Reactive astrocyte scar and axon regeneration: suppressor or facilitator?

Abstract

Several major factors are known to contribute to CNS axon regenerative failure after injury, including reduced intrinsic growth capacity of developed neurons and extrinsic factors mediating axon outgrowth. For the latter, a non-permissive environment around the lesion and the lack of sufficient neurotrophic support within the adult CNS play important roles (Silver et al., 2015). In addition to generation of various inhibitory substrates by oligodendrocytes, fibrotic tissues, inflammatory cells and other cell types, reactive astrocytes surrounding lesions are thought to highly suppress regeneration of injured CNS axons (Silver and Miller, 2004; Ohtake and Li, 2014). A great number of studies suggest that reactive astrocytic scars form one of the major barriers preventing axon regeneration after CNS injuries, including spinal cord injury (SCI). However, reactive astrocytes were reported to provide a beneficial role by reducing infiltrating immunoreactive cells into adjacent domains, protecting bordering neural tissue from damage and generating numerous supportive extracellular matrix (ECM) components to promote cell survival and growth (Bush et al., 1999). Previous data showed that ablation of reactive astrocytes increased inflammation and secondary tissue damage, prevented blood-brain barrier formation and increased local neurite growth. Interestingly, a recent study by Anderson et al (2016) provides evidence that reactive astrocytes around the lesioned spinal cord support axon regeneration after SCI, rather than block regrowth (Anderson et al., 2016).