Cell and Tissue Research

, Volume 371, Issue 1, pp 125–141 | Cite as

Home sweet home: the neural stem cell niche throughout development and after injury

  • Rebecca M. Ruddy
  • Cindi M. MorsheadEmail author


Neural stem cells and their progeny reside in two distinct neurogenic niches within the mammalian brain: the subventricular zone and the dentate gyrus. The interplay between the neural stem cells and the niche in which they reside can have significant effects on cell kinetics and neurogenesis. A comprehensive understanding of the changes to the niche that occur through postnatal development and aging, as well as following injury, is relevant for developing therapeutics and interventions to promote neural repair. We discuss changes that occur within the neural stem and progenitor cell populations, the vasculature, extracellular matrix, microglia, and secreted proteins through aging which impact cell behavior within the neurogenic niches. We examine neural precursor cell and niche responses to injury in neonatal hypoxia-ischemia, juvenile cranial irradiation, and adult stroke. This review examines the interplay between the niche and stem cell behavior through aging and following injury as a means to understand intrinsic and extrinsic factors that regulate neurogenesis in vivo.


Neural stem cell Stroke Irradiation Aging Neonatal 


  1. Ables JL, DeCarolis NA, Johnson MA, Rivera PD, Gao Z, Cooper DC et al (2010) Notch1 is required for maintenance of the reservoir of adult hippocampal stem cells. J Neurosci 30(31):10484–10492. doi: 10.1038/nature09421.Oxidative PubMedPubMedCentralCrossRefGoogle Scholar
  2. Alonso M, Viollet C, Gabellec MM, Meas-Yedid V, Olivo-Marin JC, Lledo PM (2006) Olfactory discrimination learning increases the survival of adult-born neurons in the olfactory bulb. J Neurosci 26(41):10508–10513. doi: 10.1523/JNEUROSCI.2633-06.2006 PubMedCrossRefGoogle Scholar
  3. Altman J, Bayer SA (1990) Migration and distribution of two populations of hippocampal granule cell precursors during the perinatal and postnatal periods. J Comp Neurol 301(3):365–381. doi: 10.1002/cne.903010304 PubMedCrossRefGoogle Scholar
  4. Alvarez-Buylla A, García-Verdugo JM (2002) Neurogenesis in adult subventricular zone. J Neurosci 22(3):629–634PubMedGoogle Scholar
  5. Arvidsson A, Kokaia Z, Lindvall O (2001) N-methyl-D-aspartate receptor-mediated increase of neurogenesis in adult rat dentate gyrus following stroke. Eur J Neurosci 14(1):10–18. doi: 10.1046/j.0953-816x.2001.01611.x PubMedCrossRefGoogle Scholar
  6. Arvidsson A, Collin T, Kirik D, Kokaia Z, Lindvall O (2002) Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat Med 8(9):963–970. doi: 10.1038/nm747 PubMedCrossRefGoogle Scholar
  7. Barker JM, Galea LAM (2008) Repeated estradiol administration alters different aspects of neurogenesis and cell death in the hippocampus of female, but not male, rats. Neuroscience 152(4):888–902. doi:  10.1016/j.neuroscience.2007.10.071 PubMedCrossRefGoogle Scholar
  8. Barondes SH, Castronovo V, Cooper DNW, Cummings RD, Drickamer K, Felzi T et al (1994) Galectins: a family of animal ??-galactoside-binding lectins. Cell 76(4):597–598. doi: 10.1016/0092-8674(94)90498-7 PubMedCrossRefGoogle Scholar
  9. Bednarczyk MR, Hacker LC, Fortin-Nunez S, Aumont A, Bergeron R, Fernandes KJL (2011) Distinct stages of adult hippocampal neurogenesis are regulated by running and the running environment. Hippocampus 21(12):1334–1347. doi: 10.1002/hipo.20831 PubMedCrossRefGoogle Scholar
  10. Ben Abdallah NMB, Slomianka L, Vyssotski AL, Lipp HP (2010) Early age-related changes in adult hippocampal neurogenesis in C57 mice. Neurobiol Aging 31(1):151–161. doi: 10.1016/j.neurobiolaging.2008.03.002 PubMedCrossRefGoogle Scholar
  11. Boström M, Kalm M, Karlsson N, Hellström Erkenstam N, Blomgren K (2013) Irradiation to the young mouse brain caused long-term, progressive depletion of neurogenesis but did not disrupt the neurovascular niche. J Cereb Blood Flow Metab 33(6):935–943. doi: 10.1038/jcbfm.2013.34 PubMedPubMedCentralCrossRefGoogle Scholar
  12. Boström M, Hellström Erkenstam N, Kaluza D, Jakobsson L, Kalm M, Blomgren K (2014) The hippocampal neurovascular niche during normal development and after irradiation to the juvenile mouse brain. Int J Radiat Biol 3002(May):1–27. doi: 10.3109/09553002.2014.931612 Google Scholar
  13. Bouab M, Paliouras GN, Aumont A, Forest-Bérard K, Fernandes KJL (2011) Aging of the subventricular zone neural stem cell niche: evidence for quiescence-associated changes between early and mid-adulthood. Neuroscience 173:135–149. doi: 10.1016/j.neuroscience.2010.11.032 PubMedCrossRefGoogle Scholar
  14. Braccioli L, Heijnen CJ, Coffer PJ, Nijboer CH (2016) Delayed administration of neural stem cells after hypoxia-ischemia reduces sensorimotor deficits, cerebral lesion size and neuroinflammation in neonatal mice. Pediatr Res 81(February):127–135. doi: 10.1038/pr.2016.172 PubMedGoogle Scholar
  15. Breunig JJ, Silbereis J, Vaccarino FM, Sestan N, Rakic P (2007) Notch regulates cell fate and dendrite morphology of newborn neurons in the postnatal dentate gyrus. Proc Natl Acad Sci U S A 104(51):20558–20563. doi: 10.1073/pnas.0710156104 PubMedPubMedCentralCrossRefGoogle Scholar
  16. Brooker SM, Bond AM, Peng CY, Kessler JA (2016) ??1-integrin restricts astrocytic differentiation of adult hippocampal neural stem cells. Glia 64(7):1235–1251. doi: 10.1002/glia.22996 PubMedCrossRefGoogle Scholar
  17. Capilla-Gonzalez V, Cebrian-Silla A, Guerrero-Cazares H, Garcia-Verdugo JM, Quiñones-Hinojosa A (2014) Age-related changes in astrocytic and ependymal cells of the subventricular zone. Glia 62(5):790–803. doi: 10.1002/glia.22642 PubMedPubMedCentralCrossRefGoogle Scholar
  18. Chaker Z, Aı S, Berry H, Holzenberger M (2015) Suppression of IGF-I signals in neural stem cells enhances neurogenesis and olfactory function during aging. Aging Cell 14(May):847–856. doi: 10.1111/acel.12365 PubMedPubMedCentralCrossRefGoogle Scholar
  19. Chodobski A, Szmydynger-Chodobska J (2001) Choroid plexus: target for polypeptides and site of their synthesis. Microsc Res Tech 52(1):65–82. doi: 10.1002/1097-0029(20010101)52:1>65:AID-JEMT9>3.0.CO;2-4
  20. Clarke L, Van Der Kooy D (2011) The adult mouse dentate gyrus contains populations of committed progenitor cells that are distinct from subependymal zone neural stem cells. Stem Cells 29(9):1448–1458. doi: 10.1002/stem.692 PubMedGoogle Scholar
  21. Codega P, Silva-Vargas V, Paul A, Maldonado-Soto AR, DeLeo AM, Pastrana E, Doetsch F (2014) Prospective identification and purification of quiescent adult neural stem cells from their in vivo niche. Neuron 82(3):545–559. doi: 10.1016/j.neuron.2014.02.039 PubMedPubMedCentralCrossRefGoogle Scholar
  22. Comte I, Kim Y, Young CC, van der Harg JM, Hockberger P, Bolam PJ et al (2011) Galectin-3 maintains cell motility from the subventricular zone to the olfactory bulb. J Cell Sci 124(Pt 14):2438–2447. doi: 10.1242/jcs.079954 PubMedPubMedCentralCrossRefGoogle Scholar
  23. Conover JC, Shook BA (2011) Aging of the Subventricular zone neural stem cell Niche : evidence for quiescence-associated changes between early and mid-adulthood. Aging Dis 2(1):49–63. doi: 10.1016/j.neuroscience.2010.11.032 PubMedPubMedCentralGoogle Scholar
  24. Covey MV, Levison SW (2007) Leukemia inhibitory factor participates in the expansion of neural stem/progenitors after perinatal hypoxia/ischemia. Neuroscience 148(2):501–509. doi: 10.1016/j.immuni.2010.12.017.Two-stage PubMedPubMedCentralCrossRefGoogle Scholar
  25. Craig CG, Tropepe V, Morshead CM, Reynolds BA, Weiss S, Van der Kooy D (1996) In vivo growth factorexpansion of endogenous subependymal neural precursor cell populations in the adult mousebrain. J Neurosci 16:2649–2658Google Scholar
  26. Craig CG, D’Sa R, Morshead CM, Roach A, Van Der Kooy D (1999) Migrational analysis of the constitutively proliferating subependyma population in adult mouse forebrain. Neuroscience 93(3):1197–1206. doi: 10.1016/S0306-4522(99)00232-8 PubMedCrossRefGoogle Scholar
  27. Dadwal P, Mahmud N, Sinai L, Azimi A, Fatt M, Wondisford FE et al (2015) Activating endogenous neural precursor cells using metformin leads to neural repair and functional recovery in a model of childhood brain injury. Stem Cell Rep 5(2):166–173. doi: 10.1016/j.stemcr.2015.06.011 CrossRefGoogle Scholar
  28. Dalmau I, Finsen B, Zimmer J, González B, Castellano B (1998) Development of microglia in the postnatal rat hippocampus. Hippocampus 8(5):458–474. doi: 10.1002/(SICI)1098-1063(1998)8:5<458::AID-HIPO6>3.0.CO;2-N PubMedCrossRefGoogle Scholar
  29. Deierborg T, Roybon L, Inacio AR, Pesic J, Brundin P (2010) Brain injury activates microglia that induce neural stem cell proliferation ex vivo and promote differentiation of neurosphere-derived cells into neurons and oligodendrocytes. Neuroscience 171(4):1386–1396. doi: 10.1016/j.neuroscience.2010.09.045 PubMedCrossRefGoogle Scholar
  30. Doetsch F (2003) A niche for adult neural stem cells. Curr Opin Genet Dev 13(5):543–550. doi: 10.1016/j.gde.2003.08.012 PubMedCrossRefGoogle Scholar
  31. Doetsch F, Petreanu L, Caille I, Garcia-Verdugo JM, Alvarez-Buylla A (2002) EGF converts transit-amplifying neurogenic precursors in the adult brain into multipotent stem cells. Neuron 36(6):1021–1034. doi: 10.1016/S0896-6273(02)01133-9 PubMedCrossRefGoogle Scholar
  32. Douet V, Kerever A, Arikawa-Hirasawa E, Mercier F (2013) Fractone-heparan sulphates mediate FGF-2 stimulation of cell proliferation in the adult subventricular zone. Cell Prolif 46(2):137–145. doi: 10.1111/cpr.12023 PubMedCrossRefGoogle Scholar
  33. Encinas JM, Michurina TV, Peunova N, Park JH, Tordo J, Peterson DA et al (2011) Division-coupled astrocytic differentiation and age-related depletion of neural stem cells in the adult hippocampus. Cell Stem Cell 8(5):566–579. doi: 10.1016/j.stem.2011.03.010 PubMedPubMedCentralCrossRefGoogle Scholar
  34. Enwere E (2004) Aging results in reduced epidermal growth factor receptor signaling, diminished olfactory neurogenesis, and deficits in fine olfactory discrimination. J Neurosci 24(38):8354–8365. doi: 10.1523/JNEUROSCI.2751-04.2004 PubMedCrossRefGoogle Scholar
  35. Farmer J, Zhao X, Van Praag H, Wodtke K, Gage FH, Christie BR (2004) Effects of voluntary exercise on synaptic plasticity and gene expression in the dentate gyrus of adult male sprague-dawley rats in vivo. Neuroscience 124(1):71–79. doi: 10.1016/j.neuroscience.2003.09.029 PubMedCrossRefGoogle Scholar
  36. Felling RJ, Covey MV, Wolujewicz P, Batish M, Levison SW (2016) Astrocyte-produced leukemia inhibitory factor expands the neural stem/progenitor pool following perinatal hypoxia-ischemia. J Neurosci Res 94(12):1531–1545. doi: 10.1002/jnr.23929 PubMedPubMedCentralCrossRefGoogle Scholar
  37. Fiorelli R, Azim K, Fischer B, Raineteau O (2015) Adding a spatial dimension to postnatal ventricular-subventricular zone neurogenesis. Development 142(12):2109–2120. doi: 10.1242/dev.119966 PubMedCrossRefGoogle Scholar
  38. Frotscher M (2010) Role for Reelin in stabilizing cortical architecture. Trends Neurosci 33(9):407–414. doi: 10.1016/j.tins.2010.06.001 PubMedCrossRefGoogle Scholar
  39. Fukuda A, Fukuda H, Swanpalmer J, Hertzman S, Lannering B, Marky I et al (2005) Age-dependent sensitivity of the developing brain to irradiation is correlated with the number and vulnerability of progenitor cells. J Neurochem 92(3):569–584. doi: 10.1111/j.1471-4159.2004.02894.x PubMedCrossRefGoogle Scholar
  40. Furuta M, Bridges RS (2005) Gestation-induced cell proliferation in the rat brain. Dev Brain Res 156(1):61–66. doi: 10.1016/j.devbrainres.2005.01.008 CrossRefGoogle Scholar
  41. Gilley JA, Yang C-P, Kernie SG (2011) Developmental profiling of postnatal dentate gyrus progenitors provides evidence for dynamic cell-autonomous regulation. Hippocampus 21(1):33–47. doi: 10.1016/j.immuni.2010.12.017.Two-stage PubMedPubMedCentralCrossRefGoogle Scholar
  42. Hack I, Bancila M, Loulier K, Carroll P, Cremer H (2002) Reelin is a detachment signal in tangential chain-migration during postnatal neurogenesis. Nat Neurosci 5(10):939–945. doi: 10.1038/nn923 PubMedCrossRefGoogle Scholar
  43. Hagberg H, Mallard C, Ferriero DM, Vannucci SJ, Levison SW, Vexler ZS, Gressens P (2015) The role of inflammation in perinatal brain injury. Nat Rev Neurol 11(4):192–208. doi: 10.1038/nbt.3121.ChIP-nexus PubMedPubMedCentralCrossRefGoogle Scholar
  44. Hamilton LK, Joppé SE, M Cochard L, Fernandes KJL (2013) Aging and neurogenesis in the adult forebrain: what we have learned and where we should go from here. Eur J Neurosci 37(12):1978–1986. doi: 10.1111/ejn.12207 PubMedCrossRefGoogle Scholar
  45. Hedtjarn M, Mallard C, Hagberg H (2004) Inflammatory gene profiling in the developing mouse brain after hypoxia-ischemia. J Cereb Blood Flow Metab 24(12):1333–1351. doi: 10.1097/01.wcb.0000141559.17620.36 PubMedCrossRefGoogle Scholar
  46. Hirota Y, Sawada M, Huang SH, Ogino T, Ohata S, Kubo A, Sawamoto K (2016) Roles of wnt signaling in the neurogenic niche of the adult mouse ventricular-subventricular zone. Neurochem Res 41(1–2):222–230. doi: 10.1007/s11064-015-1766-z PubMedCrossRefGoogle Scholar
  47. Hitoshi S, Alexson T, Tropepe V, Donoviel D, Elia AJ, Nye JS et al (2002) Notch pathway molecules are essential for the maintenance, but not the generation, of mammalian neural stem cells. Genes Dev 16(7):846–858. doi: 10.1101/gad.975202 PubMedPubMedCentralCrossRefGoogle Scholar
  48. Huo K, Sun Y, Li H, Du X, Wang X, Karlsson N (2012) Lithium reduced neural progenitor apoptosis in the hippocampus and ameliorated functional de fi cits after irradiation to the immature mouse brain. Mol Cell Neurosci 51(1–2):32–42. doi: 10.1016/j.mcn.2012.07.002 PubMedCrossRefGoogle Scholar
  49. Hurtado-Chong A, Yusta-Boyo MJ, Vergaño-Vera E, Bulfone A, De Pablo F, Vicario-Abejón C (2009) IGF-I promotes neuronal migration and positioning in the olfactory bulb and the exit of neuroblasts from the subventricular zone. Eur J Neurosci 30(5):742–755. doi: 10.1111/j.1460-9568.2009.06870.x PubMedCrossRefGoogle Scholar
  50. Ieraci A, Madaio AI, Mallei A, Lee FS, Popoli M (2016) Brain derived neurotrophic factor Val66Met human polymorphism impairs the beneficial exercise-induced neurobiological changes in mice. Neuropsychopharmacology 41(May):1–35. doi: 10.1038/npp.2016.120 Google Scholar
  51. Imayoshi I, Sakamoto M, Yamaguchi M, Mori K, Kageyama R (2010) Essential roles of Notch signaling in maintenance of neural stem cells in developing and adult brains. J Neurosci 30(9):3489–3498. doi: 10.1523/JNEUROSCI.4987-09.2010 PubMedCrossRefGoogle Scholar
  52. Jenrow KA, Brown SL, Lapanowski K, Naei H, Kolozsvary A, Kim JH (2013) Selective inhibition of microglia-mediated neuroinflammation mitigates radiation-induced cognitive impairment. Radiat Res 179(5):549–556. doi: 10.1667/RR3026.1 PubMedPubMedCentralCrossRefGoogle Scholar
  53. Jin K, Minami M, Lan JQ, Mao XO, Batteur S, Simon RP, Greenberg DA (2001) Neurogenesis in dentate subgranular zone and rostral subventricular zone after focal cerebral ischemia in the rat. Proc Natl Acad Sci U S A 98(8):4710–4715. doi: 10.1073/pnas.081011098 PubMedPubMedCentralCrossRefGoogle Scholar
  54. Jin K, Sun Y, Xie L, Batteur S, Mao XO, Smelick C et al (2003) Neurogenesis and aging: FGF-2 and HB-EGF restore neurogenesis in hippocampus and subventricular zone of aged mice. Aging Cell 2(3):175–183. doi: 10.1046/j.1474-9728.2003.00046.x PubMedCrossRefGoogle Scholar
  55. Jung Y, Brack AS (2014) Cellular mechanisms of somatic stem cell aging. Curr Top Dev Biol:107:405–438. doi:  10.1016/B978-0-12-416022-4.00014-7
  56. Kang W, Hebert JM (2015) FGF signaling is necessary for neurogenesis in young mice and sufficient to reverse its decline in old mice. J Neurosci 35(28):10217–10223. doi: 10.1523/JNEUROSCI.1469-15.2015 PubMedPubMedCentralCrossRefGoogle Scholar
  57. Katsimpardi L, Litterman NK, Schein PA, Miller CM, Loffredo FS, Wojtkiewicz GR et al (2014) Vascular and neurogenic rejuvenation of the aging mouse brain by young systemic factors. Science 344:630–634PubMedPubMedCentralCrossRefGoogle Scholar
  58. Kerever A, Schnack J, Vellinga D, Ichikawa N, Moon C, Arikawa-Hirasawa E et al (2007) Novel extracellular matrix structures in the neural stem cell niche capture the neurogenic factor fibroblast growth factor 2 from the extracellular milieu. Stem Cells 25(9):2146–2157. doi: 10.1634/stemcells.2007-0082 PubMedCrossRefGoogle Scholar
  59. Klempin F, Beis D, Mosienko V, Kempermann G, Bader M, Alenina N (2013) Serotonin is required for exercise-induced adult hippocampal neurogenesis. J Neurosci 33(19):8270–8275. doi: 10.1523/JNEUROSCI.5855-12.2013 PubMedCrossRefGoogle Scholar
  60. Kuhn HG, Dickinson-Anson H, Gage FH (1996) Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci 16(6):2027–2033PubMedGoogle Scholar
  61. Kuhn HG, Winkler J, Kempermann G, Thal LJ, Gage FH (1997) Epidermal growth factor and fibroblast growth factor-2 have different effects on neural progenitors in the adult rat brain. J Neurosci 17(15):5820–5829PubMedGoogle Scholar
  62. Lalli G (2014) Neuroblast migration in the postnatal brain. Adv Exp Med Biol 800:149–180. doi: 10.1007/978-94-007-7687-6
  63. Lavado A, Oliver G (2014) Jagged1 is necessary for postnatal and adult neurogenesis in the dentate gyrus. Dev Biol 388(1):11–21. doi: 10.1016/j.ydbio.2014.02.004 PubMedPubMedCentralCrossRefGoogle Scholar
  64. Lecanu L (2011) Sex, the underestimated potential determining factor in brain tissue repair strategy. Stem Cells Dev 20(12):2031–2035. doi: 10.1089/scd.2011.0188 PubMedCrossRefGoogle Scholar
  65. Levison SW, Rothstein RP, Romanko MJ, Synder MJ, Meyers RL, Vannucci SJ (2001) Hypoxia / ischemia depletes the rat perinatal Subventricular zone of oligodendrocytes progenitors and neural stem cells. Dev Neurosci 23:234–247PubMedCrossRefGoogle Scholar
  66. Li G, Pleasure SJ (2005) Morphogenesis of the dentate gyrus: what we are learning from mouse mutants. Dev Neurosci 27(2–4):93–99. doi: 10.1159/000085980 PubMedCrossRefGoogle Scholar
  67. Li Q, Li H, Roughton K, Wang X, Kroemer G, Blomgren K, Zhu C (2010) Lithium reduces apoptosis and autophagy after neonatal hypoxia-ischemia. Cell Death Dis 1:e56. doi: 10.1038/cddis.2010.33 PubMedPubMedCentralCrossRefGoogle Scholar
  68. Li H, Li Q, Du X, Sun Y, Wang X, Kroemer G et al (2011) Lithium-mediated long-term neuroprotection in neonatal rat hypoxia-ischemia is associated with antiinflammatory effects and enhanced proliferation and survival of neural stem/progenitor cells. J Cereb Blood Flow Metab 31(10):2106–2115. doi: 10.1038/jcbfm.2011.75 PubMedPubMedCentralCrossRefGoogle Scholar
  69. Lichtenwalner RJ, Forbes ME, Bennett SA, Lynch CD, Sonntag WE, Riddle DR (2001) Intracerebroventricular infusion of insulin-like growth factor-I ameliorates the age-related decline in hippocampal neurogenesis. Neuroscience 107(4):603–613. doi: 10.1016/S0306-4522(01)00378-5 PubMedCrossRefGoogle Scholar
  70. Lie DC, Colamarino SA, Song HJ, Désiré L, Mira H, Consiglio A et al (2005) Wnt signalling regulates adult hippocampal neurogenesis. Nature 437(7063):1370–1375. doi: 10.1038/nature04108 PubMedCrossRefGoogle Scholar
  71. Lim DA, Alvarez-buylla A (2016) The adult ventricular – subventricular zone. Cold Spring Harb Perspect Biol 8:1–34Google Scholar
  72. Lim DA, Tramontin AD, Trevejo JM, Herrera DG, García-Verdugo JM, Alvarez-Buylla A (2000) Noggin antagonizes BMP signaling to create a niche for adult neurogenesis. Neuron 28(3):713–726. doi: 10.1016/S0896-6273(00)00148-3 PubMedCrossRefGoogle Scholar
  73. Lin TN, Te J, Lee M, Sun GY, Hsu CY (1997) Induction of basic fibroblast growth factor (bFGF) expression following focal cerebral ischemia. Brain Research. Mol Brain Res 49(1–2):255–265PubMedCrossRefGoogle Scholar
  74. Liu M, Pleasure SJ, Collins AE, Noebels JL, Naya FJ, Tsai MJ, Lowenstein DH (2000) Loss of BETA2/NeuroD leads to malformation of the dentate gyrus and epilepsy. Proc Natl Acad Sci U S A 97(2):865–870. doi: 10.1073/pnas.97.2.865 PubMedPubMedCentralCrossRefGoogle Scholar
  75. Lugert S, Basak O, Knuckles P, Haussler U, Fabel K, Götz M et al (2010) Quiescent and active hippocampal neural stem cells with distinct morphologies respond selectively to physiological and pathological stimuli and aging. Cell Stem Cell 6(5):445–456. doi: 10.1016/j.stem.2010.03.017 PubMedCrossRefGoogle Scholar
  76. Mabbott DJ, Spiegler BJ, Greenberg ML, Rutka JT, Hyder DJ, Bouffet E (2005) Serial evaluation of academic and behavioral outcome after treatment with cranial radiation in childhood. J Clin Oncol 23(10):2256–2263. doi: 10.1200/JCO.2005.01.158 PubMedCrossRefGoogle Scholar
  77. Mabbott DJ, Noseworthy MD, Bouffet E, Rockel C, Laughlin S (2006) Diffusion tensor imaging of white matter after cranial radiation in children for medulloblastoma: correlation with IQ. Neuro-Oncology 8(3):244–252. doi: 10.1215/15228517-2006-002 PubMedPubMedCentralCrossRefGoogle Scholar
  78. Maekawa M, Takashima N, Arai Y, Nomura T, Inokuchi K, Yuasi S, Osumi N (2005) Pax6 is required for production and maintenance of progenitor cells in postnatal hippocampal neurogenesis. Genes Cells 10(10):1001–1014. doi: 10.1111/j.1365-2443.2005.00893.x PubMedCrossRefGoogle Scholar
  79. Mak GK, Enwere EK, Gregg C, Pakarainen T, Poutanen M, Huhtaniemi I, Weiss S (2007) Male pheromone-stimulated neurogenesis in the adult female brain: possible role in mating behavior. Nat Neurosci 10(8):1003–1011. doi: 10.1038/nn1928 PubMedCrossRefGoogle Scholar
  80. Malaterre J, McPherson CS, Denoyer D, Lai E, Hagekyriakou J, LAI E, … Ramsay RG (2012) Enhanced lithium-induced brain recovery following cranial irradiation is not impeded by inflammation. Stem Cells Transl Med 1:469–479Google Scholar
  81. Massalini S, Pellegatta S, Pisati F, Finocchiaro G, Farace MG, Ciafrè SA (2009) Reelin affects chain-migration and differentiation of neural precursor cells. Mol Cell Neurosci 42(4):341–349. doi: 10.1016/j.mcn.2009.08.006 PubMedCrossRefGoogle Scholar
  82. Mirzadeh Z, Merkle FT, Soriano-navarro M, Garcia-verdugo JM (2008) Neural stem cells confer unique pinwheel architecture to the ventricular surface in neurogenic regions of the adult brain. Cell Stem Cell 3:265–278. doi: 10.1016/j.stem.2008.07.004
  83. Monje ML, Mizumatsu S, Fike JR, Palmer TD (2002) Irradiation induces neural precursor-cell dysfunction. Nat Med 8(9):955–962. doi: 10.1038/nm749 PubMedCrossRefGoogle Scholar
  84. Monje ML, Vogel H, Masek M, Ligon KL, Fisher PG, Palmer TD (2007) Impaired human hippocampal neurogenesis after treatment for central nervous system malignancies. Ann Neurol 62(5):515–520. doi: 10.1002/ana.21214 PubMedCrossRefGoogle Scholar
  85. Moreno MM, Linster C, Escanilla O, Sacquet J, Didier A, Mandairon N (2009) Olfactory perceptual learning requires adult neurogenesis. Proc Natl Acad Sci U S A 106(42):17980–17985. doi: 10.1073/pnas.0907063106 PubMedPubMedCentralCrossRefGoogle Scholar
  86. Morshead CM, Reynolds BA, Craig CG, McBurney MW, Staines WA, Morassutti D et al (1994) Neural stem cells in the adult mammalian forebrain: a relatively quiescent subpopulation of subependymal cells. Neuron 13(5):1071–1082. doi: 10.1016/0896-6273(94)90046-9 PubMedCrossRefGoogle Scholar
  87. Morshead CM, Craig CG, van der Kooy D (1998) In vivo clonal analyses reveal the properties of endogenous neural stem cell proliferation in the adult mammalian forebrain. Development 125:2251–2261PubMedGoogle Scholar
  88. Motomura K, Ogura M, Natsume A, Yokoyama H (2010) Neuroscience letters a free-radical scavenger protects the neural progenitor cells in the dentate subgranular zone of the hippocampus from cell death after X-irradiation. Neurosci Lett 485(1):65–70. doi: 10.1016/j.neulet.2010.08.065 PubMedCrossRefGoogle Scholar
  89. Mudò G, Bonomo A, Di Liberto V, Frinchi M, Fuxe K, Belluardo N (2009) The FGF-2/FGFRs neurotrophic system promotes neurogenesis in the adult brain. J Neural Transm 116(8):995–1005. doi: 10.1007/s00702-009-0207-z PubMedCrossRefGoogle Scholar
  90. Naylor AS, Bull C, Nilsson MKL, Zhu C, Björk-Eriksson T, Eriksson PS et al (2008) Voluntary running rescues adult hippocampal neurogenesis after irradiation of the young mouse brain. Proc Natl Acad Sci U S A 105(38):14632–14637. doi: 10.1073/pnas.0711128105 PubMedPubMedCentralCrossRefGoogle Scholar
  91. Ness JK, Romanko MJ, Rothstein RP, Wood TL, Levison SW (2001) Perinatal hypoxia-ischemia induces apoptotic and excitotoxic death of periventricular white matter oligodendrocyte progenitors. Dev Neurosci 23(3):203–208. doi: 10.1159/000046144 PubMedCrossRefGoogle Scholar
  92. Nicola Z, Fabel K, Kempermann G (2015) Development of the adult neurogenic niche in the hippocampus of mice. Front Neuroanat 9(May):53. doi: 10.3389/fnana.2015.00053 PubMedPubMedCentralGoogle Scholar
  93. Nie K, Molnár Z, Szele FG (2010) Proliferation but not migration is associated with blood vessels during development of the rostral migratory stream. Dev Neurosci 32(3):163–172. doi: 10.1159/000301135 PubMedPubMedCentralCrossRefGoogle Scholar
  94. Nieto-Estevez V, Defterali C, Vicario-Abejon C (2016) IGF-I: a key growth factor that regulates neurogenesis and synaptogenesis from embryonic to adult stages of the brain. Front Neurosci 10(Feb):1–9. doi: 10.3389/fnins.2016.00052 Google Scholar
  95. Nogami H, Hoshino R, Ogasawara K, Miyamoto S, Hisano S (2007) Region-specific expression and hormonal regulation of the first exon variants of rat prolactin receptor mRNA in rat brain and anterior pituitary gland. J Neuroendocrinol 19(8):583–593. doi: 10.1111/j.1365-2826.2007.01565.x PubMedCrossRefGoogle Scholar
  96. O’Keeffe GC, Tyers P, Aarsland D, Dalley JW, Barker RA, Caldwell MA (2009) Dopamine-induced proliferation of adult neural precursor cells in the mammalian subventricular zone is mediated through EGF. Proc Natl Acad Sci U S A 106(21):8754–8759. doi: 10.1073/pnas.0803955106 PubMedPubMedCentralCrossRefGoogle Scholar
  97. Okamoto M, Inoue K, Iwamura H, Terashima K, Soya H, Asashima M, Kuwabara T (2011) Reduction in paracrine Wnt3 factors during aging causes impaired adult neurogenesis. FASEB J 25(10):3570–3582. doi: 10.1096/fj.11-184697 PubMedCrossRefGoogle Scholar
  98. Ong J, Plane JM, Parent JM, Silverstein FS (2005) Hypoxic-ischemic injury stimulates subventricular zone proliferation and neurogenesis in the neonatal rat. Pediatr Res 58(3):600–606. doi: 10.1203/01.PDR.0000179381.86809.02 PubMedCrossRefGoogle Scholar
  99. Ottone C, Parrinello S (2015) Multifaceted control of adult SVZ neurogenesis by the vascular niche. Cell Cycle 14(14):2222–2225. doi: 10.1080/15384101.2015.1049785 PubMedPubMedCentralCrossRefGoogle Scholar
  100. Packer BRJ, Goldwein J, Nicholson HS, Vezina LG, Allen JC, Ris MD et al (2017) Treatment of children with medulloblastoma with reduced-dose craniospinal radiation therapy and adjuvant chemotherapy: a Children’s Cancer Group study. J Clin Oncol 17(7):2127–2136Google Scholar
  101. Palmer TD, Willhoite AR, Gage FH (2000) Vascular niche for adult hippocampal neurogenesis. J Comp Neurol 425(4):479–494. doi: 10.1002/1096-9861(20001002)425:4<479::AID-CNE2>3.0.CO;2-3 PubMedCrossRefGoogle Scholar
  102. Palmer SL, Armstrong C, Onar-Thomas A, Wu S, Wallace D, Bonner MJ et al (2013) Processing speed, attention, and working memory after treatment for medulloblastoma: an international, prospective, and longitudinal study. J Clin Oncol 31(28):3494–3500. doi: 10.1200/JCO.2012.47.4775 PubMedPubMedCentralCrossRefGoogle Scholar
  103. Pastrana E, Cheng L-CC, Doetsch F (2009) Simultaneous prospective purification of adult subventricular zone neural stem cells and their progeny. Proc Natl Acad Sci U S A 106(15):6387–6392. doi: 10.1073/pnas.0810407106 PubMedPubMedCentralCrossRefGoogle Scholar
  104. Peretto P, Merighi A, Fasolo A, Bonfanti L (1999) The subependymal layer in rodents: a site of structural plasticity and cell migration in the adult mammalian brain. Brain Res Bull 49(4):221–243. doi: 10.1016/S0361-9230(99)00037-4 PubMedCrossRefGoogle Scholar
  105. Pesold C, Impagnatiello F, Pisu MG, Uzunov DP, Costa E, Guidotti A, Caruncho HJ (1998) Reelin is preferentially expressed in neurons synthesizing gamma-aminobutyric acid in cortex and hippocampus of adult rats. Proc Natl Acad Sci U S A 95(6):3221–3226. doi: 10.1073/pnas.95.6.3221 PubMedPubMedCentralCrossRefGoogle Scholar
  106. Piccin D, Morshead CM (2011) Wnt signaling regulates symmetry of division of neural stem cells in the adult brain and in response to injury. Stem Cells 29(3):528–538. doi: 10.1002/stem.589 PubMedCrossRefGoogle Scholar
  107. Piccin D, Tufford A, Morshead CM (2014) Neural stem and progenitor cells in the aged subependyma are activated by the young niche. Neurobiol Aging 35(7):1669–1679. doi: 10.1016/j.neurobiolaging.2014.01.026 PubMedCrossRefGoogle Scholar
  108. Plane JM, Liu R, Wang TW, Silverstein FS, Parent JM (2004) Neonatal hypoxic-ischemic injury increases forebrain subventricular zone neurogenesis in the mouse. Neurobiol Dis 16(3):585–595. doi: 10.1016/j.nbd.2004.04.003 PubMedCrossRefGoogle Scholar
  109. Plane JM, Andjelkovic AV, Keep RF, Parent JM (2010) Intact and injured endothelial cells differentially modulate postnatal murine forebrain neural stem cells. Neurobiol Dis 37(1):218–227. doi: 10.1016/j.nbd.2009.10.008.INTACT PubMedCrossRefGoogle Scholar
  110. Redmond KJ, Mark Mahone E, Terezakis S, Ishaq O, Ford E, McNutt T et al (2013) Association between radiation dose to neuronal progenitor cell niches and temporal lobes and performance on neuropsychological testing in children: a prospective study. Neuro-Oncology 15(3):360–369. doi: 10.1093/neuonc/nos303 PubMedPubMedCentralCrossRefGoogle Scholar
  111. Reeve RL, Yammine SZ, De Veale B, van der Kooy D (2016) Targeted activation of primitive neural stem cells in the mouse brain. Eur J Neurosci 43. doi:  10.1111/ejn.13228
  112. Reynolds BA, Weiss S (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255(5052):1707–1710PubMedCrossRefGoogle Scholar
  113. Ribeiro Xavier AL, Kress BT, Goldman SA, Lacerda de Menezes JR, Nedergaard M (2015) A distinct population of microglia supports adult neurogenesis in the Subventricular zone. J Neurosci 35(34):11848–11861. doi: 10.1523/JNEUROSCI.1217-15.2015 PubMedPubMedCentralCrossRefGoogle Scholar
  114. Riquelme PA, Drapeau E, Doetsch F (2008) Brain micro-ecologies: neural stem cell niches in the adult mammalian brain. Philos Trans R Soc Lond B 363(1489):123–137. doi: 10.1098/rstb.2006.2016 CrossRefGoogle Scholar
  115. Rola R, Raber J, Rizk A, Otsuka S, Vandenberg SR, Morhardt DR, Fike JR (2004) Radiation-induced impairment of hippocampal neurogenesis is associated with cognitive deficits in young mice. Exp Neurol 188(2):316–330. doi: 10.1016/j.expneurol.2004.05.005 PubMedCrossRefGoogle Scholar
  116. Romanko MJ, Rothstein RP, Levison SW (2004) Neural stem cells in the subventricular zone are resilient to hypoxia/ischemia whereas progenitors are vulnerable. J Cereb Blood Flow Metab 24(7):814–825. doi: 10.1097/01.WCB.0000123906.17746.00 PubMedCrossRefGoogle Scholar
  117. Rothstein RP, Levison SW (2002) Damage to the choroid plexus, ependyma and subependyma as a consequence of perinatal hypoxia/ischemia. Dev Neurosci 24(5):426–436. doi: 10.1159/000069052 PubMedCrossRefGoogle Scholar
  118. Roughton K, Kalm M, Blomgren K (2012) Sex-dependent differences in behavior and hippocampal neurogenesis after irradiation to the young mouse brain. Eur J Neurosci 36(6):2763–2772. doi: 10.1111/j.1460-9568.2012.08197.x PubMedCrossRefGoogle Scholar
  119. Rumajogee P, Bregman T, Miller SP, Yager JY, Fehlings MG (2016) Rodent hypoxia-ischemia models for cerebral palsy research: A systematic review. Front Neurol 7. doi:  10.3389/fneur.2016.00057
  120. Ryu JR, Hong CJ, Kim JY, Kim E, Sun W (2016) Control of adult neurogenesis by programmed cell death in the mammalian brain. Mol Brain :1–20. doi:  10.1186/s13041-016-0224-4
  121. Sachewsky N, Leeder R, Xu W, Rose KL, Yu F, Van Der Kooy D, Morshead CM (2014) Primitive neural stem cells in the adult mammalian brain give rise to GFAP-expressing neural stem cells. Stem Cell Rep 2(6):810–824. doi: 10.1016/j.stemcr.2014.04.008 CrossRefGoogle Scholar
  122. Sawamoto K, Wichterle H, Gonzalez-Perez O, Cholfin JA, Yamada M, Spassky N et al (2006) New neurons follow the flow of cerebrospinal fluid in the adult brain. Science 311(5761):629–632. doi: 10.1126/science.1119133 PubMedCrossRefGoogle Scholar
  123. Seib DRM, Martin-Villalba A (2015) Neurogenesis in the normal ageing hippocampus: a mini-review. Gerontology 61(4):327–335. doi: 10.1159/000368575 PubMedCrossRefGoogle Scholar
  124. Seib DRM, Corsini NS, Ellwanger K, Plaas C, Mateos A, Pitzer C et al (2013) Loss of Dickkopf-1 restores neurogenesis in old age and counteracts cognitive decline. Cell Stem Cell 12:204–214. doi: 10.1016/j.stem.2012.11.010 PubMedCrossRefGoogle Scholar
  125. Shetty AK, Hattiangady B, Shetty GA (2005) Stem/progenitor cell proliferation factors FGF-2, IGF-1, and VEGF exhibit early decline during the course of aging in the hippocampus: role of astrocytes. Glia 51(3):173–186. doi: 10.1002/glia.20187 PubMedCrossRefGoogle Scholar
  126. Shigemoto-Mogami Y, Hoshikawa K, Goldman JE, Sekino Y, Sato K (2014) Microglia enhance neurogenesis and oligodendrogenesis in the early postnatal subventricular zone. J Neurosci 34(6):2231–2243. doi: 10.1523/JNEUROSCI.1619-13.2014 PubMedPubMedCentralCrossRefGoogle Scholar
  127. Shingo T, Gregg C, Enwere E, Fujikawa H, Hassam R, Geary C et al (2003) Pregnancy-stimulated_neurogene.PDF. Science 299:117–120PubMedCrossRefGoogle Scholar
  128. Sibbe M, Förster E, Basak O, Taylor V, Frotscher M (2009) Reelin and Notch1 cooperate in the development of the dentate gyrus. J Neurosci 29(26):8578–8585. doi: 10.1523/JNEUROSCI.0958-09.2009 PubMedCrossRefGoogle Scholar
  129. Sierra A, Encinas JM, Deudero JJ, Chancey JH, Enikolopov G, Overstreet-Wadiche LS et al (2010) Microglia shape adult hippocampal neurogenesis through apoptosis-couple phagocytosis. Cell Stem Cell 7(4):483–495. doi: 10.1016/j.stem.2010.08.014.Microglia PubMedPubMedCentralCrossRefGoogle Scholar
  130. Skoff RP, Bessert DA, Barks JDE, Song D, Cerghet M, Silverstein FS (2001) Hypoxic-ischemic injury results in acute disruption of myelin gene expression and death of oligodendroglial precursors in neonatal mice. Int J Dev Neurosci 19(2):197–208. doi: 10.1016/S0736-5748(00)00075-7 PubMedCrossRefGoogle Scholar
  131. Solano Fonseca R, Mahesula S, Apple D, Raghunathan R, Dugan A, Cardona A et al (2016) Neurogenic niche microglia undergo positional remodeling and progressive activation contributing to age-associated reductions in neurogenesis. Stem Cells Dev 25(7):542–555. doi: 10.1089/scd.2015.0319 PubMedPubMedCentralCrossRefGoogle Scholar
  132. Sugiura S, Kitagawa K, Tanaka S, Todo K, Omura-Matsuoka E, Sasaki T et al (2005) Adenovirus-mediated gene transfer of heparin-binding epidermal growth factor-like growth factor enhances neurogenesis and angiogenesis after focal cerebral ischemia in rats. Stroke 36(4):859–864. doi: 10.1161/01.STR.0000158905.22871.95 PubMedCrossRefGoogle Scholar
  133. Sun Y, Calvert JW, Zhang JH (2005) Neonatal hypoxia/ischemia is associated with decreased inflammatory mediators after erythropoietin administration. Stroke 36(8):1672–1678. doi: 10.1161/01.STR.0000173406.04891.8c PubMedCrossRefGoogle Scholar
  134. Tanapat P, Hastings NB, Reeves AJ, Gould E (1999) Estrogen stimulates a transient increase in the number of new neurons in the dentate gyrus of the adult female rat. J Neurosci 19(14):5792–5801. doi: 10.1016/j.brainresrev.2007.06.011 PubMedGoogle Scholar
  135. Tao Y, Ma L, Liao Z, Le Q, Yu J, Liu X et al (2015) Astroglial β-Arrestin1-mediated nuclear signaling regulates the expansion of neural precursor cells in adult hippocampus. Sci Rep 5(April):15506. doi: 10.1038/srep15506 PubMedPubMedCentralCrossRefGoogle Scholar
  136. Tatar C, Bessert D, Tse H, Skoff RP (2013) Determinants of central nervous system adult neurogenesis are sex, hormones, mouse strain, age, and brain region. Glia 61(2):192–209. doi: 10.1002/glia.22426 PubMedCrossRefGoogle Scholar
  137. Tavazoie M, Van der Veken L, Silva-Vargas V, Louissaint M, Colonna L, Zaidi B et al (2008) A specialized vascular niche for adult neural stem cells. Cell Stem Cell 3(3):279–288. doi: 10.1016/j.stem.2008.07.025 PubMedCrossRefGoogle Scholar
  138. Thompson SA (1982) Localization of immunoreactive prolactin in ependyma and circumventricular organs of rat brain. Cell Tissue Res 225(1):79–93. doi: 10.1007/BF00216220 PubMedCrossRefGoogle Scholar
  139. Thored P, Wood J, Arvidsson A, Cammenga J, Kokaia Z, Lindvall O (2007) Long-term neuroblast migration along blood vessels in an area with transient angiogenesis and increased vascularization after stroke. Stroke 38(11):3032–3039. doi: 10.1161/STROKEAHA.107.488445 PubMedCrossRefGoogle Scholar
  140. Toesca A, Geloso MC, Mongiovì AM, Furno A, Schiattarella A, Michetti F, Corvino V (2016) Trimethyltin modulates Reelin expression and endogenous neurogenesis in the hippocampus of developing rats. Neurochem Res 41(7):1559–1569. doi: 10.1007/s11064-016-1869-1 PubMedCrossRefGoogle Scholar
  141. Tonning Olsson I, Perrin S, Lundgren J, Hjorth L, Johanson A (2014) Long-term cognitive sequelae after pediatric brain tumor related to medical risk factors, age, and sex. Pediatr Neurol 51(4):515–521. doi: 10.1016/j.pediatrneurol.2014.06.011 PubMedCrossRefGoogle Scholar
  142. Torner L, Karg S, Blume A, Kandasamy M, Kuhn H-G, Winkler J et al (2009) Prolactin prevents chronic stress-induced decrease of adult hippocampal neurogenesis and promotes neuronal fate. J Neurosci 29(6):1826–1833. doi: 10.1523/JNEUROSCI.3178-08.2009 PubMedCrossRefGoogle Scholar
  143. Tramontin AD, García-verdugo JM, Lim DA, Alvarez-buylla A (2003) Postnatal development of radial glia and the ventricular zone ( VZ ): a continuum of the neural stem cell compartment. Cereb Cortex 13(6):580–587PubMedCrossRefGoogle Scholar
  144. Tropepe V, Craig CG, Morshead CM, van der Kooy D (1997) Transforming growth factor-alpha null and senescent mice show decreased neural progenitor cell proliferation in the forebrain subependyma.J Neurosci 17:7850–7859Google Scholar
  145. van Praag H, Kempermann G, Gage FH (1999) Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci 2(3):266–270. doi: 10.1038/6368 PubMedCrossRefGoogle Scholar
  146. Villeda SA, Luo J, Mosher KI, Zou B, Britschgi M, Stan TM, … Galasko DR (2012) The aging systemic milieu negatively regulates neurogenesis and cognitive function. 477(7362):90–94. doi:  10.1038/nature10357.The
  147. Waldron J, McCourty A, Lecanu L (2010a) Aging differentially affects male and female neural stem cell neurogenic properties. Stem Cells Cloning 3(1):119–127. doi: 10.2147/SCCAA.S13035 PubMedPubMedCentralGoogle Scholar
  148. Waldron J, McCourty A, Lecanu L (2010b) Neural stem cell sex dimorphism in aromatase (CYP19) expression: a basis for differential neural fate. Stem Cells Cloning 3:175–182. doi: 10.2147/SCCAA.S15200 PubMedPubMedCentralGoogle Scholar
  149. Walton RM (2012) Postnatal Neurogenesis. Vet Pathol 49(1):155–165. doi: 10.1177/0300985811414035 PubMedCrossRefGoogle Scholar
  150. Wiltrout C, Lang B, Yan Y, Dempsey RJ, Vemuganti R (2007) Repairing brain after stroke: a review on post-ischemic neurogenesis. Neurochem Int 50(7–8):1028–1041. doi: 10.1016/j.neuint.2007.04.011 PubMedCrossRefGoogle Scholar
  151. Yan YP, Sailor KA, Vemuganti R, Dempsey RJ (2006) Insulin-like growth factor-1 is an endogenous mediator of focal ischemia-induced neural progenitor proliferation. Eur J Neurosci 24(1):45–54. doi: 10.1111/j.1460-9568.2006.04872.x PubMedCrossRefGoogle Scholar
  152. Yang Z, Levison SW (2006) Hypoxia/ischemia expands the regenerative capacity of progenitors in the perinatal subventricular zone. Neuroscience 139(2):555–564. doi: 10.1016/j.neuroscience.2005.12.059 PubMedCrossRefGoogle Scholar
  153. Yang Z, Levison SW (2007) Perinatal hypoxic/ischemic brain injury induces persistent production of striatal neurons from subventricular zone progenitors. Dev Neurosci 29(4–5):331–340. doi: 10.1159/000105474 PubMedCrossRefGoogle Scholar
  154. Yau SY, Gil-Mohapel J, Christie BR, So KF (2014) Physical exercise-induced adult neurogenesis: a good strategy to prevent cognitive decline in neurodegenerative diseases? Biomed Res Int 2014(Figure 1). doi: 10.1155/2014/403120
  155. Yoshimura S, Takagi Y, Harada J, Teramoto T, Thomas SS, Waeber C et al (2001) FGF-2 regulation of neurogenesis in adult hippocampus after brain injury. Proc Natl Acad Sci U S A 98(10):5874–5879. doi: 10.1073/pnas.101034998 PubMedPubMedCentralCrossRefGoogle Scholar
  156. Zhang J, Jiao J (2015) Molecular biomarkers for embryonic and adult neural stem cell and neurogenesis. Biomed Res Int. doi: 10.1155/2015/727542
  157. Zhang R, Zhang Z, Wang L, Wang Y, Gousev A, Zhang L et al (2004) Activated neural stem cells contribute to stroke-induced neurogenesis and neuroblast migration toward the infarct boundary in adult rats. J Cereb Blood Flow Metab 24(4):441–448. doi: 10.1097/00004647-200404000-00009
  158. Zhang J, Moats-Staats BM, Ye P, D’Ercole AJ (2007) Expression of insulin-like growth factor system genes during the early postnatal neurogenesis in the mouse hippocampus. J Neurosci Res 4(164):1618–1627. doi: 10.1126/scisignal.2001449.Engineering CrossRefGoogle Scholar
  159. Zhang RL, Chopp M, Roberts C, Liu X, Wei M, Nejad-Davarani SP et al (2014) Stroke increases neural stem cells and angiogenesis in the neurogenic niche of the adult mouse. PLoS ONE 9(12):1–15. doi: 10.1371/journal.pone.0113972 Google Scholar
  160. Ziegler AN, Levison SW, Wood TL (2014) Insulin and IGF receptor signalling in neural-stem-cell homeostasis. Nat Publ Group 11(3):1–10. doi: 10.1038/nrendo.2014.208 Google Scholar

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© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Institute of Medical ScienceUniversity of TorontoTorontoCanada
  2. 2.Department of SurgeryUniversity of TorontoTorontoCanada

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