stoffels C, Ibazizen MT et al. 1993. Preliminary results of a magnetic resonance imaging (MRI) study of the pig brain placed in stereotaxic conditions. Neurosci. Lett. 156:113–16 [Google Scholar]
  34. Sørensen JC, Bjarkam CR, Danielsen EH, Simonsen CZ, Geneser FA. 2000. Oriented sectioning of irregular tissue blocks in relation to computerized scanning modalities: results from the domestic pig brain. J. Neurosci. Methods 104:93–98 [Google Scholar]
  35. Félix B, Léger ME, Albe-Fessard D, Marcilloux JC, Rampin O, Laplace JP. 1999. Stereotaxic atlas of the pig brain. Brain Res. Bull. 49:1–137 [Google Scholar]
  36. Rosa-Neto P, Gjedde A, Olsen AK, Jensen SB, Munk OL et al. 2004. MDMA-evoked changes in [11C]raclopride and [11C]NMSP binding in living pig brain. Synapse 53:222–33 [Google Scholar]
  37. Saikali S, Meurice P, Sauleau P, Eliat PA, Bellaud P et al. 2010. A three-dimensional digital segmented and deformable brain atlas of the domestic pig. J. Neurosci. Methods 192:102–9 [Google Scholar]
  38. Conrad MS, Dilger RN, Nickolls A, Johnson RW. 2012. Magnetic resonance imaging of the neonatal piglet brain. Pediatr. Res. 71:179–84 [Google Scholar]
  39. Winter JD, Dorner S, Lukovic J, Fisher JA, St Lawrence KS, Kassner A. 2011. Noninvasive MRI measures of microstructural and cerebrovascular changes during normal swine brain development. Pediatr. Res. 69:418–24 [Google Scholar]
  40. Alexander AL, Lee JE, Lazar M, Field AS. 2007. Diffusion tensor imaging of the brain. Neurotherapeutics 4:316–29 [Google Scholar]
  41. Thornton JS, Ordidge RJ, Penrice J, Cady EB, Amess PN et al. 1997. Anisotropic water diffusion in white and gray matter of the neonatal piglet brain before and after transient hypoxia-ischaemia. Magn. Reson. Imaging 15:433–40 [Google Scholar]
  42. Blüml S. 2013. Magnetic resonance spectroscopy: basics. MR Spectroscopy of Pediatric Brain Disorders Blüml S, Panigrahy A. 11–23 New York: Springer [Google Scholar]
  43. Smith DH, Cecil KM, Meaney DF, Chen XH, McIntosh TK et al. 1998. Magnetic resonance spectroscopy of diffuse brain trauma in the pig. J. Neurotrauma 15:665–74 [Google Scholar]
  44. Munkeby BH, De Lange C, Emblem KE, Bjørnerud A, Kro GA et al. 2008. A piglet model for detection of hypoxic-ischemic brain injury with magnetic resonance imaging. Acta Radiol. 49:1049–57 [Google Scholar]
  45. Fang M, Li J, Rudd JA, Wai SM, Yew JC, Yew DT. 2006. fMRI mapping of cortical centers following visual stimulation in postnatal pigs of different ages. Life Sci. 78:1197–201 [Google Scholar]
  46. Vallet JL, Miles JR, Freking BA. 2009. Development of the pig placenta. Soc. Reprod. Fertil. Suppl. 66:265–79 [Google Scholar]
  47. Workman AD, Charvet CJ, Clancy B, Darlington RB, Finlay BL. 2013. Modeling transformations of neurodevelopmental sequences across mammalian species. J. Neurosci. 33:7368–83 [Google Scholar]
  48. Gieling ET, Nordquist RE, van der Staay FJ. 2011. Assessing learning and memory in pigs. Anim. Cogn. 14:151–73 [Google Scholar]
  49. Kornum BR, Knudsen GM. 2011. Cognitive testing of pigs (Sus scrofa) in translational biobehavioral research. Neurosci. Biobehav. Rev. 35:437–51 [Google Scholar]
  50. Dilger RN, Johnson RW. 2010. Behavioral assessment of cognitive function using a translational neonatal piglet model. Brain Behav. Immun. 24:1156–65 [Google Scholar]
  51. Gieling ET, Antonides A, Fink-Gremmels J, ter Haar K, Kuller WI et al. 2014. Chronic allopurinol treatment during the last trimester of pregnancy in sows: effects on low and normal birth weight offspring. PLOS ONE 9:e86396 [Google Scholar]
  52. Gieling ET, Park SY, Nordquist RE, van der Staay FJ. 2012. Cognitive performance of low- and normal-birth-weight piglets in a spatial hole-board discrimination task. Pediatr. Res. 71:7176 [Google Scholar]
  53. van der Staay FJ, Gieling ET, Pinzón NE, Nordquist RE, Ohl F. 2012. The appetitively motivated “cognitive” holeboard: a family of complex spatial discrimination tasks for assessing learning and memory. Neurosci. Biobehav. Rev. 36:379–403 [Google Scholar]
  54. Stolba A, Woodgush DGM. 1989. The behavior of pigs in a semi-natural environment. Anim. Prod. 48:419–25 [Google Scholar]
  55. Elmore MR, Burton MD, Conrad MS, Rytych JL, Van Alstine WG, Johnson RW. 2014. Respiratory viral infection in neonatal piglets causes marked microglia activation in the hippocampus and deficits in spatial learning. J. Neurosci. 34:2120–29 [Google Scholar]
  56. Jurgens HA, Amancherla K, Johnson RW. 2012. Influenza infection induces neuroinflammation, alters hippocampal neuron morphology, and impairs cognition in adult mice. J. Neurosci. 32:3958–68 [Google Scholar]
  57. Rytych JL, Elmore MR, Burton MD, Conrad MS, Donovan SM et al. 2012. Early life iron deficiency impairs spatial cognition in neonatal piglets. J. Nutr. 142:2050–56 [Google Scholar]
  58. Wang B, Yu B, Karim M, Hu H, Sun Y et al. 2007. Dietary sialic acid supplementation improves learning and memory in piglets. Am. J. Clin. Nutr. 85:561–69 [Google Scholar]
  59. Buchanan JB, Sparkman NL, Chen J, Johnson RW. 2008. Cognitive and neuroinflammatory consequences of mild repeated stress are exacerbated in aged mice. Psychoneuroendocrinology 33:755–65 [Google Scholar]
  60. Cornwell BR, Johnson LL, Holroyd T, Carver FW, Grillon C. 2008. Human hippocampal and parahippocampal theta during goal-directed spatial navigation predicts performance on a virtual Morris water maze. J. Neurosci. 28:5983–90 [Google Scholar]
  61. Jarrard LE. 1995. What does the hippocampus really do?. Behav. Brain Res. 71:1–10 [Google Scholar]
  62. Fitz NF, Gibbs RB, Johnson DA. 2008. Selective lesion of septal cholinergic neurons in rats impairs acquisition of a delayed matching to position T-maze task by delaying the shift from a response to a place strategy. Brain Res. Bull. 77:356–60 [Google Scholar]
  63. Stringer KG, Martin GM, Skinner DM. 2005. The effects of hippocampal lesions on response, direction, and place learning in rats. Behav. Neurosci. 119:946–52 [Google Scholar]
  64. Tolman EC, Ritchie BF, Kalish D. 1946. Studies in spatial learning; place learning versus response learning. J. Exp. Psychol. 36:221–29 [Google Scholar]
  65. Walsh SJ, Harley CW, Corbett D, Skinner DM, Martin GM. 2008. CA1 ischemic injury does not affect the ability of Mongolian gerbils to solve response, direction, or place problems. Brain Res. 1187:194–200 [Google Scholar]
  66. Zurkovsky L, Brown SL, Korol DL. 2006. Estrogen modulates place learning through estrogen receptors in the hippocampus. Neurobiol. Learn. Mem. 86:336–43 [Google Scholar]
  67. Decker MW, McGaugh JL. 1991. The role of interactions between the cholinergic system and other neuromodulatory systems in learning and memory. Synapse 7:151–68 [Google Scholar]
  68. Ebert U, Kirch W. 1998. Scopolamine model of dementia: electroencephalogram findings and cognitive performance. Eur. J. Clin. Investig. 28:944–49 [Google Scholar]
  69. Mesulam MM, Mufson EJ, Levey AI, Wainer BH. 1983. Cholinergic innervation of cortex by the basal forebrain: cytochemistry and cortical connections of the septal area, diagonal band nuclei, nucleus basalis (substantia innominata), and hypothalamus in the rhesus monkey. J. Comp. Neurol. 214:170–97 [Google Scholar]
  70. Nielsen TR, Kornum BR, Moustgaard A, Gade A, Lind NM, Knudsen GM. 2009. A novel spatial delayed non-match to sample (DNMS) task in the Göttingen minipig. Behav. Brain Res. 196:93–98 [Google Scholar]
  71. Roohey T, Raju TN, Moustogiannis AN. 1997. Animal models for the study of perinatal hypoxic-ischemic encephalopathy: a critical analysis. Early Hum. Dev. 47:115–46 [Google Scholar]
  72. Raju TN. 1992. Some animal models for the study of perinatal asphyxia. Biol. Neonate 62:202–14 [Google Scholar]
  73. Haaland K, Loberg EM, Steen PA, Thoresen M. 1997. Posthypoxic hypothermia in newborn piglets. Pediatr. Res. 41:505–12 [Google Scholar]
  74. Björkman ST, Foster KA, O'Driscoll SM, Healy GN, Lingwood BE et al. 2006. Hypoxic/ischemic models in newborn piglet: comparison of constant FiO2 versus variable FiO2 delivery. Brain Res. 1100:110–17 [Google Scholar]
  75. Agnew DM, Koehler RC, Guerguerian AM, Shaffner DH, Traystman RJ et al. 2003. Hypothermia for 24 hours after asphyxic cardiac arrest in piglets provides striatal neuroprotection that is sustained 10 days after rewarming. Pediatr. Res. 54:253–62 [Google Scholar]
  76. Alonso-Spilsbury M, Mota-Rojas D, Villanueva-García D, Martínez-Burnes J, Orozco H et al. 2005. Perinatal asphyxia pathophysiology in pig and human: a review. Anim. Reprod. Sci. 90:1–30 [Google Scholar]
  77. LeBlanc MH, Vig V, Smith B, Parker CC, Evans OB, Smith EE. 1991. MK-801 does not protect against hypoxic-ischemic brain injury in piglets. Stroke 22:1270–75 [Google Scholar]
  78. Barkovich AJ, Miller SP, Bartha A, Newton N, Hamrick SE et al. 2006. MR imaging, MR spectroscopy, and diffusion tensor imaging of sequential studies in neonates with encephalopathy. Am. J. Neuroradiol. 27:533–47 [Google Scholar]
  79. Vial F, Serriere S, Barantin L, Montharu J, Nadal-Desbarats L et al. 2004. A newborn piglet study of moderate hypoxic-ischemic brain injury by 1H-MRS and MRI. Magn. Reson. Imaging 22:457–65 [Google Scholar]
  80. Cheng Y, Liu GR, Guan JT, Guo YL, Li YK, Wu RH. 2005. Early diffusion weighted imaging and expression of heat shock protein 70 in newborn pigs with hypoxic ischaemic encephalopathy. Postgrad. Med. J. 81:589–93 [Google Scholar]
  81. Munkeby BH, Lyng K, Froen JF, Winther-Larssen EH, Rosland JH et al. 2004. Morphological and hemodynamic magnetic resonance assessment of early neonatal brain injury in a piglet model. J. Magn. Reson. Imaging 20:8–15 [Google Scholar]
  82. Higgins RD, Raju T, Edwards AD, Azzopardi DV, Bose CL et al. 2011. Hypothermia and other treatment options for neonatal encephalopathy: an executive summary of the Eunice Kennedy Shriver NICHD workshop. J. Pediatr. 159:851–58.e1 [Google Scholar]
  83. Thoresen M, Haaland K, Loberg EM, Whitelaw A, Apricena F et al. 1996. A piglet survival model of posthypoxic encephalopathy. Pediatr. Res. 40:738–48 [Google Scholar]
  84. Thoresen M, Tooley J, Liu X, Jary S, Fleming P et al. 2013. Time is brain: Starting therapeutic hypothermia within three hours after birth improves motor outcome in asphyxiated newborns. Neonatology 104:228–33 [Google Scholar]
  85. Tagin MA, Woolcott CG, Vincer MJ, Whyte RK, Stinson DA. 2012. Hypothermia for neonatal hypoxic ischemic encephalopathy: an updated systematic review and meta-analysis. Arch. Pediatr. Adolesc. Med. 166:558–66 [Google Scholar]
  86. Shankaran S, Pappas A, McDonald SA, Vohr BR, Hintz SR et al. 2012. Childhood outcomes after hypothermia for neonatal encephalopathy. N. Engl. J. Med. 366:2085–92 [Google Scholar]
  87. Perlman JM, Wyllie J, Kattwinkel J, Atkins DL, Chameides L et al. 2010.N eonatal resuscitation: 2010 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations. Circulation 122:S516–38 [Google Scholar]
  88. Zanelli SA, Naylor M, Dobbins N, Quigg M, Goodkin HP et al. 2008. Implementation of a ‘Hypothermia for HIE' program: 2-year experience in a single NICU. J. Perinatol. 28:171–75 [Google Scholar]
  89. Subcomm. Swine Nutr., Comm. Anim. Nutr., Natl. Res. Counc 1998. Nutrient Requirements of Swine: 10th. Revised Edition Washington, DC: Natl. Acad. Press [Google Scholar]
  90. Miller ER, Ullrey DE. 1987. The pig as a model for human nutrition. Annu. Rev. Nutr. 7:361–82 [Google Scholar]
  91. McLean E, Cogswell M, Egli I, Wojdyla D, de Benoist B. 2009. Worldwide prevalence of anaemia, WHO Vitamin and Mineral Nutrition Information System, 1993–2005. Public Health Nutr. 12:444–54 [Google Scholar]
  92. Natl. Res. Counc 1998. Nutrient Requirements of Swine Washington, DC: Natl. Acad. Press [Google Scholar]
  93. Johnson MH. 2001. Functional brain development in humans. Nat. Rev. Neurosci. 2:475–83 [Google Scholar]
  94. Aarnoudse-Moens CSH, Weisglas-Kuperus N, van Goudoever JB, Oosterlaan J. 2009. Meta-analysis of neurobehavioral outcomes in very preterm and/or very low birth weight children. Pediatrics 124:717–28 [Google Scholar]
  95. Gutbrod T, Wolke D, Soehne B, Ohrt B, Riegel K. 2000. Effects of gestation and birth weight on the growth and development of very low birthweight small for gestational age infants: a matched group comparison. Arch. Dis. Child. Fetal Natal 82:F208–14 [Google Scholar]
  96. Benton D. 2010. The influence of dietary status on the cognitive performance of children. Mol. Nutr. Food Res. 54:457–70 [Google Scholar]
  97. Larroque B, Bertrais S, Czernichow P, Léger J. 2001. School difficulties in 20-year-olds who were born small for gestational age at term in a regional cohort study. Pediatrics 108:111–15 [Google Scholar]
  98. Mathews T, MacDorman MF. 2010. Infant mortality statistics from the 2006 period linked birth/infant death data set. Natl. Vital Stat. Rep. 58:1–31 [Google Scholar]
  99. Baker-Henningham H, Hamadani JD, Huda SN, Grantham-McGregor SM. 2009. Undernourished children have different temperaments than better-nourished children in rural Bangladesh. J. Nutr. 139:1765–71 [Google Scholar]
  100. Walker SP, Chang SM, Powell CA, Simonoff E, Grantham-McGregor SM. 2007. Early childhood stunting is associated with poor psychological functioning in late adolescence and effects are reduced by psychosocial stimulation. J. Nutr. 137:2464–69 [Google Scholar]
  101. Radlowski EC, Conrad MS, Lezmi S, Dilger RN, Sutton B et al. 2014. A neonatal piglet model for investigating brain and cognitive development in small for gestational age human infants. PLOS ONE 9:e91951 [Google Scholar]
  102. Skranes J, Vangberg TR, Kulseng S, Indredavik MS, Evensen KA et al. 2007. Clinical findings and white matter abnormalities seen on diffusion tensor imaging in adolescents with very low birth weight. Brain 130:654–66 [Google Scholar]
  103. Lepomaki V, Matomaki J, Lapinleimu H, Lehtonen L, Haataja L et al. 2013. Effect of antenatal growth on brain white matter maturation in preterm infants at term using tract-based spatial statistics. Pediatr. Radiol. 43:80–85 [Google Scholar]
  104. Meurens F, Summerfield A, Nauwynck H, Saif L, Gerdts V. 2012. The pig: a model for human infectious diseases. Trends Microbiol. 20:50–57 [Google Scholar]
  105. Freeman T, Ivens A, Baillie J, Beraldi D, Barnett M et al. 2012. A gene expression atlas of the domestic pig. BMC Biol. 10:1–22 [Google Scholar]
  106. Dawson HD. 2011. A comparative assessment of the pig, mouse, and human genomes: structural and functional analysis of genes involved in immunity and inflammation. The Minipig in Biomedical Research McAnulty PA, Dayan AD, Ganderup NC, Hastings KI. 323–42 Boca Raton, FL: CRC Press [Google Scholar]
  107. Pampusch MS, Bennaars AM, Harsch S, Murtaugh MP. 1998. Inducible nitric oxide synthase expression in porcine immune cells. Vet. Immunol. Immunopathol. 61:279–89 [Google Scholar]
  108. Svedman P, Ljungh A, Rausing A, Banck G, Sanden G et al. 1989. Staphylococcal wound infection in the pig: part I. Course. Ann. Plast. Surg. 23:212–18 [Google Scholar]
  109. Jensen HE, Nielsen OL, Agerholm JS, Iburg T, Johansen LK et al. 2010. A non-traumatic Staphylococcus aureus osteomyelitis model in pigs. In Vivo 24:257–64 [Google Scholar]
  110. Luna CM, Sibila O, Agusti C, Torres A. 2009. Animal models of ventilator-associated pneumonia. Eur. Respir. J. 33:182–88 [Google Scholar]
  111. Elahi S, Buchanan RM, Babiuk LA, Gerdts V. 2006. Maternal immunity provides protection against pertussis in newborn piglets. Infect. Immun. 74:2619–27 [Google Scholar]
  112. Saif LJ, Ward LA, Yuan L, Rosen BI, To TL. 1996. The gnotobiotic piglet as a model for studies of disease pathogenesis and immunity to human rotaviruses. Arch. Virol. Suppl. 12:153–61 [Google Scholar]
  113. Duan X, Nauwynck HJ, Pensaert MB. 1997. Virus quantification and identification of cellular targets in the lungs and lymphoid tissues of pigs at different time intervals after inoculation with porcine reproductive and respiratory syndrome virus (PRRSV). Vet. Microbiol. 56:9–19 [Google Scholar]
  114. Rossow KD, Shivers JL, Yeske PE, Polson DD, Rowland RRR et al. 1999. Porcine reproductive and respiratory syndrome virus infection in neonatal pigs characterised by marked neurovirulence. Vet. Rec. 144:444–48 [Google Scholar]
  115. Miguel JC, Chen J, Van Alstine WG, Johnson RW. 2010. Expression of inflammatory cytokines and Toll-like receptors in the brain and respiratory tract of pigs infected with porcine reproductive and respiratory syndrome virus. Vet. Immunol. Immunopathol. 135:314–19 [Google Scholar]
/content/journals/10.1146/annurev-animal-022114-111049
Loading
/content/journals/10.1146/annurev-animal-022114-111049
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error