Multiple sclerosis (MS) is a chronic neuroinflammatory disorder of the central nervous system (CNS) that usually presents in young adults and predominantly in females. Microglia, a major resident immune cell in the CNS, are critical players in both CNS homeostasis and disease. We have previously demonstrated that microglia can be efficiently depleted by the administration of tamoxifen in mice, with ensuing repopulation deriving from both the proliferation of residual CNS resident microglia and the engraftment of peripheral monocyte-derived microglia-like cells.
View Article and Find Full Text PDFLong-term survival and integration of neural progenitor cells (NPCs) transplanted following spinal cord injury (SCI) have been observed. However, questions concerning the differentiation choice, the mechanism of action, and the contribution of NPCs to functional recovery remains unanswered. Therefore, we investigated the differentiation of NPCs, global transcriptomal changes in transplanted NPCs, the effect of NPCs on neuroinflammation, and the causality between NPC transplantation and functional recovery.
View Article and Find Full Text PDFBackground: Mesenchymal stem cells (MSCs) and their cellular response to various stimuli have been characterized in great detail in culture conditions. In contrast, the cellular response of MSCs in an in vivo setting is still uncharted territory. In this study, we investigated the cellular response of MSCs following transplantation into spinal cord injury (SCI).
View Article and Find Full Text PDFStudies in multiple sclerosis have demonstrated that normal-appearing white matter can harbor pathological changes. Here we investigated the effects of neuroinflammation, modeled by experimental autoimmune encephalomyelitis (EAE) on neural stem/progenitor cells (NPCs) located distally to inflammatory foci. We observed that EAE-derived NPCs had a lower capacity to differentiate into oligodendrocytes and an increased neuronal differentiation than control NPCs.
View Article and Find Full Text PDFBackground: It is well documented that bone marrow-derived cells can fuse with a diverse range of cells, including brain cells, under normal or pathological conditions. Inflammation leads to robust fusion of bone marrow-derived cells with Purkinje cells and the formation of binucleate heterokaryons in the cerebellum. Heterokaryons form through the fusion of two developmentally differential cells and as a result contain two distinct nuclei without subsequent nuclear or chromosome loss.
View Article and Find Full Text PDFHydrogen peroxide (H2O2) is a reactive oxygen species that is involved in immunity and neuroinflammation. Here, we investigated whether and how pathophysiological levels of H2O2 influenced the differentiation of neural progenitor cells (NPCs). H2O2 levels within the range measured at neuroinflammatory events were applied to rat primary NPC cultures during 24 h, and effects were assessed directly after exposure or in NPCs that were differentiated for 7 days after H2O2 removal.
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