Dissecting reactive astrogliosis: The conversion of astrocytes towards a reactive phenotype

VILLARREAL A, ANGELO MF, DODES TRAIAN M, BARBEITO L, RAMOS AJ

Huerta Grande, Córdoba, Argentina

Congreso; Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias (SAN); 2013

Reactive astrogliosis (RA) is a generic response to brain injury mediated by reactive astrocytes. During activation, it is proposed that astrocytes suffer a de-differentiation process. Evidence shows that RA contributes to neuronal protection as well as with expansion of focalized brain lesions. However these antagonizing roles of RA and the underlying mechanisms are still on debate. Here we show in vivo that reactive astrocytes (hypertrophied GFAP+ cells) overexpressed nestin in a time dependent manner after the onset of experimental brain ischemia. We were able to purify these cells in vitro by applying a protocol for establishment of primary cultures. Only ischemic tissue (but not control) was capable of rising proliferative cultures. Immunofluorescence studies for nestin, vimentin, GFAP and BrdU incorporation revealed an undifferentiated astrocytic phenotype and a high proliferation rate compared to primary astrocytes. Even more, conditioned medium obtained from these cells induced the RA and proliferation of naïve astrocytes, proliferation, but also neuronal protection to OGD. Our results indicate that the proinflammatory environment generated after ischemic stroke induces activation of astrocytes towards a reactive and undifferentiated phenotype. These reactive astrocytes proliferate in vitro and have the potentiality of activating naïve astrocytes probably by secretion of proinflammatory cytokines thus contributing to sustain RA.