Endotoxin-induced gene expression differences in the brain and effects of iNOS inhibition and norepinephrine

详细信息    查看全文

• 作者：Stephanie Wolff (1)
  Sabine Klatt (1)
  Jens C. Wolff (2)
  Jochen Wilhelm (3)
  Ludger Fink (3)
  Manfred Kaps (1)
  Bernhard Rosengarten (1)
  
• 关键词：Sepsis ; Delirium ; Encephalopathy ; Hippocampus ; Chemokines ; Microarrays
• 刊名：Intensive Care Medicine
• 出版年：2009
• 出版时间：April 2009
• 年：2009
• 卷：35
• 期：4
• 页码：730-739
• 全文大小：337KB
• 参考文献：1. Ebersoldt M, Sharshar T, Annane D (2007) Sepsis-associated delirium. Intensive Care Med 33:941-50 CrossRef
  2. Green R, Scott LK, Minagar A, Conrad S (2004) Sepsis associated encephalopathy (SAE): a review. Front Biosci 9:1637-641 CrossRef
  3. Papadopoulos MC, Davies DC, Moss RF, Tighe D, Bennett ED (2000) Pathophysiology of septic encephalopathy: a review. Crit Care Med 28:3019-024 CrossRef
  4. Bello JH, Park M (2007) Sepsis-associated encephalopathy as a differential diagnosis with motor deficit plus altered mental status. Clinics 62:199-02 CrossRef
  5. Eggers V, Schilling A, Kox WJ, Spies C (2003) Septic encephalopathy. Diagnosis und therapy. Anaesthesist 52:294-03 CrossRef
  6. Sharshar T, Annane D, de la Grandmaison GL, Brouland JP, Hopkinson NS, Fran?oise G (2004) The neuropathology of septic shock. Brain Pathol 14:21-3
  7. Hinkelbein J, Schroeck H, Peterka A, Schubert C, Kuschinsky W, Kalenka A (2007) Local cerebral blood flow is preserved in sepsis. Curr Neurovasc Res 4:39-7 CrossRef
  8. Pfister D, Siegemund M, Dell-Kuster S, Smielewski P, Rüegg S, Strebel SP, Marsch SC, Pargger H, Steiner LA (2008) Cerebral perfusion in sepsis-associated delirium. Crit Care 12:R63 CrossRef
  9. Lee CC, Lin NT, Hsu YH, Chen HI (2005) Inducible nitric oxide synthase inhibition potentiates multiple organ dysfunction induced by endotoxin in conscious rats. J Cardiovasc Pharmacol 9:139-43
  10. Matejovic M, Krouzecky A, Radej J, Rokyta R Jr, Kralova H, Radermacher P, Novak I (2007) Coagulation and endothelial dysfunction during longterm hyperdynamic porcine bacteremia-effects of selective inducible nitric oxide synthase inhibition. Thromb Haemost 97:304-09
  11. Ahn KS, Noh EJ, Zhao HL, Jung SH, Kang SS, Kim YS (2005) Inhibition of inducible nitric oxide synthase and cyclooxygenase II by / Platycodon grandiflorum saponins via suppression of nuclear factor-kappaB activation in RAW 264.7 cells. Life Sci 76:2315-328 CrossRef
  12. Rosengarten B, Hecht M, Auch D, Ghofrani HA, Schermuly RT, Grimminger F, Kaps M (2007) Microcirculatory dysfunction in the brain precedes changes in evoked potentials in endotoxin-induced sepsis syndrome in rats. Cerebrovasc Dis 23:140-47 CrossRef
  13. R Development Core Team (2007) R: a language and environment for statistical computing. R Foundation for statistical computing, Vienna, Austria. ISBN 3-900051-07-0. Available via DIALOG http://www.R-project.org. Accessed 2007
  14. Smyth GK (2005) Limma: linear models for microarray data. In: Gentleman R, Carey V, Dudoit S, Irizarry R, Huber W (eds) Bioinformatics and computational biology solutions using R and bioconductor. Springer, New York, pp 397-20 CrossRef
  15. Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S, Ellis B, Gautier L, Ge Y, Gentry J, Hornik K, Hothorn T, Huber W, Iacus S, Irizarry R, Leisch F, Li C, Maechler M, Rossini AJ, Sawitzki G, Smith C, Smyth G, Tierney L, Yang JY, Zhang J (2004) Bioconductor: open software development for computational biology and bioinformatics. In: Genome Biol 5:R80. Available via DIALOG http://genomebiology.com/2004/5/10/R80. Accessed 2004
  16. Edwards D (2003) Non-linear normalization and background correction in one-channel cDNA microarray studies. Bioinformatics 19:825-33 CrossRef
  17. Smyth GK, Speed TP (2003) Normalization of cDNA microarray data. Methods 31:265-73 CrossRef
  18. Smyth GK (2004) Linear models and empirical Bayes methods for assessing differential expression in microarray experiments. In: Statistical applications in genetics and molecular biology 3, article 3. Available via DIALOG http://www.bepress.com/sagmb/vol3/iss1/art3. Accessed 2004
  19. Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B 57:289-00
  20. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402-08 CrossRef
  21. Fink L, Kohlhoff S, Stein MM, H?nze J, Weissmann N, Rose F, Akkayagil E, Manz D, Grimminger F, Seeger W, Bohle RM (2002) cDNA array hybridization after laser-assisted microdissection from nonneoplastic tissue. Am J Pathol 160:81-0
  22. Silverman J, Muir WW 3rd (1993) A review of laboratory animal anesthesia with chloral hydrate and chloralose. Lab Anim Sci 43:210-16
  23. Wilhelm J, Muyal JP, Best J, Kwapiszewska G, Stein MM, Seeger W, Bohle RM, Fink L (2006) Systematic comparison of the T7-IVT and SMART-based RNA preamplification techniques for DNA microarray experiments. Clin Chem 52:1161-167 CrossRef
  24. Schneider J, Buness A, Huber W, Volz J, Kioschis P, Hafner M, Poustka A, Sültmann H (2004) Systematic analysis of T7 RNA polymerase based in vitro linear RNA amplification for use in microarray experiments. BMC Genomics 5:29 CrossRef
  25. Puskás LG, Zvara A, Hackler L Jr, Van Hummelen P (2002) RNA amplification results in reproducible microarray data with slight ratio bias. Biotechniques 32:1330-334, 1336, 1338, 1340
  26. Carrol ED, Mankhambo LA, Balmer P, Nkhoma S, Banda DL, Guiver M, Jeffers G, Makwana N, Molyneux EM, Molyneux ME, Smyth RL, Hart CA, Invasive Pneumococcal Disease Study Group (2007) Chemokine responses are increased in HIV-infected Malawian children with invasive pneumococcal disease. J Acquir Immune Defic Syndr 44:443-50 CrossRef
  27. Riese J, Schoolmann S, Denzel C, Herrmann O, Hohenberger W, Haupt W (2002) Effect of abdominal infections on peritoneal and systemic production of interleukin 6 and monocyte chemoattractant protein-1. Shock 17:361-64 CrossRef
  28. Bossink AW, Paemen L, Jansen PM, Hack CE, Thijs LG, Van Damme J (1995) Plasma levels of the chemokines monocyte chemotactic proteins-1 and -2 are elevated in human sepsis. Blood 86:3841-847
  29. Kalehua AN, Nagel JE, Whelchel LM, Gides JJ, Pyle RS, Smith RJ, Kusiak JW, Taub DD (2004) Monocyte chemoattractant protein-1 and macrophage inflammatory protein-2 are involved in both excitotoxin-induced neurodegeneration and regeneration. Exp Cell Res 297:197-11 CrossRef
  30. Eugenin EA, D’Aversa TG, Lopez L, Calderon TM, Berman JW (2003) MCP-1 (CCL2) protects human neurons and astrocytes from NMDA or HIV-tat-induced apoptosis. J Neurochem 85:1299-311 CrossRef
  31. Dimitrijevic OB, Stamatovic SM, Keep RF, Andjelkovic AV (2007) Absence of the chemokine receptor CCR2 protects against cerebral ischemia/reperfusion injury in mice. Stroke 38:1345-353 CrossRef
  32. Abraham E, Kaneko DJ, Shenkar R (1999) Effects of endogenous and exogenous catecholamines on LPS-induced neutrophil trafficking and activation. Am J Physiol 276:L1–L8
  33. Hofstetter C, Boost KA, Hoegl S, Flondor M, Scheller B, Muhl H, Pfeilschifter J, Zwissler B (2007) Norepinephrine and vasopressin counteract anti-inflammatory effects of isoflurane in endotoxemic rats. Int J Mol Med 20:597-04
  34. Tsuda Y, Kobayashi M, Herndon DN, Suzuki F (2008) Impairment of the host’s antibacterial resistance by norepinephrine activated neutrophils. Burns 34:460-66 CrossRef
  35. Blandino P Jr, Barnum CJ, Deak T (2006) The involvement of norepinephrine and microglia in hypothalamic and splenic IL-1beta responses to stress. J Neuroimmunol 173:87-5 CrossRef
  36. Conte D, Holcik M, Lefebvre CA, Lacasse E, Picketts DJ, Wright KE, Korneluk RG (2006) Inhibitor of apoptosis protein cIAP2 is essential for lipopolysaccharide-induced macrophage survival. Mol Cell Biol 26:699-08 CrossRef
  37. Tissier S, Lancel S, Marechal X, Mordon S, Depontieu F, Scherpereel A, Chopin C, Neviere R (2004) Calpain inhibitors improve myocardial dysfunction and inflammation induced by endotoxin in rats. Shock 21:352-57 CrossRef
  38. Scherpereel A, Depontieu F, Grigoriu B, Cavestri B, Tsicopoulos A, Gentina T, Jourdain M, Pugin J, Tonnel AB, Lassalle P (2006) Endocan, a new endothelial marker in human sepsis. Crit Care Med 34:532-37 CrossRef
  39. Semmler A, Okulla T, Sastre M, Dumitrescu-Ozimek L, Heneka MT (2005) Systemic inflammation induces apoptosis with variable vulnerability of different brain regions. J Chem Neuroanat 30:144-57 CrossRef
  
• 作者单位：Stephanie Wolff (1)
  Sabine Klatt (1)
  Jens C. Wolff (2)
  Jochen Wilhelm (3)
  Ludger Fink (3)
  Manfred Kaps (1)
  Bernhard Rosengarten (1)
  
  1. Department of Neurology, Justus-Liebig-University Giessen, Am Steg 14, 35392, Giessen, Germany
  2. Max-Planck-Institute for Heart and Lung Research, 61231, Bad Nauheim, Germany
  3. Department of Pathology, Justus-Liebig-University Giessen, 35392, Giessen, Germany
  

文摘

Purpose We studied gene expression differences in brain homogenate, hippocampus, somatosensory cortex and cerebellum of rats suffering from sepsis-associated delirium and analyzed the effects of norepinephrine and 1,400?W (specific inhibitor of the inducible nitric-oxide synthase). Methods We applied microarray screenings to rat brain homogenate 1, 3 and 4.5?h after lipopolysaccharide (LPS, 5?mg/kg) or 0.9% NaCl treatment. Therapy groups were analyzed after 4.5?h. Validations and compartment specific investigations were carried out by real-time PCR. Results Most striking gene expression differences were seen 4.5?h after LPS administration, especially within the hippocampus (chemokines and endothelial cell-specific molecule 1). Norepinephrine resulted in a discrete chemokine up-regulation, while 1,400?W had hardly any effect. Conclusion Strongest gene regulations were found within the hippocampus. Norepinephrine showed a tendency of having a proinflammatory influence, while 1,400?W had no clear-cut effect onto the gene expression level.