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Temporal expression of inflammatory mediators in brain basilar artery vasculitis and cerebrospinal fluid of rabbits with coccidioidal meningitis.

Zucker KE, Kamberi P, Sobel RA, Cloud G, Meli DN, Clemons KV, Stevens DA, Williams PL, Leib SL

Dept. of Laboratory Medicine (SC-12), Children's Hospital Central California, 9300 Valley Children's Place, Madera, CA 93638-8762, USA. kzucker@childrenscentralcal.org

Strokes due to transmural vasculitis associated with coccidioidal meningitis result in significant morbidity and mortality. The immunological and inflammatory processes responsible are poorly understood. To determine the inflammatory mediators, i.e. cytokines, chemokines, iNOS, matrix metalloproteinase-9 (MMP-9), that possibly contribute to vasculitis, temporal mRNA expression in brain basilar artery samples and MMP-9 protein in the CSF of male NZW rabbits infected intracisternally with 6.5 x 10(4) arthroconidia of Coccidioides immitis were assessed. Five infected and 3 sham-injected rabbits at each time point were euthanized 4, 9, 14 and 20 days post infection. All infected rabbits had neurological abnormalities and severe vasculitis in the basilar arteries on days 9-20. In basilar arteries of infected animals versus controls, mRNAs encoding for IL-6, iNOS, IFN-gamma, IL-2, MCP-1, IL-1beta, IL-10, TNF-alpha, CCR-1, MMP-9, TGF-beta, as well as MMP-9 protein in CSF, were found to be significantly up-regulated. Thus, this study identified inflammatory mediators associated with CNS vasculitis and meningitis due to C. immitis infection. Assessment of the individual contribution of each mediator to vasculitis may offer novel approaches to the treatment of coccidioidal CNS infection. This study also provides unique methodology for immunology studies in a rabbit model.

Published 20 February 2006 in Clin Exp Immunol, 143(3): 458-66.
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Meningitis Research Today Archive:

Volume 1 (2004)
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Volume 2 (2005)
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Meningitis Books

Neonatal Meningitis (Clinics in Developmental Medicine (Mac Keith Press))

Neonatal Meningitis (Clinics in Developmental Medicine (Mac Keith Press))