Effects of the glial scar and extracellular matrix molecules on axon regeneration

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.