After focal ischemia, in addition to angiogenesis at the site of damage, adult VZ-SVZ-derived progenitors are proposed to proliferate and migrate to the site of injury (Arvidsson et al., 2002, Gotts and Chesselet, 2005a, Gotts and Chesselet, 2005b, Yamashita et al.,

2006 and Kojima et al., 2010). The close contact between adult VZ-SVZ progenitors and endothelial cells is again reminiscent of the embryonic and neonatal brain, in which neuroepithelial and radial glial progenitors also maintain basal contacts with the vasculature (Noctor et al., 2001). This contact also underscores the glial nature of adult neural stem cells, as astrocytes often maintain close contacts with blood vessels in the adult brain (Tavazoie et al., 2008). The close contact between type B1 cells and blood vessels suggests that vasculature-derived selleck inhibitor signals are important in regulation of neural stem cells, offering the promising prospect that identification of these signals could allow therapeutic reprogramming of other nongerminal areas and subsequent neuronal repopulation in the injured brain. In addition to being the birthplace of thousands of young neurons that likely have tonic secretion of neurotransmitters, the adult VZ-SVZ could also receive input via projections from neurons in adjoining or distant regions. A limited number of studies have focused on neurotransmitters and neural input in the regulation of adult

VZ-SVZ neurogenesis and have found roles for localized signaling via neurotransmitter production (reviewed in Young et al., 2011). The inhibitory neurotransmitter γ-aminobutyric acid (GABA) is produced by migrating type A cells. Type B cells express GABAA receptor

selleckchem and GABA transporters (Wang et al., 2003, Bolteus and Bordey, 2004 and Liu et al., 2005). GABA signaling appears to have two roles: it inhibits the proliferation of type B1 cells and slows the migration of type A neuroblasts. The production of GABA by immature neuroblasts has been proposed to act as a negative feedback mechanism to control proliferation of primary progenitors, which are closely associated with chains of migrating neuroblasts and are therefore through optimally positioned to respond to changes in local GABA concentration (Liu et al., 2005). In addition to GABA, the excitatory neurotransmitter glutamate has also been suggested to positively regulate neurogenesis, potentially by increasing transit-amplifying (type C) cells. Immunostaining within the adult VZ-SVZ has suggested that type B cells are a source of glutamate within this region (Platel et al., 2010). The precise populations of cells that are responsive to glutamate have not been identified, but cells within the RMS and olfactory bulb express functional AMPA/kainaite, NMDA, and glutamate receptors, implying that neuroblasts may also respond to glutamate and upregulate these receptors as they move toward the OB (Carleton et al., 2003, Platel et al., 2007, Platel et al., 2008b and Platel et al., 2010).