Demyelinating disorders of the central nervous system are among the most crippling neurological diseases affecting patients at various stages of life. In the most prominent demyelinating disease, multiple sclerosis, the regeneration of myelin sheaths often fails due to a default of the resident stem/precursor cells (oligodendrocyte precursor cells) to differentiate into mature myelin forming ce...

Chronic central nervous system demyelinating diseases result in long-term disability because of limited remyelination capacity and cumulative damage to axons. Corpus callosum demyelination in mice fed cuprizone provides a reproducible model of chronic demyelination in which the demyelinating agent can be removed to test modifications that promote recovery and to develop noninvasive neuroimaging...

Microglia and monocytes play important roles in regulating brain remyelination. We developed DUOC-01, a cell therapy product intended for treatment of demyelinating diseases, from banked human umbilical cord blood (CB) mononuclear cells. Immunodepletion and selection studies demonstrated that DUOC-01 cells are derived from CB CD14+ monocytes. We compared the ability of freshly isolated CB CD14+...

EBI2 receptor regulates the immune system, and in multiple, sclerosis is upregulated central nervous system infiltrating lymphocytes. In newborn EBI2-deficient mice, myelin development delayed, its persistent antagonism inhibits remyelination chemically demyelinated organotypic cerebellar slices. We used cuprizone model of multiple to elucidate role system-expressed de- remyelination. The wild-...

The class III POU-domain transcription factor SCIP/Oct-6 is expressed by promyelinating Schwann cells and, in tissue culture, by oligodendrocyte progenitors (OPs), but is down-regulated in both cells types as they differentiate. Although the expression of SCIP/Oct-6 has been examined in peripheral nerve remyelination, its expression in CNS remyelination has not been addressed. Using a toxin mod...

Myelin loss is a severe pathological hallmark common to a number of neurodegenerative diseases, including multiple sclerosis (MS). Demyelination in the central nervous system appears in the form of lesions affecting both white and gray matter structures. The functional consequences of demyelination on neuronal network and brain function are not well understood. Current therapeutic strategies fo...

In a recent paper published in J. Ex. Med, we provided evidence that the knockout of CX3CR1 blocked the clearance of myelin debris by microglia, which greatly affected the integrity of axons and myelin sheaths, preventing proper remyelination. These results highlight the crucial role played by CX3CR1 in myelin removal and show that there can be no efficient remyelination following a primary dem...

In demyelinating diseases such as multiple sclerosis, one of the treatment strategies includes remyelination using oligodendrocyte precursor cells (OPC). Catalpol, the extract of radix rehmanniae, is neuroprotective. Using an OPC culture model, we showed that 10 μM catalpol promotes OPC proliferation, cell migration and differentiation into mature oligodendrocytes. The 10 μM catalpol displayed ...

Myelin is essential for rapid and accurate conduction of electrical impulses by axons in the central and peripheral nervous system (PNS). Myelin is formed in the early postnatal period, and developmental myelination in the PNS depends on axonal signals provided by Nrg1/ErbB receptors. In addition, Nrg1 is required for effective nerve repair and remyelination in adulthood. We discuss here simila...

Remyelination is the regenerative response to demyelination. Although the oligodendrocyte progenitor is established as the major source of remyelinating cells, there is no conclusive evidence on whether mature, differentiated oligodendrocytes can also contribute to remyelination. Using two different inducible myelin-CreER mouse strains in which mature oligodendrocytes were prelabeled by the exp...