10.6084/m9.figshare.4785670.v1
Dawes W.J.
Dawes
W.J.
Zhang X.
Zhang
X.
Fancy S.P.J.
Fancy
S.P.J.
Rowitch D.
Rowitch
D.
Marino S.
Marino
S.
Supplementary Material for: Moderate-Grade Germinal Matrix Haemorrhage Activates Cell Division in the Neonatal Mouse Subventricular Zone
Karger Publishers
2017
Neural stem/progenitor cells
Postnatal gliogenesis
Postnatal neurogenesis
Germinal matrix haemorrhage
Mouse models
2017-03-24 11:48:37
Dataset
https://karger.figshare.com/articles/dataset/Supplementary_Material_for_Moderate-Grade_Germinal_Matrix_Haemorrhage_Activates_Cell_Division_in_the_Neonatal_Mouse_Subventricular_Zone/4785670
<p>Precise temporal and spatial control of the neural stem/progenitor
cells within the subventricular zone (SVZ) germinal matrix of the brain
is important for normal development in the third trimester and the early
postnatal period. The high metabolic demands of proliferating germinal
matrix precursors, coupled with the flimsy structure of the germinal
matrix cerebral vasculature, are thought to account for the high rates
of haemorrhage in extremely- and very-low-birth-weight preterm infants.
Germinal matrix haemorrhage can commonly extend to intraventricular
haemorrhage (IVH). Because neural stem/progenitor cells are sensitive to
microenvironmental cues from the ventricular, intermediate, and basal
domains within the germinal matrix, haemorrhage has been postulated to
impact neurological outcomes through aberration of normal neural
stem/progenitor cell behaviour. We developed an animal model of neonatal
germinal matrix haemorrhage using stereotactic injection of autologous
blood into the mouse neonatal germinal matrix. Pathological analysis at 4
days postinjury showed high rates of intraventricular extension and
ventricular dilatation but low rates of parenchymal disruption outside
the germinal zone, recapitulating key features of human “Papile grade
III” IVH. At 4 days postinjury we observed proliferation in the wall of
the lateral ventricle with significantly increased numbers of transient
amplifying cells within the SVZ and the corpus callosum. Analysis at 21
days postinjury revealed that cortical development was also affected,
with increased neuronal and concomitant reduced oligodendroglial
differentiation. At the molecular level, we showed downregulation of the
expression of the transmembrane receptor Notch2 in CD133<sup>+ve</sup>
cells of the SVZ, raising the possibility that the burst of precocious
proliferation seen in our experimental mouse model and the skewed
differentiation could be mediated by downregulation of the Notch pathway
within the proximal/ventricular domain. These findings raise the
possibility that Notch regulation plays a critical role in mediating the
response of the neonatal SVZ to ischaemic and haemorrhagic insults.</p>