This chapter provides an overview of the efficacy of Schwann cell (SC) and olfactory ensheathing cell (OEC) transplantation to repair the central nervous system (CNS). Remyelination of CNS axons by SCs has been observed in many studies of experimentally induced and naturally occurring pathologic processes. Axons are remyelinated by either endogenous SCs that have migrated into the demyelinated site or by transplanted SCs. Restoration of conduction properties has been studied following remyelination by transplanted SCs. Using the microtransplantation technique to minimize disturbance of the tract architecture, cultured SCs placed into either the cervical corticospinal or ascending dorsal column tracts cause sprouting of both types of axons. A combination strategy involved the transplantation of OECs into the stumps beside the SC bridge after complete transaction. Although OECs do not normally form myelin in the olfactory system, numerous studies have demonstrated that SC-like myelin is produced following the transplantation of OECs.

This chapter provides an overview of molecular mechanisms that guide axon extension during neural development. It introduces the growth cone, a specialized motile structure at the tip of the axon responsible for sensing and responding to guidance cues. Growth cone morphology is a direct consequence of the organization of the two main components of its cytoskeleton, microtubules, and filamentous actin. The chapter describes the trajectory of embryonic spinal commissural axons, and reviews axonal guidance cues. It presents a description of the growing understanding of the cellular and molecular mechanisms that transduce extracellular guidance cues into directed axon growth. As an axon extends along its trajectory, its growth cone has the capacity to change its response to local guidance cues. The chapter concludes with a discussion on the possibility that cues now known to regulate axon guidance during development may subsequently influence axon regeneration in the adult central nervous system (CNS).

This chapter discusses the environment of the glial scar, with particular focus on the role of chondroitin sulfate proteoglycans (CSPGs) in regeneration failure. Many injuries of the central nervous system (CNS) occur with an accompanying opening of the blood-brain barrier. Non-CNS molecules entering the brain parenchyma through the disrupted blood-brain barrier have significant effects on the immune system and subsequent development of the glial scar. It should be reiterated that following injury in the vicinity of blood-brain barrier extravasation, much of the glial scar forms without astrocyte proliferation, but rather with a switch to the reactive state followed by inhibitory extracellular matrix (ECM) production and then hypertrophy. The growth inhibitory and growth promoting molecules exist in a balance that favors stalled regeneration of axons, but it is important to reiterate that non-regenerating axons still need to be supported if they are to remain indefinitely in the vicinity of the lesion.

This chapter focuses on the translation of extracellular cues to intracellular programs that are determinants of regenerative capacity. While the extracellular environment in the adult central nervous system (CNS) contains molecules that act as growth inhibitors, both in vitro and in vivo, co-culture experiments suggest that much of the failure of axon regeneration seen in the adult CNS can be attributed to a developmental reduction in the intrinsic regenerative ability of neurons. An irreversible loss of regenerative ability occurs at birth in rat retinal ganglion cell (RGC). Another indication of the importance of neuronintrinsic factors in determining the regenerative ability of axons is the heterogeneity in regenerative ability expressed by axons of different neurons growing through the same environment. The intrinsic growth capacity of an injured neuron is influenced by its external environment. Finally, the chapter presents some of the important extrinsic signals, and considers the intrinsic drivers of regeneration.