1921
Volume 84, Issue 2
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract.

The ability of trypanosomes to invade the brain and induce an inflammatory reaction is well-recognized. This study uses magnetic resonance imaging (MRI) in conjunction with a murine model of central nervous system (CNS) stage trypanosomiasis to investigate this phenomenon at the level of the blood–brain barrier (BBB). Mice were scanned before and after administration of the contrast agent. Signal enhancement maps were generated, and the percentage signal change was calculated. The severity of the neuroinflammation was also assessed. Statistical analysis of the signal change data revealed a significantly ( = 0.028) higher signal enhancement in mice at 28 days post-infection (least squares mean = 26.709) compared with uninfected animals (6.298), indicating the presence of BBB impairment. Leukocytes were found in the meninges and perivascular space of some blood vessels in the infected mice. This study shows that the integrity of the BBB is compromised during CNS stage trypanosomiasis and that the impairment does not correlate with inflammatory cell infiltration.

Loading

Article metrics loading...

/content/journals/10.4269/ajtmh.2011.10-0487
2011-02-04
2017-11-23
Loading full text...

Full text loading...

/deliver/fulltext/14761645/84/2/344.html?itemId=/content/journals/10.4269/ajtmh.2011.10-0487&mimeType=html&fmt=ahah

References

  1. Kennedy PGE, , 2004. Human African trypanosomiasis of the CNS: current issues and challenges. J Clin Invest 113: 496504.[Crossref]
  2. Kennedy PGE, , 2008. The continuing problem of human African trypanosomiasis (sleeping sickness). Ann Neurol 64: 116126.[Crossref]
  3. Apted FIC Mulligan HW, , 1970. Clinical manifestations and diagnosis of sleeping sickness. , ed. The African Trypanosomiases. London, UK: Allen & Urwin, 661683.
  4. Rodgers J, , 2009. Human African trypanosomiasis, chemotherapy and CNS disease. J Neuroimmunol 211: 1622.[Crossref]
  5. Adams JH, Graham DI, Adams JH, Graham DI, , 1998. Virus and other infections. , eds. An Introduction to Neuropathology. Edinburgh, Scotland: Churchhill Livingstone, 94117.
  6. Atouguia JLM, Kennedy PGE, Davies LE, Kennedy PGE, , 2000. Neurological aspects of human African trypanosomiasis. , eds. Infectious Diseases of the Nervous System. Oxford, UK: Butterworth-Heinemann, 321372.
  7. Adams JH, Haller L, Boa FY, Doua F, Dago A, Konian K, , 1986. Human African trypanosomiasis (T. b. gambiense): a study of 16 fatal cases of sleeping sickness with some observations on acute reactive arsenical encephalopathy. Neuropathol Appl Neurobiol 12: 8194.[Crossref]
  8. Schmidt H, , 1983. The pathogenesis of trypanosomiasis of the CNS. Studies on parasitological and neurohistological findings in Trypanosoma rhodesiense infected vervet monkeys. Virchows Arch A Pathol Anat Histopathol 399: 333343.[Crossref]
  9. Fink E, Schmidt H, , 1979. Meningoencephalitis in chronic Trypanosoma brucei rhodesiense infection of the white mouse. Tropenmed Parasitol 30: 206211.
  10. Poltera AA, Hochmann A, Lambert PH, , 1982. Trypanosoma brucei gambiense: cerebral immunopathology in mice. Acta Trop 39: 205218.
  11. Jennings FW, McNeil PE, Ndung'u JM, Murray M, , 1989. Trypanosomiasis and encephalitis: possible aetiology and treatment. Trans R Soc Trop Med Hyg 83: 518519.[Crossref]
  12. Philip KA, Dascombe MJ, Fraser PA, Pentreath VW, , 1994. Blood-brain barrier damage in experimental African trypanosomiasis. Ann Trop Med Parasitol 88: 607616.[Crossref]
  13. Mulenga C, Mhlanga JD, Kristensson K, Robertson B, , 2001. Trypanosoma brucei brucei crosses the blood-brain barrier while tight junction proteins are preserved in a rat chronic disease model. Neuropathol Appl Neurobiol 27: 7785.[Crossref]
  14. Sabbah P, Brosset C, Imbert P, Bonardel G, Jeandel P, Briant JF, , 1997. Human African trypanosomiasis: MRI. Neuroradiology 39: 708710.[Crossref]
  15. Gill DS, Chatha DS, Carpio-O'Donovan R, , 2003. MR imaging findings in African trypansomiasis. AJNR Am J Neuroradiol 24: 13831385.
  16. Kager PA, Schipper HG, Stam J, Majoie CB, , 2009. Case report: magnetic resonance imaging findings in human African trypanosomiasis: a four-year follow-up study in a patient and review of the literature. Am J Trop Med Hyg 80: 947952.
  17. Braakman HM, van de Molengraft FJ, Hubert WW, Boerman DH, , 2006. Lethal African trypanosomiasis in a traveler: MRI and neuropathology. Neurology 66: 10941096.[Crossref]
  18. Sternberg JM, Rodgers J, Bradley B, MacLean L, Murray M, Kennedy PG, , 2005. Meningoencephalitic African trypanosomiasis: brain IL-10 and IL-6 are associated with protection from neuro-inflammatory pathology. J Neuroimmunol 167: 8189.[Crossref]
  19. Abbott NJ, Chugani DC, Zaharchuk G, Rosen BR, Lo EH, , 1999. Delivery of imaging agents into brain. Adv Drug Deliv Rev 37: 253277.[Crossref]
  20. Kennedy PGE, Rodgers J, Jennings FW, Murray M, Leeman SE, Burke JM, , 1997. A substance P antagonist, RP-67,580, ameliorates a mouse meningoencephalitic response to Trypanosoma brucei brucei . Proc Natl Acad Sci USA 94: 41674170.[Crossref]
  21. Rodgers J, Stone TW, Barrett MP, Bradley B, Kennedy PG, , 2009. Kynurenine pathway inhibition reduces central nervous system inflammation in a model of human African trypanosomiasis. Brain 132: 12591267.[Crossref]
  22. Engelhardt B, , 2008. The blood-central nervous system barriers actively control immune cell entry into the central nervous system. Curr Pharm Des 14: 15551565.[Crossref]
  23. Wolburg H, Wolburg-Buchholz K, Kraus J, Rascher-Eggstein G, Liebner S, Hamm S, Duffner F, Grote EH, Risau W, Engelhardt B, , 2003. Localization of claudin-3 in tight junctions of the blood-brain barrier is selectively lost during experimental autoimmune encephalomyelitis and human glioblastoma multiforme. Acta Neuropathol 105: 586592.
  24. Grab DJ, Nikolskaia O, Kim YV, Lonsdale-Eccles JD, Ito S, Hara T, Fukuma T, Nyarko E, Kim KJ, Stins MF, Delannoy MJ, Rodgers J, Kim KS, , 2004. African trypanosome interactions with an in vitro model of the human blood-brain barrier. J Parasitol 90: 970979.[Crossref]
  25. Nikolskaia OV, de A Lima A, Kim YV, Lonsdale-Eccles JD, Fukuma T, Scharfstein J, Grab DJ, , 2006. Blood-brain barrier traversal by African trypanosomes requires calcium signaling induced by parasite cysteine protease. J Clin Invest 116: 27392747.[Crossref]
  26. Ballabh P, Braun A, Nedergaard M, , 2004. The blood-brain barrier: an overview: structure, regulation, and clinical implications. Neurobiol Dis 16: 113.[Crossref]
  27. Hawkins BT, Davis TP, , 2005. The blood-brain barrier/neurovascular unit in health and disease. Pharmacol Rev 57: 173185.[Crossref]
  28. Bartholomaus I, Kawakami N, Odoardi F, Schlager C, Miljkovic D, Ellwart JW, Klinkert WE, Flugel-Koch C, Issekutz TB, Wekerle H, Flugel A, , 2009. Effector T cell interactions with meningeal vascular structures in nascent autoimmune CNS lesions. Nature 462: 9498.[Crossref]
  29. Reboldi A, Coisne C, Baumjohann D, Benvenuto F, Bottinelli D, Lira S, Uccelli A, Lanzavecchia A, Engelhardt B, Sallusto F, , 2009. C-C chemokine receptor 6-regulated entry of TH-17 cells into the CNS through the choroid plexus is required for the initiation of EAE. Nat Immunol 10: 514523.[Crossref]
  30. Ransohoff RM, , 2009. Immunology: in the beginning. Nature 462: 4142.[Crossref]
  31. MacLean L, Odiit M, MacLeod A, Morrison L, Sweeney L, Cooper A, Kennedy PG, Sternberg JM, , 2007. Spatially and genetically distinct African Trypanosome virulence variants defined by host interferon-gamma response. J Infect Dis 196: 16201628.[Crossref]
  32. Amin DN, Rottenberg ME, Thomsen AR, Mumba D, Fenger C, Kristensson K, Buscher P, Finsen B, Masocha W, , 2009. Expression and role of CXCL10 during the encephalitic stage of experimental and clinical African trypanosomiasis. J Infect Dis 200: 15561565.[Crossref]
  33. Masocha W, Robertson B, Rottenberg ME, Mhlanga J, Sorokin L, Kristensson K, , 2004. Cerebral vessel laminins and IFN-gamma define Trypanosoma brucei brucei penetration of the blood-brain barrier. J Clin Invest 114: 689694.[Crossref]
  34. Kennedy PGE, Rodgers J, Bradley B, Hunt SP, Gettinby G, Leeman SE, de Felipe C, Murray M, , 2003. Clinical and neuroinflammatory responses to meningoencephalitis in substance P receptor knockout mice. Brain 126: 16831690.[Crossref]
  35. Liao CW, Cho WL, Kao TC, Su KE, Lin YH, Fan CK, , 2008. Blood-brain barrier impairment with enhanced SP, NK-1R, GFAP and claudin-5 expressions in experimental cerebral toxocariasis. Parasite Immunol 30: 525534.[Crossref]
  36. St'astny F, Skultetyova I, Pliss L, Jezova D, , 2000. Quinolinic acid enhances permeability of rat brain microvessels to plasma albumin. Brain Res Bull 53: 415420.[Crossref]
  37. Sanderson L, Dogruel M, Rodgers J, Bradley B, Thomas SA, , 2008. The blood-brain barrier significantly limits eflornithine entry into Trypanosoma brucei brucei infected mouse brain. J Neurochem 107: 11361146.
  38. Sanderson L, Dogruel M, Rodgers J, De Koning H, Thomas SA, , 2009. Pentamidine movement across the murine blood-brain and blood-CSF barriers; effect of trypanosome infection, combination therapy, P-glycoprotein and MRP. J Pharmacol Exp Ther 329: 967977.[Crossref]
  39. World Health Organization, 1998. Control and Surveillance of African Trypanosomiaisis. World Health Organization Technical Report Series 881. Geneva, Switzerland: World Health Organization, 1113.
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.2011.10-0487
Loading
/content/journals/10.4269/ajtmh.2011.10-0487
Loading

Data & Media loading...

  • Received : 01 Sep 2010
  • Accepted : 02 Nov 2010

Most Cited This Month

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