In mice, the generation of a surprisingly large numbers of OLs occurs even in adulthood, which contribute towards a distinct remodeling of the myelin sheath and remyelination after CNS injury ( Powers et al., 2013 Young et al., 2013). CNS myelination begins prenatally and proceeds gradually at the level of axonal tracts in a rostral to caudal-dorsal to ventral gradient ( Schreyer and Jones, 1982 Almeida et al., 2011 Wang and Young, 2014). OPCs, activated by specific mitogens, and differentiating factors proliferate and progress through a pre-myelinating phase to eventually become myelinating OLs ( Boulanger and Messier, 2014).

In the CNS, the renewal of myelinating OLs comes from oligodendrocyte precursor cells (OPCs). OLs represent almost 75% of the neocortical glial population, and each OL is capable of laying down myelin on 40–60 short axonal segments of multiple CNS axons with varying diameter ( Matthews and Duncan, 1971 Lubetzki et al., 1993 Shaham, 2006 Pelvig et al., 2008 Fields et al., 2015). Formation of the myelin sheath occurs in an outside to inside fashion by a process involving homotypic fusion of myelinophore organelles within the confines of their processes ( Ioannidou et al., 2012 Snaidero et al., 2014 Szuchet et al., 2015). In the case of OLs, they extend their processes spirally inward, around the axons, in a corkscrew-like manner to lay down a multi-lamellar, compact, lipid rich sheath (myelin sheath myelin from myelós, Greek for marrow) on the axons. Oligodendrocytes (OLs) in the central nervous system (CNS) and Schwann cells (SCs) in the peripheral nervous system (PNS) ensheathe axons with myelin for the promotion of saltatory conduction ( Nave and Werner, 2014). Neuron-glia interactions have been fundamental to the structure and function of the brain throughout evolution ( Herculano-Houzel, 2014). Here, we examine the intersection between intracellular signaling pathways in neurons and glia that are involved in axon myelination and axon growth, to provide greater insight into how interrogating this complex network of molecular interactions may lead to new therapeutics targeting SCI. However, less attention has been placed on how the myelination of the axon after SCI, whether by endogenous glia or exogenously implanted glia, may alter axon regeneration. These studies have employed antagonizing antibodies and knockout animals to examine how the growth cone of the re-growing axon responds to the presence of myelin and myelin-associated inhibitors (MAIs) within the lesion environment and caudal spinal cord. Here, the role of myelin, both intact and debris, in antagonizing axon regeneration has been the focus of numerous investigations. Insufficient RAG expression in the injured neuron and the presence of inhibitory ECM at the lesion, leads to structural alterations in the axon that perturb the growth machinery, or form an extraneous barrier to axonal regeneration, respectively. Carter Department of Veterans Affairs Medical Center, Miami, FL, USAįollowing spinal cord injury (SCI), a multitude of intrinsic and extrinsic factors adversely affect the gene programs that govern the expression of regeneration-associated genes (RAGs) and the production of a diversity of extracellular matrix molecules (ECM). 4The Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA.3The Neuroscience Program, University of Miami Miller School of Medicine, Miami, FL, USA.

2The Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, USA.

1The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, USA.

Prota lyn review