Following injury to the adult central nervous system (CNS), injured axons are unable to regenerate past the lesion. Within the site of injury, referred to as the glial scar, reactive astrocytes produce chondroitin and keratan sulfate proteoglycans (CSPG/KSPG). These molecules are among the major inhibitory extracellular matrix (ECM) molecules believed to play a role in regeneration failure. The environment of the glial scar will be discussed in this chapter, with particular focus placed on the role of CSPGs in regeneration failure. The balance between CSPGs and growth promoting molecules produced by reactive astrocytes in the glial scar will be considered, as well as the behavior of regenerating neurons in the environment of CNS injury.

Introduction

The glial scar

With the exception of a small pathway in the hypothalamus (Chauvet et al., 1998) and the olfactory sensory projections within the olfactory bulb (Monti Graziadei et al., 1980; Morrison and Costanzo, 1995), severed axons within long myelinated tracks of the central nervous system (CNS) are capable only of abortive sprouting that provides little functional recovery (Ramón y Cajal, 1928; Li and Raisman, 1995). One of the major barriers to regeneration is the glial scar, in addition to myelin inhibitors (see Volume I, Chapter 21).