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Electroporation-Mediated Delivery of Genes in Rodent Models of Lung Contusion

  • David Machado-Aranda
  • Krishnan Raghavendran
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1121)

Abstract

Several of the biological processes involved in the pathogenesis of acute lung injury and acute respiratory distress syndrome after lung contusion are regulated at a genetic and epigenetic level. Thus, strategies to manipulate gene expression in this context are highly desirable not only to elucidate the mechanisms involved but also to look for potential therapies. In the present chapter, we describe mouse and rat models of inducing blunt thoracic injury followed by electroporation-mediated gene delivery to the lung. Electroporation is a highly efficient and easily reproducible technique that allows circumvention of several of lung gene delivery challenges and safety issues present with other forms of lung gene therapy.

Key words

Lung contusion Acute lung injury Acute respiratory distress syndrome Electroporation 

References

  1. 1.
    Kollmorgen DR, Murray KA, Sullivan JJ, Mone MC, Barton RG (1994) Predictors of mortality in pulmonary contusion. Am J Surg 168:659–663PubMedCrossRefGoogle Scholar
  2. 2.
    Miller PR, Croce MA, Kilgo PD, Scott J, Fabian TC (2002) Acute respiratory distress syndrome in blunt trauma: identification of independent risk factors. Am Surg 68:845–850PubMedGoogle Scholar
  3. 3.
    Wu J, Sheng L, Ma Y et al (2008) The analysis of risk factors of impacting mortality rate in severe multiple trauma patients with posttraumatic acute respiratory distress syndrome. Am J Emerg Med 26:419–424PubMedCrossRefGoogle Scholar
  4. 4.
    ARDS_Network (2000) Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The acute respiratory distress syndrome network. N Engl J Med 342:1301–1308CrossRefGoogle Scholar
  5. 5.
    Network ARDS (2000) Ketoconazole for early treatment of acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. The ards network. Jama 283:1995–2002CrossRefGoogle Scholar
  6. 6.
    Blank R, Napolitano LM (2011) Epidemiology of ards and ali. Crit Care Clin 27:439–458PubMedCrossRefGoogle Scholar
  7. 7.
    Bone RC, Fisher CJ Jr, Clemmer TP, Slotman GJ, Metz CA (1987) Early methylprednisolone treatment for septic syndrome and the adult respiratory distress syndrome. Chest 92:1032–1036PubMedCrossRefGoogle Scholar
  8. 8.
    Brower RG, Lanken PN, MacIntyre N et al (2004) Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. N Engl J Med 351:327–336PubMedCrossRefGoogle Scholar
  9. 9.
    Gallagher DC, Parikh SM, Balonov K et al (2008) Circulating angiopoietin 2 correlates with mortality in a surgical population with acute lung injury/adult respiratory distress syndrome. Shock 29:656–661PubMedGoogle Scholar
  10. 10.
    Matthay MA, Brower RG, Carson S et al (2011) Randomized, placebo-controlled clinical trial of an aerosolized beta-agonist for treatment of acute lung injury. Am J Respir Crit Care Med 184:561–568PubMedCrossRefGoogle Scholar
  11. 11.
    Matthay MA, Zimmerman GA, Esmon C et al (2003) Future research directions in acute lung injury: summary of a national heart, lung, and blood institute working group. Am J Respir Crit Care Med 167:1027–1035PubMedCrossRefGoogle Scholar
  12. 12.
    Machado-Aranda DA, Suresh MV, Yu B, Raghavendran K (2012) Electroporation-mediated in vivo gene delivery of the na+/k+-atpase pump reduced lung injury in a mouse model of lung contusion. J Trauma Acute Care Surg 72:32–39PubMedCentralPubMedGoogle Scholar
  13. 13.
    Raghavendran K, Davidson BA, Helinski JD et al (2005) A rat model for isolated bilateral lung contusion from blunt chest trauma. Anesth Analg 101:1482–1489PubMedCrossRefGoogle Scholar
  14. 14.
    Raghavendran KDB, Helinski JD, Marschke CM, Woytash JA, Notter RH, Knight PR (2004) A new rat model for isolated bilateral lung contusion-reversal of hypoxia by 24 hours. Crit Care Med. Poster presentation at Society for Critical Care Medicine Google Scholar
  15. 15.
    Suresh MV, Yu B, Machado-Aranda D et al (2012) Role of macrophage chemoattractant protein 1 in acute inflammation following lung contusion. Am. J. Respir. Cell Mol, BiolGoogle Scholar
  16. 16.
    Hoth JJ, Hudson WP, Brownlee NA et al (2007) Toll-like receptor 2 participates in the response to lung injury in a murine model of pulmonary contusion. Shock 28:447–452PubMedCrossRefGoogle Scholar
  17. 17.
    Hoth JJ, Stitzel JD, Gayzik FS et al (2006) The pathogenesis of pulmonary contusion: an open chest model in the rat. J Trauma 61:32–44, discussion 44–35PubMedCrossRefGoogle Scholar
  18. 18.
    Hoth JJ, Wells JD, Hiltbold EM, McCall CE, Yoza BK (2011) Mechanism of neutrophil recruitment to the lung after pulmonary contusion. Shock 15:15Google Scholar
  19. 19.
    Bauer HC, Traweger A, Zweimueller-Mayer J et al (2011) New aspects of the molecular constituents of tissue barriers. J Neural Transm 118:7–21PubMedCrossRefGoogle Scholar
  20. 20.
    Lin X, Dean DA (2011) Gene therapy for ali/ards. Crit Care Clin 27:705–718PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Howrylak JA, Dolinay T, Lucht L et al (2009) Discovery of the gene signature for acute lung injury in patients with sepsis. Physiol Genomics 37:133–139PubMedCrossRefGoogle Scholar
  22. 22.
    Dean DA, Machado-Aranda D, Blair-Parks K, Yeldandi AV, Young JL (2003) Electroporation as a method for high-level nonviral gene transfer to the lung. Gene Ther 10:1608–1615PubMedCrossRefGoogle Scholar
  23. 23.
    Machado-Aranda D, Adir Y, Young JL et al (2005) Gene transfer of the na+, k+-atpase beta1 subunit using electroporation increases lung liquid clearance. Am J Respir Crit Care Med 171:204–211PubMedCrossRefGoogle Scholar
  24. 24.
    Mutlu GM, Machado-Aranda D, Norton JE et al (2007) Electroporation-mediated gene transfer of the na+, k+-atpase rescues endotoxin-induced lung injury. Am J Respir Crit Care Med 176:582–590PubMedCrossRefGoogle Scholar
  25. 25.
    Gatson JW, Liu MM, Abdelfattah K et al (2013) Resveratrol decreases inflammation in the brain of mice with mild traumatic brain injury. J Trauma Acute Care Surg 74:470–475PubMedCrossRefGoogle Scholar
  26. 26.
    Mouzon B, Chaytow H, Crynen G et al (2012) Repetitive mild traumatic brain injury in a mouse model produces learning and memory deficits accompanied by histological changes. J Neurotrauma 29:2761–2773PubMedCrossRefGoogle Scholar
  27. 27.
    Sangiorgi S, De Benedictis A, Protasoni M et al (2013) Early-stage microvascular alterations of a new model of controlled cortical traumatic brain injury: 3d morphological analysis using scanning electron microscopy and corrosion casting. J Neurosurg 118:763–774PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • David Machado-Aranda
    • 1
  • Krishnan Raghavendran
    • 1
  1. 1.Division of Acute Care Surgery, Department of SurgeryUniversity of MichiganAnn ArborUSA

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