An In Vitro Model of Reactive Astrogliosis and Its Effect on Neuronal Growth

Astrogliosis, whereby astrocytes in the central nervous system (CNS) become reactive in response to tissue damage, is a prominent process leading to the formation of the glial scar that inhibits axon regeneration after CNS injury. Upon becoming reactive, astrocytes undergo various molecular and morphological changes including upregulating their expression of GFAP and chondroitin sulfate proteoglycans (CSPGs) as well as other molecules that are inhibitory to axon growth. We have developed an in vitro model of reactive astrogliosis as a result of treating cultured astrocytes with transforming growth factor-β (TGF-β), which induces increased expression as well as secretion of CSPGs. These reactive astrocytes show inhibitory effects on neuron growth both in neuron-astrocyte coculture and in neurite guidance spot assay using astrocyte-conditioned medium. These reactive astrocytes provide a vehicle for testing substances that might overcome the glial scar and promote regeneration.