Authors

J Rodgers³; B Bradley¹; P Montague¹; M P Barrett²; P G Kennedy¹;  ¹ Institute of Infection Immunity and Inflammation, University of Glasgow;  ² Institute of Infection Immunity and Inflammation, Wellcome Centre for Molecular Parasitology, University of Glasgow;  ³ Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow

Discussion

This study uses the well characterised T.b.brucei GVR35 CD-1 murine model of trypanosome infection to investigate the CNS-response associated with the disease. At 7, 14, 21 and 28 days post-infection we assessed; the severity of the neuropathological reaction, the parasite load within the brain using Taqman PCR analysis and gene transcription using an Illumina mouse WG6 microarray. Contrast enhanced magnetic resonance imaging was also performed at each time point to evaluate BBB integrity. The results show progressive increases in the severity of the neuropathological reaction, parasite load within the CNS and BBB impairment as the disease advances. In each case, significant (P<0.01) increases were detected in animals at 14 days post-infection. In this model, late-stage infections are not patent until day 21 post-infection. During the CNS-stage of the disease microarray analysis detected changes in the expression of over 300 genes associated with KEGG pathways predominately related to the immune response. In addition, metabolomics analysis of CSF and plasma demonstrated alterations in the levels of several metabolites in samples taken 21 days following infection. Precise targeted studies are now required to enhance further our knowledge of the pathogenesis of this and other CNS-inflammatory conditions.