Abstract
Small bowel transplantation (SBT) is associated with poorly understood enteric dysfunction. The study of SBT in mice is hindered by the technical difficulty of orthotopic SBT in the mouse. Our aim was to develop an easy preparation of extrinsic denervation of the entire jejunoileum in mice as a model of orthotopic SBT. All neurolymphatic tissues accompanying the superior mesenteric artery (SMA) and vein (SMV) were ligated just distal to the middle colic vessels. The SMA and SMV were then stripped of investing adventitia, and the mesentery to jejunum and colon were transected radially. Jejunum and colon were not transected and reanastomosed. To confirm extrinsic denervation 1, 3, and 6 months later, segments of small bowel were stained for protein gene product 9.5 (PGP9.5) and tyrosine hydroxylase (TH). Tyrosine hydroxylase immunoreactive intensity was then quantified using a semiquantitative analysis. Immunohistochemical fluorescence showed persistence of PGP9.5 immunoreactivity confirming enteric nerves in jejunoileum; however, there was no TH immunoreactivity in jejunoileum in denervated mice despite the expected preservation of TH immunoreactivity in the still-innervated duodenum at 1 month. At 3 months, sparse immunoreactivity for TH was present, and by 6 months, reinnervation of TH-containing nerves appeared similar to controls. Quantification of intensity at each time-point further confirmed this trend. This technique in the mouse accomplishes a complete extrinsic denervation of jejunoileum early postoperatively (1 and 3 months); reinnervation occurs by 6 months. This is an easily learned murine model of orthotopic SBT.
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References
Todo S, Reyes J, Furukawa H, Abu-Elmagd K, Lee RG, Tzakis A, Rao AS, et al. Outcome analysis of 71 clinical intestinal transplantations. Ann Surg 1995;222:270–280; discussion 280–272.
Thompson JS, Rose SG, Spanta AD, Quigley EM. The long-term effect of jejunoileal autotransplantation on intestinal function. Surgery 1992;111:62–68.
Zarroug AE, Libsch KD, Houghton SG, Duenes JA, Sarr MG. Postprandial augmentation of absorption of water and electrolytes in jejunum is neurally modulated: implications for segmental small bowel transplantation. J Gastrointest Surg 2006;10:586–592.
Oishi AJ, Sarr MG. Intestinal transplantation: effects on ileal enteric absorptive physiology. Surgery 1995;117:545–553.
Sarr MG, Hakim NS. Enteric Physiology of the Transplanted Intestine. Austin: R.G. Landes Company, 1994.
Sarr MG, Duenes JA, Tanaka M. A model of jejunoileal in vivo neural isolation of the entire jejunoileum: transplantation and the effects on intestinal motility. J Surg Res 1989;47:266–272.
Houghton SG, Nicholson VD, Sarr MG. In vivo complete neural isolation of the rat jejunoileum: a simple model to study denervation sequelae of intestinal transplantation. J Surg Res 2006;131:53–57.
Sugitani A, Reynolds JC, Todo S. Immunohistochemical study of enteric nervous system after small bowel transplantation in humans. Dig Dis Sci 1994;39:2448–2456.
Hirose R, Taguchi T, Hirata Y, Yamada T, Nada O, Suita S. Immunohistochemical demonstration of enteric nervous distribution after syngeneic small bowel transplantation in rats. Surgery 1995;117:560–569.
Squiers EC, Kelley Se, West JC. Small bowel transplantation in the mouse: development of a model. Microsurgery 1992;13:345–347.
Zhong R, Zhang Z, Quan D, Duff J, Stiller C, Grant D. Development of a mouse intestinal transplantation model. Microsurgery 1993;14:141–145.
Liu J, Fishbein TM, Bromberg JS, Boros P. Orthotopic small bowel transplantation in mice. Transplantation 2005;79:973–976.
Kiyochi H, Ono A, Yamamoto N, Ohnishi K, Shimahara Y, Kobayashi N. Extrinsic sympathetic reinnervation after intestinal transplantation in rats. Transplantation 1995;59:328–333.
Hill CE, Hirst GD, Ngu MC, van Helden DF. Sympathetic postganglionic reinnervation of mesenteric arteries and enteric neurones of the ileum of the rat. J Auton Nerv Syst 1985;14:317–334.
Furness JB, Costa M. The adrenergic innervation of the gastrointestinal tract. Ergeb Physiol 1974;69:2–51.
Li ZS, Pham TD, Tamir H, Clen JJ, Gershon MD. Enteric dopaminergic neurons: definition, developmental lineage, and effects of extrinsic denervation. J Neurosci 2004;24:1330–1339.
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Fatima, J., Houghton, S.G. & Sarr, M.G. Development of a Simple Model of Extrinsic Denervation of the Small Bowel in Mouse. J Gastrointest Surg 11, 1052–1056 (2007). https://doi.org/10.1007/s11605-007-0185-0
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DOI: https://doi.org/10.1007/s11605-007-0185-0