Skip to main content

Advertisement

SpringerLink
Log in

Free Radical Generation by Neurons in Rat Model of Japanese Encephalitis

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Increased generation of free radicals resulting in brain injury is a feature of many viral infections. The present study has been undertaken to evaluate the level of free radicals in Japanese encephalitis. Twelve days old Wistar rats were inoculated intracerebrally with 3 × 106 pfu of JE virus and were sacrificed on 3, 6, 10, and 20 days post inoculation (dpi). The neuronal levels of reactive oxygen species (ROS), nitric oxide (NO), peroxinitrite (OONO−), necrotic and apoptotic cell population were estimated by flow cytometry. Hematoxylin-eosin staining was also performed. Maximum level of neuronal ROS and OONO− was observed on 6 dpi; however, NO levels peaked on 10 dpi. Free radical generation significantly declined on 20 dpi as compared to control. Apoptotic cell death gradually increased over the time. Neuronal shrinkage and necrosis was also observed. The results of our study indicate that free radicals increased in acute JE and declined at later stage, which may contribute to cell death.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Tsai TF (1998) New initiatives for the control of Japanese encephalitis by vaccination: minutes of a WHO/CVI meeting, Bangkok, Thailand. Vaccine 18:1–25. doi:10.1016/S0264-410X(00)00037-2

    Article  Google Scholar 

  2. Misra UK, Kalita J, Kumar S et al (1994) Radiological and neurophysiological changes in Japanese encephalitis. J Neurol Neurosurg Psychiatry 57:1484–1487. doi:10.1136/jnnp.57.12.1484

    Article  CAS  PubMed  Google Scholar 

  3. Kalita J, Misra UK, Pandey S et al (2003) A comparison of clinical and radiological findings in adults and children with Japanese encephalitis. Arch Neurol 60:1760–1764. doi:10.1001/archneur.60.12.1760

    Article  CAS  PubMed  Google Scholar 

  4. Ghoshal A, Das S, Ghosh S et al (2007) Proinflammatory mediators released by activated microglia induces neuronal death in Japanese encephalitis. Glia 55:483–496. doi:10.1002/glia.20474

    Article  PubMed  Google Scholar 

  5. Valyi-Nagy T, Dermody TS (2005) Role of oxidative damage in the pathogenesis of viral infections of the nervous system. Histol Histopathol 20:957–967

    CAS  PubMed  Google Scholar 

  6. Palu G, Biasolo MA, Sartor G (1994) Effects of herpes simplex virus type 1 infection on the plasma membrane and related functions of HeLa S3 cells. J Gen Virol 75:3337–3344. doi:10.1099/0022-1317-75-12-3337

    Article  CAS  PubMed  Google Scholar 

  7. Akaike T (2001) Role of free radicals in viral pathogenesis and mutation. Rev Med Virol 11:87–101. doi:10.1002/rmv.303

    Article  CAS  PubMed  Google Scholar 

  8. Bukrinsky MI, Nottet HS, Schmidtmayerova H et al (1995) Regulation of nitric oxide synthase activity in human immunodeficiency virus type 1 (HIV-1)-infected monocytes: implications for HIV-associated neurological disease. J Exp Med 181:735–745. doi:10.1084/jem.181.2.735

    Article  CAS  PubMed  Google Scholar 

  9. Swarup V, Das S, Ghosh S et al (2007) Tumor necrosis factor receptor-1-induced neuronal death by TRADD contributes to the pathogenesis of Japanese encephalitis. J Neurochem 103:771–783. doi:10.1111/j.1471-4159.2007.04790.x

    Article  CAS  PubMed  Google Scholar 

  10. Hase T, Dubois DR, Summers PL (1990) Comparative study of mouse brains infected with Japanese encephalitis virus by intracerebral or intraperitoneal inoculation. Int J Exp Pathol 71:857–869

    CAS  PubMed  Google Scholar 

  11. Ogata A, Nagashima K, Hall WW et al (1991) Japanese encephalitis virus neurotropism is dependent on the degree of neuronal maturity. J Virol 65:880–886

    CAS  PubMed  Google Scholar 

  12. Oyama Y, Carpenter DO, Chikahisa L et al (1996) Flow cytometric estimation on glutamate and kainate induced increases in intracellular Ca2+ of brain neurons: a technical aspect. Brain Res 728:121–124. doi:10.1016/0006-8993(96)00504-5

    Article  CAS  PubMed  Google Scholar 

  13. Srivastava AK, Kalita J, Dohare P et al (2009) Studies of free radical generation by neurons in a rat model of cerebral venous sinus thrombosis. Neurosci Lett 450:127–131. doi:10.1016/j.neulet.2008.11.036

    Article  CAS  PubMed  Google Scholar 

  14. Kooy NW, Royall JA, Ischiropoulos H et al (1994) Peroxynitrite-mediated oxidation of dihydrorhodamine 123. Free Radic Biol Med 16:149–156. doi:10.1016/0891-5849(94)90138-4

    Article  CAS  PubMed  Google Scholar 

  15. Swarup V, Ghosh J, Mishra MK et al (2008) Novel strategy for treatment of Japanese encephalitis using arctigenin, a plant lignan. J Antimicrob Chemother 61:679–688. doi:10.1093/jac/dkm503

    Article  CAS  PubMed  Google Scholar 

  16. Zimmerman HM (1945) The pathology of Japanese B encephalitis. Am J Pathol 22:965–991

    Google Scholar 

  17. Shankar SK, Rao TV, Mruthyunjayanna BP et al (1983) Autopsy study of brains during an epidemic of Japanese encephalitis in Karnataka. Indian J Med Res 78:431–440

    CAS  PubMed  Google Scholar 

  18. Lopez-Guerrero JA, Alonso MA (1997) Nitric oxide production induced by herpes simplex virus type 1 does not alter the course of the infection in human monocytic cells. J Gen Virol 78:1977–1980

    CAS  PubMed  Google Scholar 

  19. Badwey JA, Karnovsky ML (1980) Active oxygen species and the functions of phagocytic leukocytes. Annu Rev Biochem 49:695–726. doi:10.1146/annurev.bi.49.070180.003403

    Article  CAS  PubMed  Google Scholar 

  20. Leib SL, Kim YS, Chow LL et al (1996) Reactive oxygen intermediates contribute to necrotic and apoptotic neuronal injury in an infant rat model of bacterial meningitis due to group B streptococci. J Clin Invest 98:2632–2639. doi:10.1172/JCI119084

    Article  CAS  PubMed  Google Scholar 

  21. Moncada S, Higgs A (1993) The l-arginine-nitric oxide pathway. N Engl J Med 329:2002–2012. doi:10.1056/NEJM199312303292706

    Article  CAS  PubMed  Google Scholar 

  22. Stuehr DJ, Griffith OW (1992) Mammalian nitric oxide synthases. Adv Enzymol Relat Areas Mol Biol 65:287–346. doi:10.1002/9780470123119.ch8

    Article  CAS  PubMed  Google Scholar 

  23. Palomba L, Amadori A, Cantoni O (2007) Early release of arachidonic acid prevents an otherwise immediate formation of toxic levels of peroxynitrite in astrocytes stimulated with lipopolysaccharide/interferon-gamma. J Neurochem 103:904–913. doi:10.1111/j.1471-4159.2007.04793.x

    Article  CAS  PubMed  Google Scholar 

  24. Lee CJ, Liao CL, Lin YL (2005) Flavivirus activates phosphatidylinositol 3-kinase signaling to block caspase-dependent apoptotic cell death at the early stage of virus infection. J Virol 79:8388–8399. doi:10.1128/JVI.79.13.8388-8399.2005

    Article  CAS  PubMed  Google Scholar 

  25. Kamat CD, Gadal S, Mhatre M et al (2008) Antioxidants in central nervous system diseases: preclinical promise and translational challenges. J Alzheimers Dis 15:473–493

    CAS  PubMed  Google Scholar 

  26. Boillee S, Cleveland DW (2008) Revisiting oxidative damage in ALS: microglia, Nox, and mutant SOD1. J Clin Invest 118:474–478

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Authors acknowledge the Indian Council of Medical Research, New Delhi for financial support to Ruchi Srivastava as Senior Research Fellow.

Author information

Authors and Affiliations

  1. Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareily Road, Lucknow, 226014, Uttar Pradesh, India

    Ruchi Srivastava, Jayantee Kalita & Usha Kant Misra

  2. Department of Biotechnology, Babasaheb Bhimrao Ambedkar University, Lucknow, India

    Mohammad Yahiya Khan

Authors
  1. Ruchi Srivastava
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jayantee Kalita
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mohammad Yahiya Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Usha Kant Misra
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Usha Kant Misra.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Srivastava, R., Kalita, J., Khan, M.Y. et al. Free Radical Generation by Neurons in Rat Model of Japanese Encephalitis. Neurochem Res 34, 2141–2146 (2009). https://doi.org/10.1007/s11064-009-0008-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-009-0008-7

Keywords

Search

Navigation