FIGURE 7.

Proposed model of astrocyte phenotype conversion. We propose a model in which a pro-inflammatory stimulus such as LPS activates NF-κB in astrocytes and promotes pathological remodeling of reactive astrocytes with pro-inflammatory gain of function only when microglia is present. In our in vitro paradigm, cell-to-cell communication to activate NF-κB nuclear translocation does not depend on physical contact with microglia but on the release of soluble factors. We propose that after NF-κB initial activation, the astrocyte reactive phenotype is sustained by epigenetic changes at the chromatin level.