Astrocyte precursor response to embryonic brain injury

Abstract

Penetrating traumatic insult during pregnancy is a leading cause of human fetal demise; in particular trauma to the brain may lead to devastating long-term cognitive sequelae. Perinatal brain injury involves glial precursors, but the neural mechanisms controlling astrocyte ontogeny after injury remain incompletely understood, partly due to a lack of appropriate markers and animal models. We analyzed astrocyte precursor response to injury at the beginning (E11) and peak (E15) of gliogenesis in an avian tectal model of penetrating embryonic brain trauma, without confounding maternal and sibling effects. At both ages, lateral ventricular dilatation, necrotic foci, periventricular cysts and intraventricular hemorrhages were observed distal to stab wounds two days after a unilateral stab injury to optic tecta. Neuronal (TUBB3) and oligodendrocyte precursor (PLP) markers were down-regulated, even far-removed from the wound site. In contrast, the mature astrocyte marker, GFAP, was up-regulated at the wound site, around necrotic areas and cysts, plus in usual areas of GFAP expression. Increased inflammatory response and apoptotic cell death were also confirmed in the injured tecta. Increased expression of NFIA, SOX9 and GLAST at the wound site and in the ventricular zone (VZ) of the injured tecta indicated an astroglial precursor response. However, cell division increased in the VZ only in early (E11) injury, but not later (E15), indicating that in late injury the astrogliogenesis occurring after acute injury is predominantly due to precursor differentiation rather than precursor proliferation. The inability to replenish the glial precursor pool during the critical period of vulnerability to injury may be an important cause of subsequent developmental abnormalities.

Delivery and Tracking of Quantum Dot Peptide Bioconjugates in an Intact Developing Avian Brain

“…We have previously used similar in situ hybridization assays to demonstrate increases in expression of astrocyte differentiation genes GFAP (glial fibrillary acidic protein), GLAST, and GS (glutamine synthase) in the nanomelic chick which lacks aggrecan (a proteoglycan with a major role in glial cell maturation) and in chick injury models. 18,35 Thus, the absence of any change in this expression is good evidence of lack of toxicity of the QDs and the chicks appeared normal at hatching.…”

“…18,35 cDNA fragments for SOX2 (SRY-related HMG-box gene 2) (nucleotides 402–948 of GenBank: D50603.1) was obtained by PCR from E8 chick brain cDNA using specific primers based on GenBank sequences. Riboprobes incorporating DIG-labeled nucleotides were synthesized from linearized plasmid templates with SP6 or T7 polymerase (Roche).…”

Characterization of nestin expression and vessel association in the ischemic core following focal cerebral ischemia in rats

“…Most (but not all) of the nestinpositive cells in the ischemic core were positive for Ki67 and exhibited nuclear Sox9 staining, indicating that the nestin-positive cells were highly proliferative and expressed a transcription factor found in neural and glial progenitor cells (Chu et al 2006;Domowicz et al 2011;Stolt et al 2003). In addition, nestin-positive cells had euchromatic nuclei with a prominent nucleolus.…”

“…3e-h). We then characterized these nestin-positive cells by double-labeling of nestin and the transcription factor Sox9, a marker for neural/glial progenitors (Chu et al 2006;Domowicz et al 2011;Stolt et al 2003). A majority of nestin-positive cells in the ischemic core exhibited nuclear Sox9 staining, although nestin-positive Sox9-negative cells were also found ( Fig.…”

Inhibition of glycogen synthase kinase-3 (GSK3) promotes the neural differentiation of full-term amniotic fluid-derived stem cells towards neural progenitor cells

“…Moreover, these cells acquired immunoreactivity for the neuron-specific marker class III ␤-tubulin (Tuj1), which indicated the post-mitotic neurons. Additionally, they also acquired immunoreactivity for GFAP, which is expressed in glia cells of the CNS, such as astrocytes and ependymal cells (Domowicz et al, 2012;Sheridan et al, 2012). Interestingly, the differentiated hAFS cells acquired immunoreactivity for the neural precursor cell markers NESTIN, post-mitotic neuron marker class III ␤-tubulin and glial marker GFAP at the same time.…”