Lower Richness of Small Wild Mammal Species and Chagas Disease Risk

A new epidemiological scenario involving the oral transmission of Chagas disease, mainly in the Amazon basin, requires innovative control measures. Geospatial analyses of the Trypanosoma cruzi transmission cycle in the wild mammals have been scarce. We applied interpolation and map algebra methods to evaluate mammalian fauna variables related to small wild mammals and the T. cruzi infection pattern in dogs to identify hotspot areas of transmission. We also evaluated the use of dogs as sentinels of epidemiological risk of Chagas disease. Dogs (n = 649) were examined by two parasitological and three distinct serological assays. kDNA amplification was performed in patent infections, although the infection was mainly sub-patent in dogs. The distribution of T. cruzi infection in dogs was not homogeneous, ranging from 11–89% in different localities. The interpolation method and map algebra were employed to test the associations between the lower richness in mammal species and the risk of exposure of dogs to T. cruzi infection. Geospatial analysis indicated that the reduction of the mammal fauna (richness and abundance) was associated with higher parasitemia in small wild mammals and higher exposure of dogs to infection. A Generalized Linear Model (GLM) demonstrated that species richness and positive hemocultures in wild mammals were associated with T. cruzi infection in dogs. Domestic canine infection rates differed significantly between areas with and without Chagas disease outbreaks (Chi-squared test). Geospatial analysis by interpolation and map algebra methods proved to be a powerful tool in the evaluation of areas of T. cruzi transmission. Dog infection was shown to not only be an efficient indicator of reduction of wild mammalian fauna richness but to also act as a signal for the presence of small wild mammals with high parasitemia. The lower richness of small mammal species is discussed as a risk factor for the re-emergence of Chagas disease

Cisterna Magna Injection in Rats to Study Glymphatic Function

The recently discovered glymphatic system, which supports brain-wide clearance of metabolic waste, has become the subject of intense research within the past few years. Its nomenclature arose due to its functionally analogous nature to the lymphatic system in combination with glial cells that are part of its anatomical boundaries. The influx of cerebrospinal fluid (CSF) from perivascular spaces into the brain interstitium acts to clear intraparenchymal solutes. CSF is produced by the choroid plexus and flows from the ventricles to the subarachnoid space via the cisterna magna, and as such the injection of tracer molecules into any one of these spaces could be used for studying CSF movement through the glymphatic system. Of these options, the cisterna magna is most favorable as it offers a route of entry that does not involve craniotomy. Herein we describe the cisterna magna (CM) injection procedure carried out in rats, essential for studying glymphatic influx and efflux dynamics

Physiological blood–brain transport is impaired with age by a shift in transcytosis

The vascular interface of the brain, known as the blood-brain barrier (BBB), is understood to maintain brain function in part via its low transcellular permeability1-3. Yet, recent studies have demonstrated that brain ageing is sensitive to circulatory proteins4,5. Thus, it is unclear whether permeability to individually injected exogenous tracers-as is standard in BBB studies-fully represents blood-to-brain transport. Here we label hundreds of proteins constituting the mouse blood plasma proteome, and upon their systemic administration, study the BBB with its physiological ligand. We find that plasma proteins readily permeate the healthy brain parenchyma, with transport maintained by BBB-specific transcriptional programmes. Unlike IgG antibody, plasma protein uptake diminishes in the aged brain, driven by an age-related shift in transport from ligand-specific receptor-mediated to non-specific caveolar transcytosis. This age-related shift occurs alongside a specific loss of pericyte coverage. Pharmacological inhibition of the age-upregulated phosphatase ALPL, a predicted negative regulator of transport, enhances brain uptake of therapeutically relevant transferrin, transferrin receptor antibody and plasma. These findings reveal the extent of physiological protein transcytosis to the healthy brain, a mechanism of widespread BBB dysfunction with age and a strategy for enhanced drug delivery