Exogenous schwann cells migrate, remyelinate and promote clinical recovery in experimental auto-immune encephalomyelitis

Schwann cell (SC) transplantation is currently being discussed as a strategy that may promote functional recovery in patients with multiple sclerosis (MS) and other inflammatory demyelinating diseases of the central nervous system (CNS). However this assumes they will not only survive but also remyelinate demyelinated axons in the chronically inflamed CNS. To address this question we investigated the fate of transplanted SCs in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) in the Dark Agouti rat; an animal model that reproduces the complex inflammatory demyelinating immunopathology of MS. We now report that SCs expressing green fluorescent protein (GFP-SCs) allografted after disease onset not only survive but also migrate to remyelinate lesions in the inflamed CNS. GFP-SCs were detected more frequently in the parenchyma after direct injection into the spinal cord, than via intra-thecal delivery into the cerebrospinal fluid. In both cases the transplanted cells intermingled with astrocytes in demyelinated lesions, aligned with axons and by twenty one days post transplantation had formed Pzero protein immunoreactive internodes. Strikingly, GFP-SCs transplantation was associated with marked decrease in clinical disease severity in terms of mortality; all GFP-SCs transplanted animals survived whilst 80% of controls died within 40 days of disease

Slit1 Protein Regulates SVZ-Derived Precursor Mobilization in the Adult Demyelinated CNS

International audienceSlit1 is a secreted axon guidance molecule, also involved in adult neurogenesis. In physiological conditions, Slit1 loss promotes ectopic dispersal of SVZ-derived neural precursors (SVZ-NPCs) into periventricular structures such as the corpus callosum. Demyelination of the corpus callosum triggers SVZ-NPC migration to ectopic locations and their recruitment by the lesion, suggesting a possible role for Slit1 in SVZ-NPCs ectopic dispersal regulation in pathological conditions. Here, we have investigated the function of Slit1 protein in the recruitment of SVZ-NPCs after CNS demyelination. We find that the dynamics of oligodendrogenesis and temporal profile of developmental myelination in Slit1 -/- mice are similar to Slit1 +/- controls. SVZ micro-dissection and RT-PCR from wild-type mice, show that Slits and Robos are physiologically regulated at the transcriptional level in response to corpus callosum demyelination suggesting their role in the process of SVZ-NPC ectopic migration in demyelinating conditions. Moreover, we find that the number of SVZ-NPCs recruited by the lesion increases in Sli1-/- mice compared to Slit1 +/- mice, leading to higher numbers of Olig2+ cells within the lesion. Time-lapse video-microscopy of immuno-purified NPCs shows that Slit1-deficient cells migrate faster and make more frequent directional changes than control NPCs, supporting a cell-autonomous mechanism of action of Slit1 in NPC migration. In conclusion, while Slit1 does not affect the normal developmental process of oligodendrogenesis and myelination, it regulates adult SVZ-NPC ectopic migration in response to demyelination, and consequently oligodendrocyte renewal within the lesion

A hydrologic tracer study in a small, natural wetland in the humid tropics of Costa Rica

Growing populations and food demand in the tropics are leading to increased environmental pressures on wetland ecosystems, including a greater reliance on natural wetlands for water quality improvement. Effective assessment of wetland treatment potential requires an improved understanding of the hydraulic and biogeochemical factors that govern contaminant behavior, however detailed studies of flow through natural, tropical wetlands are scarce. We performed a tracer study using a conservative salt (potassium bromide) to examine the hydraulic behavior of a small, natural wetland in the Costa Rican humid tropics and modeled observed breakthrough curves using the 1-D advection-dispersion equation. Velocities in the wetland were extremely slow, from less than 4 m day(-1) to a maximum of similar to 30 m day(-1), and were distributed across several flowpaths, illustrating a spatial heterogeneity of flow and velocities. Modeled dispersion coefficients were also low (33 +/- A 33 m(2) day(-1)). Estimated residence times suggested high potential pollutant removal capacity over a range of influent concentrations, reinforcing the environmental services provided by this and other small tropical wetlands. The study also highlighted how small variations in wetland topography and vegetation yield strong differences in transport patterns that affect transport and mixing in densely vegetated, heterogeneous wetland systems. Empirical data on the hydraulics, and resulting ecosystem functions, of small, distributed wetlands may provide support for improved conservation and management of these important ecosystems

Myelin oligodendrocyte glycoprotein is expressed in the peripheral nervous system of rodents and primates

The myelin oligodendrocyte glycoprotein (MOG) is a minor CNS myelin-specific protein that is an important candidate autoantigen in multiple sclerosis. We now report that MOG mRNA transcripts are present in the peripheral nervous system of rodents and primates at levels approximately ten-fold lower than in brain as demonstrated by real time PCR. A major source of this signal are Schwann cells which are also shown to express MOG protein within their cytoplasm in vitro by immunohistochemistry. Expression of MOG by Schwann cells associated with tissue innervation may account for the widespread distribution of low levels of MOG mRNA transcripts, and potentially may provide a source of antigen that can influence the composition and function of the MOG-specific immune repertoire. (C) 2003 Elsevier Ireland. All rights reserved