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Trypanosomiasis and the brain

Published online by Cambridge University Press:  23 December 2009

JEAN RODGERS
JEAN RODGERS*
Affiliation:
Institute of Comparative Medicine, Faculty of Veterinary Medicine, University of Glasgow, Bearsden Road, GlasgowG61 1QH
*
*Tel.: +44 101 330 3797. Fax: +44 141 330 5603. Email: [email protected]
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Summary

Neurological involvement following trypanosome infection has been recognised for over a century. However, there are still many unanswered questions concerning the mechanisms used by the parasite to gain entry to the CNS and the pathogenesis of the resulting neuroinflammatory reaction. There is a paucity of material from human cases of the disease therefore the majority of current research relies on the use of animal models of trypanosome infection. This review reports contemporary knowledge, from both animal models and human samples, regarding parasite invasion of the CNS and the neuropathological changes that accompany trypanosome infection and disease progression. The effects of trypanosomes on the blood-brain barrier are discussed and possible key molecules in parasite penetration of the barrier highlighted. Changes in the balance of CNS cytokines and chemokines are also described. The article closes by summarising the effects of trypanosome infection on the circadian sleep-wake cycle, and sleep structure, in relation to neuroinflammation and parasite location within the CNS. Although a great deal of progress has been made in recent years, the advent and application of sophisticated analysis techniques, to decipher the complexities of HAT pathogenesis, herald an exciting and rewarding period for advances in trypanosome research.

Keywords

Human African trypanosomiasisCNSneuroinflammationmouse modelcytokinechemokinesleeping sickness
Type
Research Article
Information
Parasitology , Volume 137 , Special Issue 14: African trypanosomiasis: New insights for disease control , December 2010 , pp. 1995 - 2006
Copyright
Copyright © Cambridge University Press 2009

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References

REFERENCES

Abbott, N. J., Ronnback, L. and Hansson, E. (2006). Astrocyte-endothelial interactions at the blood-brain barrier. Nature Reviews in Neuroscience 7, 41–53.CrossRefGoogle ScholarPubMed
Abdulla, M. H., O'Brien, T., Mackey, Z. B., Sajid, M., Grab, D. J. and McKerrow, J. H. (2008). RNA Interference of Trypanosoma brucei Cathepsin B and L affects disease progression in a mouse model. PLoS Neglected Tropical Diseases 2, e298.CrossRefGoogle ScholarPubMed
Adams, J. H. and Graham, D. I. (1998). Virus and other infections. In An introduction to Neuropathology (ed. Adams, J. H. and Graham, D. I.), pp. 94–117. Churchhill Livingstone, Edinburgh.Google Scholar
Adams, J. H., Haller, L., Boa, F. Y., Doua, F., Dago, A. and 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. Neuropathology and Applied Neurobiology 12, 81–94.CrossRefGoogle Scholar
Amin, D. N., Masocha, W., Ngan'dwe, K., Rottenberg, M. and Kristensson, K. (2008). Suramin and minocycline treatment of experimental African trypanososmiasis at an early stage of parasite brain invasion. Acta Tropica 106, 72–74.CrossRefGoogle ScholarPubMed
Anthoons, J. A. M. S., Van Marck, E. A. E., Gigase, P. L. J. and Stevens, W. J. (1989). Immunohistochemical characterization of the mononuclear cells in the brain of the rat with experimental chronic Trypanosoma brucei gambiense infection. Parasitology Research 75, 251–256.CrossRefGoogle ScholarPubMed
Apted, F. I. C. (1970). Clinical manifestations and diagnosis of sleeping sickness. In The African Trypanosomiases (ed. Mulligan, H. W.), pp. 661–683. Allen & Urwin, London.Google Scholar
Atouguia, J. L. M. and Kennedy, P. G. E. (2000). Neurological aspects of human African trypanosomiasis. In Infectious Diseases of the Nervous System (ed. Davies, Larry E. and Kennedy, Peter G. E.), pp. 321–372. Butterworth-Heinemann, Oxford.Google Scholar
Barrett, M. P., Boykin, D. W., Brun, R. and Tidwell, R. R. (2007). Human African trypanosomiasis: pharmacological re-engagement with a neglected disease. British Journal of Pharmacology 152, 1155–1171.CrossRefGoogle ScholarPubMed
Bentivoglio, M., Grassi-Zucconi, G., Olsson, T. and Kristensson, K. (1994). Trypanosoma brucei and the nervous system. Trends in Neuroscience 17, 325–329.CrossRefGoogle ScholarPubMed
Bentivoglio, M. and Kristensson, K. (2007). Neural-immune interactions in disorders of sleep-wakefulness organization. Trends in Neuroscience 30, 645–652.CrossRefGoogle ScholarPubMed
Braakman, H. M., van de Molengraft, F. J., Hubert, W. W. and Boerman, D. H. (2006). Lethal African trypanosomiasis in a traveler: MRI and neuropathology. Neurology 66, 1094–1096.CrossRefGoogle Scholar
Buguet, A., Bisser, S., Josenando, T., Chapotot, F. and Cespuglio, R. (2005). Sleep structure: a new diagnostic tool for stage determination in sleeping sickness. Acta Tropica 93, 107–117.CrossRefGoogle ScholarPubMed
Buguet, A., Bourdon, L., Bouteille, B., Cespuglio, R., Vincendeau, P., Radomski, M. W. and Dumas, M. (2001). The duality of sleeping sickness: focusing on sleep. Sleep Medicine Reviews 5, 139–153.CrossRefGoogle ScholarPubMed
Calwell, H. (1937). The pathology of the brain in Rhodesian trypanosomiasis. Transactions of the Royal Society of Tropical Medical and Hygiene 30, 611–624.CrossRefGoogle Scholar
Checkley, A. M., Pepin, J., Gibson, W. C., Taylor, M. N., Jager, H. R. and Mabey, D. C. (2007). Human African trypanosomiasis: diagnosis, relapse and survival after severe melarsoprol-induced encephalopathy. Transactions of the Royal Society of Tropical Medical and Hygiene 101, 523–526.CrossRefGoogle ScholarPubMed
Chianella, S., Semprevivo, M., Peng, Z. C., Zaccheo, D., Bentivoglio, M. and Grassi-Zucconi, G. (1999). Microglia activation in a model of sleep disorder: an immunohistochemical study in the rat brain during Trypanosoma brucei infection. Brain Research 832, 54–62.CrossRefGoogle Scholar
Coogan, A. N. and Wyse, C. A. (2008). Neuroimmunology of the circadian clock. Brain Research 1232, 104–112.CrossRefGoogle ScholarPubMed
Courtioux, B., Boda, C., Vatunga, G., Pervieux, L., Josenando, T., M'Eyi, P. M., Bouteille, B., Jauberteau-Marchan, M. O. and Bisser, S. (2006). A link between chemokine levels and disease severity in human African trypanosomiasis. International Journal for Parasitology 36, 1057–1065.CrossRefGoogle ScholarPubMed
Doua, F., Miezan, T. W., Sanon, S. Jr., Boa, Y. F. and Baltz, T. (1996). The efficacy of pentamidine in the treatment of early-late stage Trypanosoma brucei gambiense trypanosomiasis. American Journal of Tropical Medicine and Hygiene 55, 586–588.CrossRefGoogle ScholarPubMed
Fink, E. and Schmidt, H. (1979). Meningoencephalitis in chronic Trypanosoma brucei rhodesiense infection of the white mouse. Tropenmedizin und Parasitologie 30, 206–211.Google ScholarPubMed
Gill, D. S., Chatha, D. S. and Carpio-O'Donovan, R. (2003). MR imaging findings in African trypansomiasis. American Journal of Neuroradiology 24, 1383–1385.Google ScholarPubMed
Grab, D. J. and Kennedy, P. G. (2008). Traversal of human and animal trypanosomes across the blood-brain barrier. Journal of NeuroVirology 14, 344–351.CrossRefGoogle ScholarPubMed
Grab, D. J., Nikolskaia, O., Kim, Y. V., Lonsdale-Eccles, J. D., Ito, S., Hara, T., Fukuma, T., Nyarko, E., Kim, K. J., Stins, M. F., Delannoy, M. J., Rodgers, J. and Kim, K. S. (2004). African trypanosome interactions with an in vitro model of the human blood-brain barrier. Journal of Parasitology 90, 970–979.CrossRefGoogle Scholar
Grassi-Zucconi, G., Harris, J. A., Mohammed, A. H., Ambrosini, M. V., Kristensson, K. and Bentivoglio, M. (1995). Sleep fragmentation, and changes in locomotor activity and body temperature in trypanosome-infected rats. Brain Research Bulletin 37, 123–129.CrossRefGoogle ScholarPubMed
Grassi-Zucconi, G., Semprevivo, M., Mocaer, E., Kristensson, K. and Bentivoglio, M. (1996). Melatonin and its new agonist S-20098 restore synchronized sleep fragmented by experimental trypanosome infection in the rat. Brain Research Bulletin 39, 63–68.CrossRefGoogle ScholarPubMed
Hawkins, B. T. and Davis, T. P. (2005). The blood-brain barrier/neurovascular unit in health and disease. Pharmacological Reviews 57, 173–185.CrossRefGoogle ScholarPubMed
Hunter, C. A., Gow, J. W., Kennedy, P. G., Jennings, F. W. and Murray, M. (1991). Immunopathology of experimental African sleeping sickness: detection of cytokine mRNA in the brains of Trypanosoma brucei brucei-infected mice. Infection and Immunity 59, 4636–4640.CrossRefGoogle ScholarPubMed
Hunter, C. A., Jennings, F. W., Adams, J. H., Murray, M. and Kennedy, P. G. (1992 a). Subcurative chemotherapy and fatal post-treatment reactive encephalopathies in African trypanosomiasis. Lancet 339, 956–958.CrossRefGoogle ScholarPubMed
Hunter, C. A., Jennings, F. W., Kennedy, P. G. and Murray, M. (1992 b). Astrocyte activation correlates with cytokine production in central nervous system of Trypanosoma brucei brucei-infected mice. Laboratory Investigation 67, 635–642.Google ScholarPubMed
Hunter, C. A. and Kennedy, P. G. (1992). Immunopathology in central nervous system human African trypanosomiasis. Journal of Neuroimmunology 36, 91–95.CrossRefGoogle ScholarPubMed
Jennings, F. W., Gichuki, C. W., Kennedy, P. G., Rodgers, J., Hunter, C. A., Murray, M. and Burke, J. M. (1997). The role of the polyamine inhibitor eflornithine in the neuropathogenesis of experimental murine African trypanosomiasis. Neuropathology and Applied Neurobiology 23, 225–234.CrossRefGoogle ScholarPubMed
Johansson, P. A., Dziegielewska, K. M., Liddelow, S. A. and Saunders, N. R. (2008). The blood-CSF barrier explained: when development is not immaturity. Bioessays 30, 237–248.CrossRefGoogle Scholar
Kennedy, P. G. (1999). The pathogenesis and modulation of the post-treatment reactive encephalopathy in a mouse model of Human African Trypanosomiasis. Journal of Neuroimmunology 100, 36–41.CrossRefGoogle Scholar
Kennedy, P. G. (2004). Human African trypanosomiasis of the CNS: current issues and challenges. Journal of Clinical Investigation 113, 496–504.CrossRefGoogle ScholarPubMed
Kennedy, P. G. (2006). Diagnostic and neuropathogenesis issues in human African trypanosomiasis. International Journal for Parasitology 36, 505–512.CrossRefGoogle ScholarPubMed
Kennedy, P. G., Rodgers, J., Bradley, B., Hunt, S. P., Gettinby, G., Leeman, S. E., de Felipe, C. and Murray, M. (2003). Clinical and neuroinflammatory responses to meningoencephalitis in substance P receptor knockout mice. Brain 126, 1683–1690.CrossRefGoogle ScholarPubMed
Kennedy, P. G., Rodgers, J., Jennings, F. W., Murray, M., Leeman, S. E. and Burke, J. M. (1997). A substance P antagonist, RP-67,580, ameliorates a mouse meningoencephalitic response to Trypanosoma brucei brucei. Proceedings of the National Academy of Sciences, USA 94, 4167–4170.CrossRefGoogle ScholarPubMed
Krueger, J. M., Obal, F. J., Fang, J., Kubota, T. and Taishi, P. (2001). The role of cytokines in physiological sleep regulation. Annals of New York Academy of Sciences 933, 211–221.CrossRefGoogle ScholarPubMed
Lejon, V., Lardon, J., Kenis, G., Pinoges, L., Legros, D., Bisser, S., N'Siesi, X., Bosmans, E. and Buscher, P. (2002). Interleukin (IL)-6, IL-8 and IL-10 in serum and CSF of Trypanosoma brucei gambiense sleeping sickness patients before and after treatment. Transactions of the Royal Society of Tropical Medical and Hygiene 96, 329–333.CrossRefGoogle ScholarPubMed
Lejon, V., Legros, D., Savignoni, A., Etchegorry, M. G., Mbulamberi, D. and Buscher, P. (2003 a). Neuro-inflammatory risk factors for treatment failure in “early second stage” sleeping sickness patients treated with pentamidine. Journal of Neuroimmunology 144, 132–138.CrossRefGoogle ScholarPubMed
Lejon, V., Reiber, H., Legros, D., Dje, N., Magnus, E., Wouters, I., Sindic, C. J. and Buscher, P. (2003 b). Intrathecal immune response pattern for improved diagnosis of central nervous system involvement in trypanosomiasis. Journal of Infectious Diseases 187, 1475–1483.CrossRefGoogle ScholarPubMed
Lundkvist, G. B., Christenson, J., ElTayeb, R. A. K., Peng, Z.-C., Grillner, P., Mhlanga, J., Bentivoglio, M. and Kristensson, K. (1998 a). Altered neuronal activity rhythm and glutamate receptor expression in the suprachiasmatic nuclei of Trypanosoma brucei infected rats. Journal of Neuropathology and Experimental Neurology 57, 21–29.CrossRefGoogle ScholarPubMed
Lundkvist, G. B., Hill, R. H. and Kristensson, K. (2002). Disruption of circadian rhythms in synaptic activity of the suprachiasmatic nuclei by African trypanosomes and cytokines. Neurobiology of Disease 11, 20–27.CrossRefGoogle ScholarPubMed
Lundkvist, G. B., Kristensson, K. and Bentivoglio, M. (2004). Why trypanosomes cause sleeping sickness. Physiology (Bethesda) 19, 198–206.Google ScholarPubMed
Lundkvist, G. B., Robertson, B., Mhlanga, D. M., Rottenberg, M. E. and Kristensson, K. (1998 b). Expression of an oscillating interferon-gamma receptor in the suprachiasmstic nuclei. NeuroReport 9, 1059–1063.CrossRefGoogle ScholarPubMed
MacLean, L., Odiit, M., MacLeod, A., Morrison, L., Sweeney, L., Cooper, A., Kennedy, P. G. and Sternberg, J. M. (2007). Spatially and genetically distinct African Trypanosome virulence variants defined by host interferon-gamma response. Journal of Infectious Diseases 196, 1620–1628.CrossRefGoogle ScholarPubMed
MacLean, L., Odiit, M. and Sternberg, J. M. (2001). Nitric oxide and cytokine synthesis in human African trypanosomiasis. Journal of Infectious Diseases 184, 1086–1090.CrossRefGoogle ScholarPubMed
MacLean, L., Odiit, M., and Sternberg, J. M. (2006). Intrathecal cytokine responses in Trypanosoma brucei rhodesiense sleeping sickness patients. Transactions of the Royal Society of Tropical Medical and Hygiene 100, 270–275.CrossRefGoogle ScholarPubMed
Man, S., Ubogu, E. E. and Ransohoff, R. M. (2007). Inflammatory cell migration into the central nervous system: a few new twists on an old tale. Brain Pathology 17, 243–250.CrossRefGoogle Scholar
Masocha, W., Robertson, B., Rottenberg, M. E., Mhlanga, J., Sorokin, L. and Kristensson, K. (2004). Cerebral vessel laminins and IFN-gamma define Trypanosoma brucei brucei penetration of the blood-brain barrier. Journal of Clinical Investigation 114, 689–694.CrossRefGoogle ScholarPubMed
Masocha, W., Rottenberg, M. E. and Kristensson, K. (2006). Minocycline impedes African trypanosome invasion of the brain in a murine model. Antimicrobial Agents and Chemotherapy 50, 1798–1804.CrossRefGoogle ScholarPubMed
Masocha, W., Rottenberg, M. E., and Kristensson, K. (2007). Migration of African trypanosomes across the blood-brain barrier. Physiology and Behavior 92, 110–114.CrossRefGoogle ScholarPubMed
McCarley, R. W. (2007). Neurobiology of REM and NREM sleep. Sleep Medicine 8, 302–330.CrossRefGoogle ScholarPubMed
Montmayeur, A., Brosset, C., Imbert, P. and Buguet, A. (1994). [The sleep-wake cycle during Trypanosoma brucei rhodesiense human African trypanosomiasis in 2 French parachutists]. Bulletin de la Societe de Pathologie Exotique 87, 368–371.Google ScholarPubMed
Mott, F. W. (1907). Histological observations on the changes in the nervous system in trypanosome infections especially sleeping sickness and their relation to syphilitic lesions of the nervous system. Archives of Neurology 3, 581–646.Google Scholar
Mulenga, C., Mhlanga, J. D., Kristensson, K. and Robertson, B. (2001). Trypanosoma brucei brucei crosses the blood-brain barrier while tight junction proteins are preserved in a rat chronic disease model. Neuropathology and Applied Neurobiology 27, 77–85.CrossRefGoogle Scholar
Nikolskaia, O. V., de A. Lima, A. P., Kim, Y. V., Lonsdale-Eccles, J. D., Fukuma, T., Scharfstein, J. and Grab, D. J. (2006 a). Blood-brain barrier traversal by African trypanosomes requires calcium signaling induced by parasite cysteine protease. Journal of Clinical Investigation 116, 2739–2747.CrossRefGoogle ScholarPubMed
Nikolskaia, O. V., de A. Lima, A. P., Kim, Y. V., Lonsdale-Eccles, J. D., Fukuma, T., Scharfstein, J. and Grab, D. J. (2008). Blood-brain barrier traversal by African trypanosomes requires calcium signaling induced by parasite cysteine protease (corrigendum). Journal of Clinical Investigation 118, 1974.CrossRefGoogle Scholar
Nikolskaia, O. V., Kim, Y. V., Kovbasnjuk, O., Kim, K. J. and Grab, D. J. (2006 b). Entry of Trypanosoma brucei gambiense into microvascular endothelial cells of the human blood-brain barrier. International Journal for Parasitology 36, 513–519.CrossRefGoogle ScholarPubMed
Obal, F. Jr. and Krueger, J. M. (2003). Biochemical regulation of non-rapid-eye-movement sleep. Frontiers in Bioscience 8, d520–d550.Google ScholarPubMed
Opp, M. R. (2005). Cytokines and sleep. Sleep Medicine Reviews 9, 355–364.CrossRefGoogle ScholarPubMed
Ouwe-Missi-Oukem-Boyer, O., Mezui-Me-Ndong, J., Boda, C., Lamine, I., Labrousse, F., Bisser, S. and Bouteille, B. (2006). The vervet monkey (Chlorocebus aethiops) as an experimental model for Trypanosoma brucei gambiense human African trypanosomiasis: a clinical, biological and pathological study. Transactions of the Royal Society of Tropical Medical and Hygiene 100, 427–436.CrossRefGoogle ScholarPubMed
Peng, Z. C., Kristensson, K. and Bentivoglio, M. (1994). Dysregulation of photic induction of Fos-related protein in the biological clock during experimental trypanosomiasis. Neuroscience Letters 182, 104–106.CrossRefGoogle ScholarPubMed
Pentreath, V. W., Baugh, P. J. and Lavin, D. R. (1994). Sleeping sickness and the central nervous system. Onderstepoort Journal of Veterinary Research 6, 369–377.Google Scholar
Pentreath, V. W. (1989). Neurobiology of sleeping sickness. Parasitology Today 5, 215–218.CrossRefGoogle ScholarPubMed
Pepin, J. and Milord, F. (1994). The treatment of human African trypanosomiasis. Advances in Parasitology 33, 1–47.CrossRefGoogle ScholarPubMed
Philip, K. A., Dascombe, M. J., Fraser, P. A. and Pentreath, V. W. (1994). Blood-brain barrier damage in experimental African trypanosomiasis. Annals of Tropical Medicine and Parasitology 88, 607–616.CrossRefGoogle ScholarPubMed
Poltera, A. A., Hochmann, A., Rudin, W. and Lambert, P. H. (1980). Trypanosoma brucei brucei: a model for cerebral trypanosomiasis in mice – an immunological, histological and electronmicroscopic study. Clinical and Experimental Immunology 40, 496–507.Google Scholar
Poltera, A. A., Sayer, P. D., Brighouse, G., Bovell, D. and Rudin, W. (1985). Immunopathological aspects of trypanosomal meningoencephalitis in vervet monkeys after relapse following Berenil treatment. Transactions of the Royal Society of Tropical Medical and Hygiene 79, 527–531.CrossRefGoogle ScholarPubMed
Quan, N., He, L. and Lai, W. (2003). Intraventricular infusion of antagonists of IL-1 and TNF alpha attenuates neurodegeneration induced by the infection of Trypanosoma brucei. Journal of Neuroimmunology 138, 92–98.CrossRefGoogle ScholarPubMed
Quan, N., Mhlanga, J. D., Whiteside, M. B., McCoy, A. N., Kristensson, K. and Herkenham, M. (1999). Chronic overexpression of proinflammatory cytokines and histopathology in the brains of rats infected with Trypanosoma brucei. Journal of Comparative Neurology 414, 114–130.3.0.CO;2-G>CrossRefGoogle ScholarPubMed
Radomski, M. W., Buguet, A., Bogui, P., Doua, F., Lonsdorfer, A., Tapie, P. and Dumas, M. (1994). Disruptions in the secretion of cortisol, prolactin, and certain cytokines in human African trypanosomiasis patients. Bulletin de la Societe de Pathologie Exotique 87, 376–379.Google ScholarPubMed
Rodgers, J., Bradley, B. and Kennedy, P. G. (2007). Combination chemotherapy with a substance P receptor antagonist (aprepitant) and melarsoprol in a mouse model of human African trypanosomiasis. Parasitology International 56, 321–324.CrossRefGoogle Scholar
Rodgers, J., Stone, T., Barrett, M. P., Bradley, B. and Kennedy, P. G. E. (2009). Kynurenine pathway inhibition reduces CNS inflammation in a model of human African trypanosomiasis. Brain 132, 1259–1267.CrossRefGoogle Scholar
Sabbah, P., Brosset, C., Imbert, P., Bonardel, G., Jeandel, P. and Briant, J. F. (1997). Human African trypanosomiasis: MRI. Neuroradiology 39, 708–710.CrossRefGoogle ScholarPubMed
Sajid, M. and McKerrow, J. H. (2002). Cysteine proteases of parasitic organisms. Molecular and Biochemical Parasitology 120, 1–21.CrossRefGoogle ScholarPubMed
Saunders, N. R., Ek, C. J., Habgood, M. D. and Dziegielewska, K. M. (2008). Barriers in the brain: a renaissance? Trends in Neuroscience 31, 279–286.CrossRefGoogle ScholarPubMed
Schmidt, H. (1983). The pathogenesis of trypanosomiasis of the CNS. Studies on parasitological and neurohistological findings in trypanosoma rhodesiense infected vervet monkeys. Virchows Archiv A – Pathological Anatomy and Histopathology 399, 333–343.CrossRefGoogle ScholarPubMed
Schmidt, H. and Sayer, P. (1982). Trypanosoma brucei rhodesiense infection in vervet monkeys. I. Parasitologic, histologic, immunologic and histologic results. Tropenmedizin und Parasitologie 33, 249–254.Google ScholarPubMed
Schultzberg, M., Ambatsis, M., Samuelsson, E. B., Kristensson, K. and Van Meirvenne, N. (1988). Spread of Trypanosoma brucei to the nervous system: early attack on circumventricular organs and sensory ganglia. Journal of Neuroscience Research 21, 56–61.CrossRefGoogle Scholar
Sharafeldin, A., Eltayeb, R., Pashenkov, M. and Bakhiet, M. (2000). Chemokines are produced in the brain early during the course of experimental African trypanosomiasis. Journal of Neuroimmunology 103, 165–170.CrossRefGoogle ScholarPubMed
Sharafeldin, A., Hamadien, M., Diab, A., Li, H., Shi, F. and Bakhiet, M. (1999). Cytokine profiles in the central nervous system and the spleen during the early course of experimental African trypanosomiasis. Scandanavian Journal of Immunology 50, 256–261.CrossRefGoogle ScholarPubMed
Sixt, M., Engelhardt, B., Pausch, F., Hallmann, R., Wendler, O. and Sorokin, L. M. (2001). Endothelial cell laminin isoforms, laminins 8 and 10, play decisive roles in T cell recruitment across the blood-brain barrier in experimental autoimmune encephalomyelitis. Journal of Cell Biology 153, 933–946.CrossRefGoogle Scholar
Sternberg, J. M., Rodgers, J., Bradley, B., MacLean, L., Murray, M. and Kennedy, P. G. (2005). Meningoencephalitic African trypanosomiasis: Brain IL-10 and IL-6 are associated with protection from neuro-inflammatory pathology. Journal of Neuroimmunology 167, 81–89.CrossRefGoogle ScholarPubMed
Toth, L. A., Tolley, E. A., Broady, R., Blakely, B. and Krueger, J. M. (1994). Sleep during experimental trypanosomiasis in rabbits. Proceedings of the Society for Experimental Biology and Medicine 205, 174–181.CrossRefGoogle ScholarPubMed
WHO (1998). Control and surveillance of African trypanosomiaisis. WHO technical report series, Geneva 881, 1–113.Google Scholar
Zlokovic, B. V. (2008). The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron 57, 178–201.CrossRefGoogle ScholarPubMed