Oligodendrocytes (OLs) are the myelinating cells of the central nervous system (CNS) during development and throughout adulthood. They result from a complex and well controlled process of activation, proliferation, migration and differentiation of oligodendrocyte progenitor cells (OPCs) from the germinative niches of the CNS. In multiple sclerosis (MS), the complex pathological process produces dysfunction and apoptosis of OLs leading to demyelination and neurodegeneration. This review attempts to describe the patterns of demyelination in MS, the steps involved in oligodendrogenesis and myelination in healthy CNS, the different pathways leading to OLs and myelin loss in MS, as well as principles involved in restoration of myelin sheaths. Environmental factors and their impact on OLs and pathological mechanisms of MS are also discussed. Finally, we will present evidence about the potential therapeutic targets in re-myelination processes that can be accessed in order to develop regenerative therapies for MS.
Hematopoietic cell transplantation (HCT) is widely performed for neoplastic and non-neoplastic diseases. HCT involves intravenous infusion of hematopoietic progenitor cells from human leukocyte antigen (HLA)-matched donor (allogeneic) or from the patient (autologous). Before HCT, the patient is prepared with high dose chemotherapy and/or radiotherapy to destroy residual malignant cells and to reduce immunologic resistance. After HCT, chemotherapy is used to prevent graft rejection and graft versus host disease (GvHD). Neurological complications are related to the type of HCT, underlying disease, toxicity of the conditioning regimens, immunosuppression caused by conditioning regimens, vascular complications generated by thrombocytopenia and/or coagulopathy, GvHD and inappropriate immune response. In this review, neurological complications are presented according to time of onset after HCT: (1) early complications (in the first month) - related to harvesting of stem cells, during conditioning (drug toxicity, posterior reversible encephalopathy syndrome), related to pancytopenia, (2) intermediate phase complications (second to sixth month) - central nervous system infections caused by prolonged neutropenia and progressive multifocal leukoencephalopathy due to JC virus, (3) late phase complications (after sixth month) - neurological complications of GvHD, second neoplasms and relapses of the original disease.
Oligodencrocytes (OLs) are the main glial cells of the central nervous system involved in myelination of axons. In multiple sclerosis (MS), there is an imbalance between demyelination and remyelination processes, the last one performed by oligodendrocyte progenitor cells (OPCs) and OLs, resulting into a permanent demyelination, axonal damage and neuronal loss. In MS lesions, astrocytes and microglias play an important part in permeabilization of blood-brain barrier and initiation of OPCs proliferation. Migration and differentiation of OPCs are influenced by various factors and the process is finalized by insufficient acummulation of OLs into the MS lesion. In relation to all these processes, the author will discuss the potential targets for remyelination strategies.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.