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Pathology of fatal and resolving Plasmodium berghei cerebral malaria in mice

Published online by Cambridge University Press:  06 April 2009

A. L. Neill  and
N.H. Hunt
A. L. Neill
Affiliation:
Department of Pathology, University of Sydney, N.S.W. 2006, Australia
N.H. Hunt
Affiliation:
Department of Pathology, University of Sydney, N.S.W. 2006, Australia
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Summary

CBA/T6 and Balb/c mice inoculated with Plasmodium berghei ANKA strain (PbA) died from cerebral malaria 6–8 days post-inoculation. DBA/2J mice similarly inoculated developed a non-fatal cerebral malaria, with mild temporary cerebral symptoms, and died between days 15 and 22 from other malaria-related complications. When inoculated with P. berghei K173 (Pb) these mouse strains did not develop a cerebral malaria but died between days 15 and 22 from other malaria-related complications. These mouse strain/parasite strain combinations allow for detailed examination of factors critical in the pathology of murine cerebral malaria. Monastral Blue, a colloid dye, when injected intravascularly between days 0 and 2 into PbA-inoculated CBA (PbA-CBA) or Balb/c (PbA-Balb/c) mice prevented death from cerebral malaria. There was no evidence of increased vascular permeability at this stage. When Monastral Blue was injected between days 5 and 8, there was increased vascular permeability in the kidney, liver, lung, spleen and brain of PbA-CBA and PbA-Balb/c mice. Injection of Monastral Blue into these animals at this time also precipitated cerebral symptoms and death, but not in Pb-infected mice. Endothelial and mononuclear cells phagocytosed, and were coated with, the Monastral Blue particles when the dye was injected between days 5 and 8 into PbA-CBA and PbA-Balb/c mice. Control, uninfected mice did not demonstrate either of these features. Pb-infected mice only demonstrated coated mononuclear cells. Mononuclear cell attachment to the endothelium, increased vascular permeability and increased association of Monastral Blue particles with monocytes and endothelial cells were correlated with cerebral symptoms and death. Monastral Blue is thus a useful agent for studying the roles of mononuclear cells and endothelium in murine cerebral malaria.

Keywords

cerebral malariaPlasmodium bergheimononuclear cellsendotheliumretinablood-brain barrier
Type
Research Article
Information
Parasitology , Volume 105 , Issue 2 , October 1992 , pp. 165 - 175
Copyright
Copyright © Cambridge University Press 1992

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References

REFERENCES

Aikawa, M., Iseki, M., Barnwell, J. W., Taylor, D., Oo, M. M. & Howard, R. J. (1990). The pathology of human cerebral malaria. American Journal of Tropical Medicine and Hygiene 43, 30–7.CrossRefGoogle ScholarPubMed
Benveniste, E. N., Sparacio, S. M. & Bethea, J. R. (1989). Tumour necrosis factor-α enhances interferon-gamma-mediated class II antigen expression on astrocytes. Journal of Neuroimmunology 25, 209–19.CrossRefGoogle ScholarPubMed
Boonpucknavig, V., Boonpucknavig, S., Udomsangpetch, R. & Nitiyanant, P. (1990). An immunofluorescence study of cerebral malaria: A correlation with histopathology. Archives of Pathology and Laboratory Medicine 114, 1028–34.Google ScholarPubMed
Brewster, D. R., Kwiatkowski, D. & White, N. J. (1990). Neurological sequelae of cerebral malaria in children. Lancet 336, 1039–43.CrossRefGoogle ScholarPubMed
Butcher, G. A., Garland, T., Ajdukiewicz, A. B. & Clark, I. A. (1990). Serum tumor necrosis factor associated with malaria in patients in the Solomon Islands. Transactions of the Royal Society of Tropical Medicine and Hygiene 84, 658–61.CrossRefGoogle ScholarPubMed
Cashman, N., Boulet, S., Cragg, L., Bambridge, L. & Antel, J. (1988). Accessory cell competence of human glial cells in mitogenic activation of resting peripheral T cells. Annals of the New York Academy of Science 540, 498–500.CrossRefGoogle ScholarPubMed
Chabasse, D., Drouet, F., Bidault, P., Subra, J. F. & Achard, J. (1981). Forme neurologique on accès pernicieux á Plasmodium Malariae. Discussion physiopathologique apropos d'une observation. Bulletin de la Société de Pathologic Exotique 74, 171–5.Google Scholar
Chan, P. H., Schmidley, W., Fishman, R. A. & Longar, S. M. (1984). Brain injury, oedema, and vascular permeability changes induced by oxygen-derived free radicals. Neurology 34, 315–20.CrossRefGoogle ScholarPubMed
Clark, I. A. (1987). Monokines and lymphokines in malarial pathology. Annals of Tropical Medicine and Parasitology 81, 577–85.CrossRefGoogle ScholarPubMed
Clark, I. A., Chaudhri, G. & Cowden, W. B. (1989). Roles of tumour necrosis factor in the illness and pathology of malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene 83, 436–40.CrossRefGoogle ScholarPubMed
Clark, I. A., Cowden, W. B., Butcher, G. A. & Hunt, N. H. (1987 a). Possible roles of tumour necrosis factor in the pathology of malaria. American Journal of Pathology 129, 192–9.Google ScholarPubMed
Clark, I. A., Hunt, N. H. & Cowden, W. B. (1986). Oxygen-derived free radicals in the pathogenesis of parasitic disease. Advances in Parasitology 25, 1–44.CrossRefGoogle ScholarPubMed
Clark, I. A., Hunt, N. H. & Cowden, W. B. (1987 b). Immunopathology of malaria. In Immune Responses to Parasites (ed. Soulsby, E. J. L.), pp. 1–34. Baton Rouge: CRC Press.Google Scholar
Clark, I. A., Ilschner, S., Macmicking, J. D. & Cowden, W. B. (1990). TNF and Plasmodium berghei ANKA-induced cerebral malaria. Immunological Letters 25, 195–8.CrossRefGoogle ScholarPubMed
Clark, I. A., Rockett, K. A. & Cowden, W. B. (1991). Proposed link between cytokines, nitric oxide and human cerebral malaria. Parasitology Today, 7, 205–7.CrossRefGoogle ScholarPubMed
Endshaw, Y. & Assefa, D. (1990). Cerebral malaria: factors affecting outcome of treatment in suboptimal clinical setting. Journal of Tropical Medicine and Hygiene 93, 44–7.Google Scholar
Fabry, Z., Waldschmidt, M. M., Van Dyk, L., Moore, S. A. & Hart, M. N. (1990). Activation of CD4+ lymphocytes by syngeneic brain microvascular smooth muscle cells. Journal of Immunology 145, 1099–104.CrossRefGoogle ScholarPubMed
Finley, R. W., Mackey, L. J. & Lambert, P.-H. (1982). Virulent P. berghei malaria: prolonged survival and decreased cerebral pathology in cell-deficient nude mice. Journal of Immunology 129, 2213–18.CrossRefGoogle Scholar
Finley, R., Weintraub, J., Louis, J. A., Engers, H. D., Zubler, R. & Lambert, P.-H. (1983). Prevention of cerebral malaria by adoptive transfer of malariaspecific cultured T cells into mice infected with Plasmodium berghei. Journal of Immunology 131, 1522–6.CrossRefGoogle ScholarPubMed
Grau, G. E., Bieler, G., Pointaire, P., De Kossodo, S., Tacchini-Cotier, F., Vassalli, P., Piguet, P. F. & Lambert, P.-H. (1990). Significance of cytokine production and adhesion molecules in malarial immunopathology. Immunological Letters 25, 189–94.CrossRefGoogle ScholarPubMed
Grau, G. E., Fajardo, L. F., Piguet, P.-F., Allet, B., Lambert, P.-H. & Vassalli, P. (1987). Tumour necrosis factor (cachectin) as an essential mediator in murine cerebral malaria. Science 237, 1210–12.CrossRefGoogle ScholarPubMed
Grau, G. E., Heremans, H., Piguet, P.-F., Pointaire, P., Lambert, P.-H., Billiau, A. & Vassalli, P. (1989 a). Monoclonal antibody against interferon gamma can prevent experimental cerebral malaria and its associated overproduction of tumour necrosis factor. Proceedings of the National Academy of Sciences, USA 86, 5572–4.CrossRefGoogle Scholar
Grau, G. E., Kindler, V., Piguet, P.-F., Lambert, P.-H. & Vassalli, P. (1988). Prevention of experimental cerebral malaria by anticytokine antibodies. Interleukin 3 and granulocyte marcophage colonystimulating factor are intermediates in increased tumour necrosis factor production and macrophage accumulation. Journal of Experimental Medicine 168, 1499–504.CrossRefGoogle Scholar
Grau, G. E., Piguet, P.-F., Engers, J. D., Louis, J. A., Vassali, P. & Lambert, P.-H. (1986). L3T4+ T lymphocytes play a major role in the pathogenesis of murine cerebral malaria. Journal of Immunology 137, 2348–54.CrossRefGoogle Scholar
Grau, G. E., Piguet, P.-F., Vassalli, P. & Lambert, P.-H. (1989 b). Tumor-necrosis factor and other cytokines in cerebral malaria: experimental and clinical data. Immunological Reviews 112, 49–70.CrossRefGoogle ScholarPubMed
Grau, G. E., Taylor, T. E., Molyneux, M. E., Wirima, J. J., Vassalli, P., Hommel, M. & Lambert, P.-H. (1989 c). Tumor necrosis factor and disease severity in children with falciparum malaria. New England Journal of Medicine 320, 1586–91.CrossRefGoogle ScholarPubMed
Hart, P. H., Whitty, G. A., Piccoli, D. S. & Hamilton, J. A. (1989). Control by IFN-gamma and PGE2 of TNFα and IL-1 production by human monocytes. Immunology 66, 376–83.Google ScholarPubMed
Jiang, J. B., Yu, S. Y. & Chen, J. M. (1965). A new strain of Plasmodium vivax endemic to China. Acta Scientarum Naturalium Universatis Sunyatseni 1, 131–2.Google Scholar
Kwiatkowski, D., Hill, A. V. S., Sambou, I., Twumasi, P., Castracane, J., Manogue, K. R., Cerami, A., Brewster, D. R. & Greenwood, B. M. (1990). TNF concentration in fatal cerebral, non-fatal cerebral, and uncomplicated Plasmodium falciparum malaria. Lancet 336, 1201–4.CrossRefGoogle ScholarPubMed
Leszczynski, D. & Haeyry, P. (1989). Eicosanoids are regulatory molecules in gamma-interferon-induced endothelial antigenicity and adherence for leucoytes. FEBS Letters 242, 383–6.CrossRefGoogle Scholar
Liew, F. Y. & Cox, F. E. G. (1991). Nonspecific defence mechanism: the role of nitric oxide. Immunology Today 12, A17–A21.CrossRefGoogle ScholarPubMed
Looareesuwan, S., Warrell, D. A., White, N. J., Chanthavanich, P., Warrell., M. J., Chantaratherakitti, S., Changswek, S., Chongmankongcheep, L. & Kanchanaranya, C. (1983). Retinal hemorrhage, a common sign of prognostic significance in cerebral malaria. American Journal of Tropical Medicine and Hygiene 32, 911–15.CrossRefGoogle ScholarPubMed
Mackey, L. J., Hochmann, A., June, C. H., Contreras, C. E. & Lambert, P.-H. (1980). Immunopathological aspects of Plasmodium berghei infection in five strains of mice: II. Immunopathology of cerebral and other tissue lesions during the infection. Clinical and Experimental Immunology 42, 412–20.Google ScholarPubMed
MacPherson, G. G., Warrell, M. J., White, N. J., Looareesuwan, S. & Warrell, D. A. (1985). Human cerebral malaria: A quantitative ultrastructural analysis of parasitized erythrocyte sequestration. American Journal of Pathology 119, 385–401.Google ScholarPubMed
Maegraith, B. G. (1948). Pathological Process in Malaria and Blackwater Fever. Oxford: Blackwell Scientific.Google Scholar
Male, D., Pryce, G., Hughes, C. & Lantos, P. (1990). Lymphocyte migration into brain modelled in vitro: Control by lymphocyte activation, cytokines, and antigen. Cellular Immunology 127, 1–11.CrossRefGoogle ScholarPubMed
Ockenhouse, C. F. & Shear, H. L. (1984). Oxidative killing of the intraerythrocytic malaria parasite Plasmodium yoelii by activated macrophages. Journal of Immunology 132, 424–31.CrossRefGoogle ScholarPubMed
Pober, J. S. (1988). Cytokine-mediated activation of vascular endothelium. Physiology and pathology. American Journal of Pathology 133, 426–33.Google ScholarPubMed
Rest, J. R. (1982). Cerebral malaria in inbred mice: I. A new model and its pathology. Transactions of the Royal Society of Tropical Medicine and Hygiene 76, 410–15.CrossRefGoogle Scholar
Robbins, D. S., Shirazi, Y., Drysdale, B., Leiberman, A., Shin, H. S. & Shin, M. L. (1987). Production of cytotoxic factor for oligodendrocytes by stimulated astrocytes. Journal of Immunology 139, 2593–7.CrossRefGoogle ScholarPubMed
Sawada, M., Kondo, N., Suzumura, A. & Marunouchi, T. (1989). Production of tumor necrosis factor-alpha by microglia and astrocytes in culture. Brain Research 491, 394–7.CrossRefGoogle ScholarPubMed
Schetters, T., Curfs, J., Van Zon, A., Hermsen, C. & Eling, W. (1989). Cerebral lesions in mice infected with Plasmodium berghei are the result of an immunopathological reaction. Transactions of the Royal Society of Tropical Medicine and Hygiene 83 (Suppl.), 103–4.CrossRefGoogle ScholarPubMed
Shaffer, N., Grau, G. E., Hedberg, K., Davachi, F., Lyamba, B., Hightower, A. W., Breman, J. G. & Nguyen-Ding, P. (1991). Tumor necrosis factor and severe malaria. Journal of Infectious Diseases 163, 96–101.CrossRefGoogle ScholarPubMed
Shakib, M. & Cunha-Vaz, J. G. (1966). Studies on the permeability of the blood-retinal barrier. IV. Junctional complexes of the retinal Vessels and their role in the permeability of the blood-retinal barrier. Experimental Eye Research 5, 229–34.CrossRefGoogle ScholarPubMed
Steiniger, B., Schroeder, D., Lueck, R., Luciano, L. & Van Der Meide, P. H. (1990). Gamma interferon treatment in vivo provokes accumulation of activated monocytes in the venous circulation of rats. American Journal of Pathology 136, 967–78.Google ScholarPubMed
Sturchler, D. (1989). How much malaria is there worldwide? Parasitology Today 5, 39–40.CrossRefGoogle Scholar
Taverne, J., Bate, C. A. W. & Playfair, J. H. L. (1990). Malaria exoantigens induce TNF, are toxic and are blocked by T-independent antibody. Immunology Letters 25, 207–12.CrossRefGoogle ScholarPubMed
Thumwood, C. M. (1988). Cerebral malaria. Ph.D. thesis, Australian National University, Canberra.Google Scholar
Thumwood, C. M., Hunt, N. H., Clark, I. A. & Cowden, w. B. (1988). Breakdown of the blood-brain barrier in murine cerebral malaria. Parasitology 96, 579–89.CrossRefGoogle ScholarPubMed
Thumwood, C. M., Hunt, N. H., Cowden, W. B. & Clark, I. A. (1989). Anti-oxidants can prevent cerebral malaria in Plasmodium berghei-infected mice. British Journal of Experimental Pathology 70, 293–303.Google ScholarPubMed
Toro, G. & Roman, G. (1978). Cerebral malaria: disseminated vasculomyelinopathy. Archives of Neurology 35, 271–5.CrossRefGoogle ScholarPubMed
Warrell, D. A., Looareesuwan, S., Phillips, R. E., White, N. J., Warrell, M. J., Chapel, H. M., Areekul, S. & Tharavanij, S. (1986). Function of the bloodcerebrospinal fluid barrier in human cerebral malaria: rejection of the permeability hypothesis. American Journal of Tropical Medicine and Hygiene 35, 882–9.CrossRefGoogle ScholarPubMed
Warrell, D. A., Veal, N., Chanthavanich, P., Karbwang, J., White, N. J., Looareesuwan, S., Phillips, R. E. & Pongpaew, P. (1988). Cerebral anaerobic glycolysis and reduced cerebral oxygen transport in human cerebral malaria. Lancet 2, 534–7.CrossRefGoogle ScholarPubMed
Woodroofe, M. N., Hayes, G. M. & Cuzner, M. L. (1989). Fc receptor density, MHC antigen expression and superoxide production are increased in interferon-gamma-treated microglia isolated from adult rat brain. Immunology 68, 421–6.Google ScholarPubMed
Yoshida, S., Minakawa, T., Takai, N. & Tanaka, R. (1989). Effects of cytokines on cultured microvascular endothelial cells derived from gerbil brain. Neurosurgery 25, 373–7.CrossRefGoogle ScholarPubMed
Zweifach, B. W. (1964). Microcirculatory aspects of tissue injury. Annals of the New York Academy of Science 116, 831–8.CrossRefGoogle ScholarPubMed