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The use of progenitors and stem cells for neural grafting is promising, as these not only have the potential to be maintained in vitro until use, but may also prove less likely to evoke an immunogenic response in the host, when compared to primary (fetal) grafts. We investigated whether the short-term survival of a grafted conditionally immortalised murine neuroepithelial stem cell line (MHP36) (2 weeks post-implantation, 4 weeks post-ischaemia) is influenced by: (i) immunosuppression (cyclosporin A (CSA) vs. no CSA), (ii) the local (intact vs. lesioned hemisphere), or (iii) global (lesioned vs. sham) brain environment. MHP36 cells were transplanted ipsi- and contralateral to the lesion in rats with middle cerebral artery occlusion (MCAo) or sham controls. Animals were either administered CSA or received no immunosuppressive treatment. A proliferation assay of lymphocytes dissociated from cervical lymph nodes, grading of the survival of the grafted cells, and histological evaluation of the immune response revealed no significant difference between animals treated with or without CSA. There was no difference in survival or immunological response to cells grafted ipsi- or contralateral to the lesion. Although a local upregulation of immunological markers (MHC class I, MHC class II, CD45, CD11b) was detected around the injection site and the ischaemic lesion, these were not specifically upregulated in response to transplanted cells. These results provide evidence for the low immunogenic properties of MHP36 cells during the initial period following implantation, known to be associated with an acute host immune response and ensuing graft rejection. [Copyright &y& Elsevier]

Abstract: Microglia, the CNS resident macrophages, and astrocytes, the most abundant glial cell population, are both implicated in brain pathologies and can exhibit a pro-inflammatory phenotype. Microglial cells are known to rapidly and strongly react to brain insults. They will promote astrocyte activation and may lead to a vicious, self-perpetuating cycle of chronic inflammation. To obtain a better understanding of the individual role of both cell types, primary cells are frequently used in in vitro studies, but the purity of specific cell cultures remains rarely investigated. The aim of this study is to determine the effect of specific removal of microglial cells on the inflammatory properties of different glial cultures. Here, the removal of microglial contamination from mixed glial cultures to obtain astrocyte-enriched cultures was achieved using a magnetic cell sorting approach. Compared to mixed cultures, we clearly showed that these enriched cultures are only weakly activated by pro-inflammatory agents (lipopolysaccharide, interferon-γ or beta-amyloid peptide). This finding was confirmed using twice-sorted astrocyte-enriched cultures and microglia-free cultures composed of neurosphere-derived astrocytes. Thus, we present evidence that the magnitude of the pro-inflammatory response is linked to the percentage of microglia in cultures. Due to their high reactivity to various insults or pro-inflammatory stimuli, microglia-derived effects could be credited to astrocytes in mixed glial cultures. Therefore, we highlight the importance of monitoring the presence of microglia in glial cultures since they can affect the interpretation of the results, especially when inflammatory processes are studied. [Copyright &y& Elsevier]

Abstract: The synthesis of resveratrol fatty alcohols (RFAs), a new class of small molecules presenting strong potential for the treatment of neurological diseases, is described. RFAs, hybrid compounds combining the resveratrol nucleus and ω-alkanol side chains, are able to modulate neuroinflammation and to induce differentiation of neural stem cells into mature neurons. Acting on neuroprotection and neuroregeneration, RFAs represent an innovative approach for the treatment or cure of neuropathies. [Copyright &y& Elsevier]

Abstract: The synthesis of tocopherol fatty alcohols (TFAs), potent microglial activation modulators, was achieved via C-alkylation of trimethylhydroquinone. Several analogs, in particular water-soluble prodrugs, have been synthesized using a Wittig reaction and their antioxidant activities have been evaluated. [Copyright &y& Elsevier]