Isolation and Characterization of Ischemia-Derived Astrocytes (IDAs) with Ability to Transactivate Quiescent Astrocytes

VILLAREAL ALEJANDRO; ROSCISZEWSKI GERARDO; MURTA VERÓNICA; CADENA VANESA; USACH VANINA; DODES TRAIAN MARTIN M.; SETTON, CLARA P; BARBEITO LUIS H; RAMOS ALBERTO J

Frontiers in cell neuroscience

Frontiers

Lugar: Laussanne; Año: 2016

Reactive gliosis involving activation and proliferation of astrocytes and microglia, is awidespread but largely complex and graded glial response to brain injury. Astroglialpopulation has a previously underestimated high heterogeneity with cells differing intheir morphology, gene expression profile, and response to injury. Here, we identifieda subset of reactive astrocytes isolated from brain focal ischemic lesions that showseveral atypical characteristics. Ischemia-derived astrocytes (IDAs) were isolated fromearly ischemic penumbra and core. IDA did not originate from myeloid precursors, butrather from pre-existing local progenitors. Isolated IDA markedly differ from primaryastrocytes, as they proliferate in vitro with high cell division rate, show increasedmigratory ability, have reduced replicative senescence and grow in the presence ofmacrophages within the limits imposed by the glial scar. Remarkably, IDA produce aconditioned medium that strongly induced activation on quiescent primary astrocytesand potentiated the neuronal death triggered by oxygen-glucose deprivation. Whenre-implanted into normal rat brains, eGFP-IDA migrated around the injection site andinduced focal reactive gliosis. Inhibition of gamma secretases or culture on quiescentprimary astrocytes monolayers facilitated IDA differentiation to astrocytes. We proposethat IDA represent an undifferentiated, pro-inflammatory, highly replicative and migratoryastroglial subtype emerging from the ischemic microenvironment that may contribute tothe expansion of reactive gliosis