http://www.sciencedirect.com/science/article/pii/S0969996114003623
- Under a Creative Commons license
Open Access
Highlights
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- Stem cell niches exist along the entire ventricular system in the adult rat brain.
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- Stroke induces widespread neurogenesis and gliogenesis in all adult brain niches.
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- Niches access systemic injury cues via a permeable BBB, made leakier by stroke.
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- All stem cell niches are induced following bFGF infusion into the CSF.
Abstract
Previous
studies have established the subventricular (SVZ) and subgranular (SGZ)
zones as sites of neurogenesis in the adult forebrain (Doetsch et al., 1999a;
Doetsch, 2003a). Work from our laboratory further indicated that
midline structures known as circumventricular organs (CVOs) also serve
as adult neural stem cell (NSC) niches (Bennett et al., 2009, 2010). In
the quiescent rat brain, NSC proliferation remains low in all of these
sites. Therefore, we recently examined whether ischemic stroke injury
(MCAO) or sustained intraventricular infusion of the mitogen bFGF could
trigger an up-regulation in NSC proliferation, inducing neurogenesis and
gliogenesis. Our data show that both stroke and bFGF induce a dramatic
and long-lasting (14 day) rise in the proliferation (BrdU +) of
nestin + Sox2 + GFAP + NSCs capable of differentiating into Olig2 +
glial progenitors, GFAP + nestin-astrocyte progenitors and Dcx + neurons
in the SVZ and CVOs. Moreover, because of the upsurge in NSC number, it
was possible to detect for the first time several novel stem cell
niches along the third (3V) and fourth (4V) ventricles. Importantly, a
common feature of all brain niches was a rich vasculature with a
blood–brain-barrier (BBB) that was highly permeable to systemically
injected sodium fluorescein. These data indicate that stem cell niches
are more extensive than once believed and exist at multiple sites along
the entire ventricular system, consistent with the potential for
widespread neurogenesis and gliogenesis in the adult brain, particularly
after injury. We further suggest that because of their leaky BBB, stem
cell niches are well-positioned to respond to systemic injury-related
cues which may be important for stem-cell mediated brain repair.
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