1887

Abstract

A breakdown of the blood-brain barrier occurred in mice inoculated intracerebrally (i.c.) or intraperitoneally (i.p.) with dengue virus type 2 (DEN2). This resulted in leakage of protein-bound Evans blue dye and Cr-labelled erythrocytes into the brain tissue. The leakage increased with time after infection and coincided with an increase of a DEN2-induced cytokine, the cytotoxic factor (CF), in the spleens of such mice. The titres of virus in the brain increased exponentially in i.c. inoculated mice but the virus was not detected in brains of mice given DEN2 by the i.p. route. Similar breakdown of the blood-brain barrier also occurred in mice inoculated intravenously with CF; the damage was dose-dependent and the vascular integrity was restored during the 3 h period after inoculation. Treatment of mice with antihistamine drugs, blocking H1 or H2 receptors, decreased the DEN2-induced protein leakage by up to 50% in i.c. inoculated mice and up to 92% in those inoculated i.p. Indomethacin, a prostaglandin synthetase inhibitor, had no effect. In i.c. inoculated mice protein leakage was inhibited by about 60% by treatment with CF-specific (CFA) or DEN2-specific antisera (DEN2A) whereas protection was complete with the combined treatment with both antisera. On the other hand, in i.p. inoculated mice the inhibition of protein leakage was 80 to 89% with CFA. These findings show a breakdown of the blood-brain barrier leading to cerebral oedema during DEN2 infection which is mediated via the release of histamine by a virus-induced cytokine.

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1991-04-01
2022-08-17
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References

  1. Agrawal D. K., Tandon P., Chaturvedi U. C., Kumar A. 1978; Biochemical study of certain enzymes and metabolites of the carbohydrate metabolism in the skeletal muscle of the dengue virus-infected mice. Journal of General Virology 40:399–408
    [Google Scholar]
  2. Chaturvedi U. C., Tandon P., Mathur A. 1977; Effect of immunosuppression on dengue virus infection in mice. Journal of General Virology 36:449–458
    [Google Scholar]
  3. Chaturvedi U. C., Tandon P., Mathur A., Kumar A. 1978; Host defence mechanisms against dengue virus infection of mice. Journal of General Virology 39:293–302
    [Google Scholar]
  4. Chaturvedi U. C., Bhargava A., Mathur A. 1980; Production of cytotoxic factor in the spleen of dengue virus-infected mice. Immunology 40:665–671
    [Google Scholar]
  5. Dalakoti H., Chaturvedi U. C., Mathur A. 1983; Studies on dengue virus-induced cytotoxic factor. Indian Journal of Experimental Biology 21:375–378
    [Google Scholar]
  6. Dhawan R., Khanna M., Chaturvedi U. C., Mathur A. 1990a; Effect of dengue virus induced cytotoxin on capillary permeability. International Journal of Experimental Pathology 71:83–89
    [Google Scholar]
  7. Dhawan R., Khanna M., Chaturvedi U. C., Mathur A., Rai R. N. 1990b; Role of Ca2+ in induction and secretion of dengue virus-induced cytokines. Journal of Biosciences 15: (in press)
    [Google Scholar]
  8. Dhawan R., Chaturvedi U. C., Khanna M., Mathur A., Tekwani B. L., Pandey V. C. 1991b; Obligatory role of Ca2+ in the cytotoxic activity of dengue virus-induced cytotoxin. International Journal of Experimental Pathology 72:31–39
    [Google Scholar]
  9. Grau G. E., Fajardo L. F., Piguet P. F., Allet B., Lambert P. H., Vassalli P. 1987; Tumor necrosis factor (cachectin) as an essential mediator in murine cerebral malaria. Science 237:1210–1212
    [Google Scholar]
  10. Halstead S. B. 1980; Dengue haemorrhagic fever – a public health problem and a field for research. Bulletin of the World Health Organization 58:1–21
    [Google Scholar]
  11. Halstead S. B. 1988; Pathogenesis of dengue: challenges to molecular biology. Science 239:476–481
    [Google Scholar]
  12. Khanna M., Chaturvedi U. C., Mathur A. 1988; Abrogation of helper T cells by dengue virus-induced cytotoxic factor. Current Science 57:411–414
    [Google Scholar]
  13. Khanna M., Chaturvedi U. C., Srinivasa B. R., Swaminathan K. R., Mathur A. 1989; Proteinase-like activity in the cytotoxic factor produced by T-cell during dengue virus infection. Immunology 67:32–37
    [Google Scholar]
  14. Khanna M., Chaturvedi U. C., Sharma M., Pandey V. C., Mathur A. 1990; Increased capillary permeability mediated by dengue virus induced lymphokine. Immunology 69:449–454
    [Google Scholar]
  15. Khanna M., Chaturvedi U. C., Dhawan R., Tekwani B. L., Pandey V. C. 1991; Presence of Ca2+ is obligatory for the cytotoxic activity of dengue virus-induced cytotoxic factor. Immunology 72: (in press)
    [Google Scholar]
  16. Lowry O. H., Rosebrough N. J., Farr A. L., Randall R. J. 1951; Protein measurement with the Folin phenol reagent. Journal of Biological Chemistry 193:265–275
    [Google Scholar]
  17. Mohanty S., Ray A. K., Dey P. K. 1980; Cerebral oedema and blood-brain and blood-CSF barriers in experimental brain trauma: effect of indomethacin – a prostaglandin synthetase inhibitor. Indian Journal of Physiology and Pharmacology 24:91–96
    [Google Scholar]
  18. Myers R. M., Thiruvengadam K. V., Krishnaswamy S., Kalyanasundaram V., Jesudass E. S. 1969; Isolation of dengue type 2 from a child with encephalitis: cause or coincidence. Indian Journal of Medical Research 57:2030–2035
    [Google Scholar]
  19. Nathanson N., Cole G. A. 1970; Immunosuppression and experimental virus infection of the nervous system. Advances in Virus Research 16:397–428
    [Google Scholar]
  20. Reed L. J., Muench H. 1938; A simple method of estimating fifty percent endpoints. American Journal of Hygiene 27:493–497
    [Google Scholar]
  21. Sahaphong S., Riengrojpitak S., Bhamarapravati N., Chicachariyavej T. 1980; Electron microscopic study of the vascular endothelial cells in dengue haemorrhagic fever. Asian Journal of Tropical Medicine and Public Health 11:194
    [Google Scholar]
  22. Sarkar J. K., Mondal A., Chakaravarty S. K., Chatterjee S. N., Pal S. R. 1969; Isolation of dengue virus from the blood of a clinical case of encephalitis. Indian Journal of Medical Research 57:1616–1620
    [Google Scholar]
  23. Schlesinger R. W. 1981; General review of dengue and dengue haemorrhagic fever. In Proceedings of the First ICMR Seminar on Dengue Haemorrhagic Fever (1980, Kobe, Japan) pp 13–31 Edited by Hotta S. Kobe: International Centre for Medical Research, Kobe University School of Medicine;
    [Google Scholar]
  24. Shukla M. I., Chaturvedi U. C. 1981; Dengue virus-induced suppressor factor stimulates production of prostaglandin to mediate suppression. Journal of General Virology 56:241–249
    [Google Scholar]
  25. Sumarmo , Latu J, Suryaatmaja M, Nathin A. M. 1981; Studies of the liver function in dengue haemorrhagic fever. In Proceedings of the First ICMR Seminar on Dengue Haemorrhagic Fever (1980, Kobe, Japan) pp 191–201 Edited by Hotta S. Kobe: International Centre for Medical Research, Kobe University School of Medicine;
    [Google Scholar]
  26. Thumwood C. M., Hunt N. H., Clark I. A., Cowden W. B. 1988; Breakdown of the blood–brain barrier in murine cerebral malaria. Parasitology 96:579–589
    [Google Scholar]
  27. Vane J. R. 1976; Prostaglandins, as mediators of inflammation. Advances in Prostaglandin and Thromboxane Research 2:791
    [Google Scholar]
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