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Published in:

01-02-2012

Effect of Donor JNK Signal Transduction Inhibition on Transplant Outcome in Brain Dead Rat Model

Authors: Lu Chen, Danfeng Xu, Yi Gao, Xingang Cui, Zunguo Du, Qiang Ding, Xiang Wang

Published in: Inflammation | Issue 1/2012

Abstract

Renal grafts from brain-dead donors compared to living donors have a significantly shortened survival time due to heightened renal immunogenicity. The influence of pretreatment with a JNK signal transduction inhibitor on ischemia–reperfusion injury was examined in a renal transplant model using donors from a standardized rat model of brain death. Donors were treated immediately after induction of brain death with a JNK signal transduction inhibitor or saline. Kidney grafts from experimental group and control groups (saline-treated brain dead or living donor grafts) were examined serially up to 7 days post transplantation by morphology, immmunohistology, and real-time PCR. JNK inhibition reduced the intensity of ischemia–reperfusion injury and acute rejection compared to saline treated donors. Likewise, cellular infiltration, mRNA transcription of some representative proinflammatory mediators and MHC-II molecules in the grafts were diminished in the JNK-inhibited donors compared to saline controls. Lewis rats transplanted with kidneys from JNK inhibited, brain-dead BN donors survived significantly longer than rats transplanted with saline treated brain-dead donors. The JNK inhibitor pretreatment of brain dead rats improved donor kidney quality, and improved graft survival.

US Department of Health and Human Services. 2004 Annual Report of the US Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients: Transplant Data 1994–2003, 2005.

Terasaki, P.I., J.M. Cecka, D.W. Gjertson, et al. 1995. High survival rates of kidney transplants from spousal and living unrelated donors. New Engl J Med 333: 333.PubMedCrossRef

Herijgers, P., V. Leunens, T.B. Tjandra-Maga, et al. 1996. Changes in organ perfusion after brain death in the rat and its relation to circulating catecholamines. Transplantation 62: 330.PubMedCrossRef

van der Hoeven, J.A., G. Molema, G.J. Ter Horst, et al. 2003. Relationship between duration of brain death and hemodynamic (in) stability on progressive dysfunction and increased immunologic activation of donor kidneys. Kidney International 64: 1874.PubMedCrossRef

van den Eijnden, M.M., H.G. Leuvenink, P.J. Ottens, et al. 2003. Effect of brain death and non-heart-beating kidney donation on renal function and injury: an assessment in the isolated perfused rat kidney. Experimental and Clinical Transplantation 1: 85.PubMed

Nijboer, W.N., T.A. Schuurs, J.A.B. van der Hoeven, et al. 2005. Effect of brain death on stress and inflammatory response in the human donor kidneys. Transplantation Proceedings 37: 367.PubMedCrossRef

Nijboer, W.N., T.A. Schuurs, J.A. van der Hoeven, et al. 2004. Effect of brain death on gene expression and tissue activation in human donor kidneys. Transplantation 78: 978.PubMedCrossRef

Bennett, B.L., D.T. Sasaki, B.W. Murray, et al. 2001. SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase. PNAS 98: 13681.PubMedCrossRef

Milano, G., S. Morel, C. Bonny, et al. 2007. A peptide inhibitor of c-Jun NH2-terminal kinase reduces myocardial ischemia-reperfusion injury and infarct size in vivo. American Journal of Physiology. Heart and Circulatory Physiology 292: 1828.CrossRef

10.

Noguchi, H., S. Matsumoto, N. Kobayashi, et al. 2008. Effect of JNK inhibitor during islet isolation and transplantation. Transplantation Proceedings 40: 379.PubMedCrossRef

11.

Tabata, A., M. Morikawa, M. Miyajima, et al. 2007. Suppression of alloreactivity and allograft rejection by SP600125, a small molecule inhibitor of c-Jun N-terminal kinase. Transplantation 83: 1358.PubMedCrossRef

12.

Schumacher, M., B.N. Van Vliet, and P. Ferrari. 2003. Kidney transplantation in rats: an appraisal of surgical techniques and outcome. Microsurgery 23: 387.PubMedCrossRef

13.

Lee, S. 1967. An improved technique of renal transplantation in the rat. Surgery 61: 771.PubMed

14.

Pahlavan, P.S., C. Smallegange, et al. 2006. Kidney transplantation procedures in rats: assessments, complications, and management. Microsurgery 26: 404.PubMedCrossRef

15.

Pietsch, A.P., P.C. Nett, E. Klar, et al. 2005. A new modified technique of ureteroureterostomy in rat kidney transplantation. Transplantation Proceedings 37: 189.PubMedCrossRef

16.

Karatzas, T., S. Santiago, T. Xanthos, et al. 2007. An easy and safe model of kidney transplantation in rats. Microsurgery 27: 668.PubMedCrossRef

17.

Martins, P.N. 2006. Kidney transplantation in the rat: A modified technique using hydrodissection. Microsurgery 26: 543.PubMedCrossRef

18.

Pratschke, J., P. Neuhaus, and S.G. Tullius. 2005. What can be learned from brain death models? Transplant International 18: 15.PubMedCrossRef

19.

Shivalkar, B., J. Van Loon, W. Wieland, et al. 1993. Variable effects of explosive or gradual increase of intracranial pressure on myocardial structure and function. Circulation 87: 230.PubMed

20.

Pratschke, J., M.J. Wilhelm, M. Kusaka, et al. 2000. A model of gradual onset brain death for transplant-associated studies in rats. Transplantation 69: 427.PubMedCrossRef

21.

Kotsch, K., M. Francuski, A. Pascher, et al. 2006. Improved long-term graft survival after HO-1 induction in brain-dead donors. American Journal of Transplantation 6: 477.PubMedCrossRef

22.

Solez, K., H. Benediktsson, T. Cavallo, et al. 1996. Report of the Third Banff Conference on Allograft Pathology (July 20–24, 1995) on classification and lesion scoring in renal allograft pathology. Transplantation Proceedings 28: 441.PubMed

23.

Gasser, M., A.M. Waaga-Gasser, M.W. Grimm, M.R. Grimm, et al. 2005. Selectin blockade plus therapy with low-dose sirolimus and cyclosporin A prevent brain death-induced renal allograft dysfunction. Amer J of Transplantation 5: 662.CrossRef

24.

Pratschke, J., M.J. Wilhelm, M. Kusaka, et al. 2000. Accelerated rejection of rat renal allografts from brain dead donors. Annals of Surgery 232: 263.PubMedCrossRef

25.

Kusaka, M., J. Pratschke, M.J. Wilhelm, et al. 2000. Activation of inflammatory mediators in rat renal isografts by donor brain death. Transplantation 69: 405.PubMedCrossRef

26.

van der Hoeven, J.A., S. Lindell, R. van Schilfgaarde, et al. 2001. Donor brain death reduces survival after transplantation in rat livers preserved for 20 hr. Transplantation 72: 1632.PubMedCrossRef

27.

van der Hoeven, J.A., R.J. Ploeg, F. Postema, et al. 1999. Induction of organ dysfunction and up-regulation of inflammatory markers in the liver and kidneys of hypotensive brain dead rats: a model to study marginal organ donors. Transplantation 68: 1884.PubMedCrossRef

28.

Mertes, P.M., K. El Abassi, Y. Jaboin, et al. 1994. Changes in hemodynamic and metabolic parameters following induced brain death in the pig. Transplantation 58: 414.PubMedCrossRef

29.

Mertes, P.M., P. Burtin, J.P. Carteaux, et al. 1994. Changes in hemodynamic performance and oxygen consumption during brain death in the pig. Transplantation Proceedings 26: 229.PubMed

30.

Toyama, H., M. Takada, Y. Suzuki, and Y. Kuroda. 2003. Brain death-induced expression of ICAM-1 and VCAM-1 on rat hepatocytes. Hepatogastroenterology 50: 1854.PubMed

31.

Jassem, W., D.D. Koo, L. Cerundolo, M. Rela, N.D. Heaton, and S.V. Fuggle. 2003. Cadaveric versus living-donor livers: differences in inflammatory markers after transplantation. Transplantation 76: 1599.PubMedCrossRef

32.

Jassem, W., D.D. Koo, L. Cerundolo, M. Rela, et al. 2003. Leukocyte infiltration and inflammatory antigen expression in cadaveric and living-donor livers before transplant. Transplantation 75: 2001.PubMedCrossRef

33.

Hoeger, S., A. Reisenbuechler, U. Gottmann, et al. 2008. Donor dopamine treatment in brain dead rats is associated with an improvement in renal function early after transplantation and a reduction in renal inflammation. Transplant International 21: 1072.PubMed

34.

Kotsch, K., F. Ulrich, A. Reutzel-Selke, et al. 2008. Methylprednisolone therapy in deceased donors reduces inflammation in the donor liver and improves outcome after liver transplantation. Annals of Surgery 248: 1042.PubMedCrossRef

35.

Schnuelle, P., S. Berger, J. de Boer, et al. 2001. Effects of catecholamine application to brain-dead donors on graft survival in solid organ transplantation. Transplantation 72: 455.PubMedCrossRef

Title: Effect of Donor JNK Signal Transduction Inhibition on Transplant Outcome in Brain Dead Rat Model
Authors: Lu Chen
Danfeng Xu
Yi Gao
Xingang Cui
Zunguo Du
Qiang Ding
Xiang Wang
Publication date: 01-02-2012
Publisher: Springer US
Published in: Inflammation / Issue 1/2012
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI: https://doi.org/10.1007/s10753-011-9296-6

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