title: Microenvironmental regulation of oligodendrocyte replacement and remyelination in spinal cord injury.
abstract: Myelin is a proteolipid sheath enwrapping axons in the nervous system that facilitates signal transduction along the axons. In the central nervous system (CNS), oligodendrocytes are specialized glial cells responsible for myelin formation and maintenance. Following spinal cord injury (SCI), oligodendroglia cell death and myelin damage (demyelination) cause chronic axonal damage and irreparable loss of sensory and motor functions. Accumulating evidence shows that replacement of damaged oligodendrocytes and renewal of myelin (remyelination) are promising approaches to prevent axonal degeneration and restore function following SCI. Neural precursor cells (NPCs) and oligodendrocyte progenitor cells (OPCs) are two main resident cell populations in the spinal cord with innate capacities to foster endogenous oligodendrocyte replacement and remyelination. However, due to the hostile microenvironment of SCI, the regenerative capacity of these endogenous precursor cells is conspicuously restricted. Activated resident glia, along with infiltrating immune cells, are among the key modulators of secondary injury mechanisms that create a milieu impermissible to oligodendrocyte differentiation and remyelination. Recent studies have uncovered inhibitory roles for astrocyte-associated molecules such as matrix chondroitin sulfate proteoglycans (CSPGs), and a plethora of pro-inflammatory cytokines and neurotoxic factors produced by activated microglia/macrophages. The quality of axonal remyelination is additionally challenged by dysregulation of the supportive growth factors required for maturation of new oligodendrocytes and axo-oligodendrocyte signalling. Careful understanding of factors that modulate the activity of endogenous precursor cells in the injury microenvironment is a key step in developing efficient repair strategies for remyelination and functional recovery following SCI.
authors: Regenerative Medicine Program, Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors: Arsalan
authors: A
authors: Alizadeh
authors: Regenerative Medicine Program, Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors: Soheila
authors: S
authors: Karimi-Abdolrezaee
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D009186:Myelin Sheath / Q000502:physiology*; D009836:Oligodendroglia / Q000166:cytology / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D013234:Stem Cells / Q000502:physiology