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2016 ; 10
(ä): 139
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Isolation and Characterization of Ischemia-Derived Astrocytes (IDAs) with Ability
to Transactivate Quiescent Astrocytes
#MMPMID27313509
Villarreal A
; Rosciszewski G
; Murta V
; Cadena V
; Usach V
; Dodes-Traian MM
; Setton-Avruj P
; Barbeito LH
; Ramos AJ
Front Cell Neurosci
2016[]; 10
(ä): 139
PMID27313509
show ga
Reactive gliosis involving activation and proliferation of astrocytes and
microglia, is a widespread but largely complex and graded glial response to brain
injury. Astroglial population has a previously underestimated high heterogeneity
with cells differing in their morphology, gene expression profile, and response
to injury. Here, we identified a subset of reactive astrocytes isolated from
brain focal ischemic lesions that show several atypical characteristics.
Ischemia-derived astrocytes (IDAs) were isolated from early ischemic penumbra and
core. IDA did not originate from myeloid precursors, but rather from pre-existing
local progenitors. Isolated IDA markedly differ from primary astrocytes, as they
proliferate in vitro with high cell division rate, show increased migratory
ability, have reduced replicative senescence and grow in the presence of
macrophages within the limits imposed by the glial scar. Remarkably, IDA produce
a conditioned medium that strongly induced activation on quiescent primary
astrocytes and potentiated the neuronal death triggered by oxygen-glucose
deprivation. When re-implanted into normal rat brains, eGFP-IDA migrated around
the injection site and induced focal reactive gliosis. Inhibition of gamma
secretases or culture on quiescent primary astrocytes monolayers facilitated IDA
differentiation to astrocytes. We propose that IDA represent an undifferentiated,
pro-inflammatory, highly replicative and migratory astroglial subtype emerging
from the ischemic microenvironment that may contribute to the expansion of
reactive gliosis. MAIN POINTS: Ischemia-derived astrocytes (IDA) were isolated
from brain ischemic tissue IDA show reduced replicative senescence, increased
cell division and spontaneous migration IDA potentiate death of oxygen-glucose
deprived cortical neurons IDA propagate reactive gliosis on quiescent astrocytes
in vitro and in vivo Inhibition of gamma secretases facilitates IDA
differentiation to astrocytes.