Understanding the molecular mechanism of blood-brain barrier damage in an experimental model of Japanese encephalitis: correlation with minocycline administration as a therapeutic agent - PubMed (original) (raw)

Understanding the molecular mechanism of blood-brain barrier damage in an experimental model of Japanese encephalitis: correlation with minocycline administration as a therapeutic agent

Manoj Kumar Mishra et al. Neurochem Int. 2009 Dec.

Abstract

The blood-brain barrier (BBB) serves to protect the central nervous system (CNS) from damage by exogenous molecules. Japanese encephalitis (JE), caused by a neurotropic flavivirus, leads to inflammation in the CNS, neuronal death and also compromises the structural and functional integrity of the BBB. Minocycline, a semisynthetic tetracycline, has been found to be broadly protective in neurological disease models featuring inflammation and cell death and at present, is being evaluated in clinical trials. In the present study, we propose that the neuroprotective role of minocycline in experimental models of JE extends also to the protection of the BBB. Damage to the BBB was assessed by Evan's blue dye exclusion test after minocycline treatment following Japanese encephalitis virus (JEV) infection. A breakdown of the BBB occurred in mice inoculated intravenously with JEV. This resulted in leakage of protein-bound Evan's blue dye into the brain tissue. Semi-quantitative RT-PCR revealed an up-regulation of chemokine receptors and adhesion molecules following JEV infection. Immunostaining showed leukocyte and neutrophil infiltration following JEV infection. Intraperitoneal injection of minocycline, beginning 24h post-JEV infection, abrogated the effects by reducing BBB damage, decreasing expression of iNOS, Cox-2, VEGF and also by reducing the elevated level of transcript of chemokine receptors and adhesion molecules in the brain. Matrix metalloproteinases (MMPs) are known to disrupt the BBB and minocycline was found to significantly decrease the activity of MMP-9 in brain tissue homogenates. Thus, minocycline, administered at a clinically relevant time, appears to maintain blood-brain barrier integrity following JEV infection.

PubMed Disclaimer

Cited by

Role of inflammatory cytokine burst in neuro-invasion of Japanese Encephalitis virus infection: an immunotherapeutic approaches.
Ahmad F, Ahmad S, Husain A, Pandey N, Khubaib M, Sharma R. Ahmad F, et al. J Neurovirol. 2024 Jun;30(3):251-265. doi: 10.1007/s13365-024-01212-z. Epub 2024 Jun 6. J Neurovirol. 2024. PMID: 38842651 Review.
Auraptene Has Antiviral Activity against Human Coronavirus OC43 in MRC-5 Cells.
Min JS, Jin YH, Kwon S. Min JS, et al. Nutrients. 2023 Jun 29;15(13):2960. doi: 10.3390/nu15132960. Nutrients. 2023. PMID: 37447286 Free PMC article.
Recent Advances in Antivirals for Japanese Encephalitis Virus.
Zhu Y, Chen S, Lurong Q, Qi Z. Zhu Y, et al. Viruses. 2023 Apr 23;15(5):1033. doi: 10.3390/v15051033. Viruses. 2023. PMID: 37243122 Free PMC article. Review.
Mice as an Animal Model for Japanese Encephalitis Virus Research: Mouse Susceptibility, Infection Route, and Viral Pathogenesis.
Frank JC, Song BH, Lee YM. Frank JC, et al. Pathogens. 2023 May 14;12(5):715. doi: 10.3390/pathogens12050715. Pathogens. 2023. PMID: 37242385 Free PMC article. Review.
Japanese Encephalitis Virus: An Update on the Potential Antivirals and Vaccines.
Srivastava KS, Jeswani V, Pal N, Bohra B, Vishwakarma V, Bapat AA, Patnaik YP, Khanna N, Shukla R. Srivastava KS, et al. Vaccines (Basel). 2023 Mar 27;11(4):742. doi: 10.3390/vaccines11040742. Vaccines (Basel). 2023. PMID: 37112654 Free PMC article. Review.

Understanding the molecular mechanism of blood-brain barrier damage in an experimental model of Japanese encephalitis: correlation with minocycline administration as a therapeutic agent - PubMed (original) (raw)