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Adult Neurogenesis in the Subventricular Zone and Its Regulation After Ischemic Stroke: Implications for Therapeutic Approaches

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Abstract

Adult neurogenesis in the subventricular zone is a topic of intense research, since it has vast implications for the fundamental understanding of the neurobiology of the brain and its potential to being harnessed for therapy in various neurological disorders. Investigation of adult neurogenesis has been complicated by the difficulties with characterization of neural stem cells in vivo. However, recent single-cell transcriptomic studies provide more detailed information on marker expression in neural stem cells and their neuronal lineage, which hopefully will result in a more unified discussion. Regulation of the multiple biological steps in adult neurogenesis comprises intrinsic mechanisms as well as extrinsic factors which together orchestrate the process. In this review, we describe the regulating factors and their cellular sources in the physiological condition and provide an overview of the regulating factors mediating stroke-induced stimulation of neurogenesis in the subventricular zone. While there is ongoing debate about the longevity of active post-natal neurogenesis in humans, the subventricular zone has the capacity to upregulate neurogenesis in response to ischemic stroke. Though, the stroke-induced neurogenesis in humans does not seem to translate into adequate functional recovery, which opens discussion about potential treatment strategies to harness this neuroregenerative response. Various therapeutic approaches are explored in preclinical and clinical studies to target endogenous neurogenesis of which some are discussed in this review.

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References

  1. 1.

    Altman J. Autoradiographic investigation of cell proliferation in the brains of rats and cats. Anat Rec. 1963;145:573–91.

  2. 2.

    Reynolds BA, Weiss S. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science. 1992;255(5052):1707–10.

  3. 3.

    Lois C, Alvarez-Buylla A. Long-distance neuronal migration in the adult mammalian brain. Science. 1994;264(5162):1145–8.

  4. 4.

    Eriksson PS, Perfilieva E, Bjork-Eriksson T, Alborn AM, Nordborg C, Peterson DA, et al. Neurogenesis in the adult human hippocampus. Nat Med. 1998;4(11):1313–7. https://doi.org/10.1038/3305.

  5. 5.

    Sohur US, Emsley JG, Mitchell BD, Macklis JD. Adult neurogenesis and cellular brain repair with neural progenitors, precursors and stem cells. Philos Trans R Soc Lond Ser B Biol Sci. 2006;361(1473):1477–97. https://doi.org/10.1098/rstb.2006.1887.

  6. 6.

    Lledo PM, Alonso M, Grubb MS. Adult neurogenesis and functional plasticity in neuronal circuits. Nat Rev Neurosci. 2006;7(3):179–93. https://doi.org/10.1038/nrn1867.

  7. 7.

    Ming GL, Song H. Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron. 2011;70(4):687–702. https://doi.org/10.1016/j.neuron.2011.05.001.

  8. 8.

    Faigle R, Song H. Signaling mechanisms regulating adult neural stem cells and neurogenesis. Biochim Biophys Acta. 2013;1830(2):2435–48. https://doi.org/10.1016/j.bbagen.2012.09.002.

  9. 9.

    Navarro Quiroz E, Navarro Quiroz R, Ahmad M, Gomez Escorcia L, Villarreal JL, Fernandez Ponce C, et al. Cell signaling in neuronal stem cells. Cells. 2018;7(7):75. https://doi.org/10.3390/cells7070075.

  10. 10.

    Hankey GJ. Stroke. Lancet. 2017;389(10069):641–54. https://doi.org/10.1016/S0140-6736(16)30962-X.

  11. 11.

    Brouns R, De Deyn PP. The complexity of neurobiological processes in acute ischemic stroke. Clin Neurol Neurosurg. 2009;111(6):483–95. https://doi.org/10.1016/j.clineuro.2009.04.001.

  12. 12.

    Lambertsen KL, Finsen B, Clausen BH. Post-stroke inflammation-target or tool for therapy? Acta Neuropathol. 2018;137(5):693–714. https://doi.org/10.1007/s00401-018-1930-z.

  13. 13.

    Marques BL, Carvalho GA, Freitas EMM, Chiareli RA, Barbosa TG, Di Araujo AGP, et al. The role of neurogenesis in neurorepair after ischemic stroke. Semin Cell Dev Biol. 2019;S1084-9521(18)30251-9. https://doi.org/10.1016/j.semcdb.2018.12.003.

  14. 14.

    Belluzzi O, Benedusi M, Ackman J, LoTurco JJ. Electrophysiological differentiation of new neurons in the olfactory bulb. J Neurosci. 2003;23(32):10411–8.

  15. 15.

    Arisi GM, Foresti ML, Mukherjee S, Shapiro LA. The role of olfactory stimulus in adult mammalian neurogenesis. Behav Brain Res. 2012;227(2):356–62. https://doi.org/10.1016/j.bbr.2011.03.050.

  16. 16.

    Doetsch F, Caille I, Lim DA, Garcia-Verdugo JM, Alvarez-Buylla A. Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell. 1999;97(6):703–16.

  17. 17.

    Kriegstein A, Alvarez-Buylla A. The glial nature of embryonic and adult neural stem cells. Annu Rev Neurosci. 2009;32:149–84. https://doi.org/10.1146/annurev.neuro.051508.135600.

  18. 18.

    Mirzadeh Z, Han YG, Soriano-Navarro M, Garcia-Verdugo JM, Alvarez-Buylla A. Cilia organize ependymal planar polarity. J Neurosci. 2010;30(7):2600–10. https://doi.org/10.1523/JNEUROSCI.3744-09.2010.

  19. 19.

    Mirzadeh Z, Merkle FT, Soriano-Navarro M, Garcia-Verdugo JM, Alvarez-Buylla A. Neural stem cells confer unique pinwheel architecture to the ventricular surface in neurogenic regions of the adult brain. Cell Stem Cell. 2008;3(3):265–78. https://doi.org/10.1016/j.stem.2008.07.004.

  20. 20.

    Zhao C, Deng W, Gage FH. Mechanisms and functional implications of adult neurogenesis. Cell. 2008;132(4):645–60. https://doi.org/10.1016/j.cell.2008.01.033.

  21. 21.

    Llorens-Bobadilla E, Zhao S, Baser A, Saiz-Castro G, Zwadlo K, Martin-Villalba A. Single-cell transcriptomics reveals a population of dormant neural stem cells that become activated upon brain injury. Cell Stem Cell. 2015;17(3):329–40. https://doi.org/10.1016/j.stem.2015.07.002.

  22. 22.

    Dulken BW, Leeman DS, Boutet SC, Hebestreit K, Brunet A. Single-cell transcriptomic analysis defines heterogeneity and transcriptional dynamics in the adult neural stem cell lineage. Cell Rep. 2017;18(3):777–90. https://doi.org/10.1016/j.celrep.2016.12.060.

  23. 23.

    Shah PT, Stratton JA, Stykel MG, Abbasi S, Sharma S, Mayr KA, et al. Single-cell transcriptomics and fate mapping of ependymal cells reveals an absence of neural stem cell function. Cell. 2018;173(4):1045–57 e9. https://doi.org/10.1016/j.cell.2018.03.063.

  24. 24.

    Ahn S, Joyner AL. In vivo analysis of quiescent adult neural stem cells responding to Sonic hedgehog. Nature. 2005;437(7060):894–7. https://doi.org/10.1038/nature03994.

  25. 25.

    Bonaguidi MA, Wheeler MA, Shapiro JS, Stadel RP, Sun GJ, Ming GL, et al. In vivo clonal analysis reveals self-renewing and multipotent adult neural stem cell characteristics. Cell. 2011;145(7):1142–55. https://doi.org/10.1016/j.cell.2011.05.024.

  26. 26.

    Merkle FT, Mirzadeh Z, Alvarez-Buylla A. Mosaic organization of neural stem cells in the adult brain. Science. 2007;317(5836):381–4. https://doi.org/10.1126/science.1144914.

  27. 27.

    Beckervordersandforth R, Tripathi P, Ninkovic J, Bayam E, Lepier A, Stempfhuber B, et al. In vivo fate mapping and expression analysis reveals molecular hallmarks of prospectively isolated adult neural stem cells. Cell Stem Cell. 2010;7(6):744–58. https://doi.org/10.1016/j.stem.2010.11.017.

  28. 28.

    Codega P, Silva-Vargas V, Paul A, Maldonado-Soto AR, Deleo AM, Pastrana E, et al. Prospective identification and purification of quiescent adult neural stem cells from their in vivo niche. Neuron. 2014;82(3):545–59. https://doi.org/10.1016/j.neuron.2014.02.039.

  29. 29.

    Suh Y, Obernier K, Holzl-Wenig G, Mandl C, Herrmann A, Worner K, et al. Interaction between DLX2 and EGFR regulates proliferation and neurogenesis of SVZ precursors. Mol Cell Neurosci. 2009;42(4):308–14. https://doi.org/10.1016/j.mcn.2009.08.003.

  30. 30.

    Hsieh J. Orchestrating transcriptional control of adult neurogenesis. Genes Dev. 2012;26(10):1010–21. https://doi.org/10.1101/gad.187336.112.

  31. 31.

    Lim DA, Alvarez-Buylla A. The adult ventricular-subventricular zone (V-SVZ) and olfactory bulb (OB) neurogenesis. Cold Spring Harb Perspect Biol. 2016;8(5). https://doi.org/10.1101/cshperspect.a018820.

  32. 32.

    Lepousez G, Valley MT, Lledo PM. The impact of adult neurogenesis on olfactory bulb circuits and computations. Annu Rev Physiol. 2013;75:339–63. https://doi.org/10.1146/annurev-physiol-030212-183731.

  33. 33.

    Gage FH. Mammalian neural stem cells. Science. 2000;287(5457):1433–8.

  34. 34.

    Braun SM, Jessberger S. Adult neurogenesis: mechanisms and functional significance. Development. 2014;141(10):1983–6. https://doi.org/10.1242/dev.104596.

  35. 35.

    Ma DK, Kim WR, Ming GL, Song H. Activity-dependent extrinsic regulation of adult olfactory bulb and hippocampal neurogenesis. Ann N Y Acad Sci. 2009;1170:664–73. https://doi.org/10.1111/j.1749-6632.2009.04373.x.

  36. 36.

    Lin R, Cai J, Kenyon L, Iozzo R, Rosenwasser R, Iacovitti L. Systemic factors trigger vasculature cells to drive notch signaling and neurogenesis in neural stem cells in the adult brain. Stem Cells. 2019;37(3):395–406. https://doi.org/10.1002/stem.2947.

  37. 37.

    Katsimpardi L, Lledo PM. Regulation of neurogenesis in the adult and aging brain. Curr Opin Neurobiol. 2018;53:131–8. https://doi.org/10.1016/j.conb.2018.07.006.

  38. 38.

    Bjornsson CS, Apostolopoulou M, Tian Y, Temple S. It takes a village: constructing the neurogenic niche. Dev Cell. 2015;32(4):435–46. https://doi.org/10.1016/j.devcel.2015.01.010.

  39. 39.

    Falk S, Gotz M. Glial control of neurogenesis. Curr Opin Neurobiol. 2017;47:188–95. https://doi.org/10.1016/j.conb.2017.10.025.

  40. 40.

    Gajera CR, Emich H, Lioubinski O, Christ A, Beckervordersandforth-Bonk R, Yoshikawa K, et al. LRP2 in ependymal cells regulates BMP signaling in the adult neurogenic niche. J Cell Sci. 2010;123(Pt 11):1922–30. https://doi.org/10.1242/jcs.065912.

  41. 41.

    Carlen M, Meletis K, Goritz C, Darsalia V, Evergren E, Tanigaki K, et al. Forebrain ependymal cells are Notch-dependent and generate neuroblasts and astrocytes after stroke. Nat Neurosci. 2009;12(3):259–67. https://doi.org/10.1038/nn.2268.

  42. 42.

    Luo Y, Coskun V, Liang A, Yu J, Cheng L, Ge W, et al. Single-cell transcriptome analyses reveal signals to activate dormant neural stem cells. Cell. 2015;161(5):1175–86. https://doi.org/10.1016/j.cell.2015.04.001.

  43. 43.

    Ramirez-Castillejo C, Sanchez-Sanchez F, Andreu-Agullo C, Ferron SR, Aroca-Aguilar JD, Sanchez P, et al. Pigment epithelium-derived factor is a niche signal for neural stem cell renewal. Nat Neurosci. 2006;9(3):331–9. https://doi.org/10.1038/nn1657.

  44. 44.

    Kokovay E, Goderie S, Wang Y, Lotz S, Lin G, Sun Y, et al. Adult SVZ lineage cells home to and leave the vascular niche via differential responses to SDF1/CXCR4 signaling. Cell Stem Cell. 2010;7(2):163–73. https://doi.org/10.1016/j.stem.2010.05.019.

  45. 45.

    Lim DA, Tramontin AD, Trevejo JM, Herrera DG, Garcia-Verdugo JM, Alvarez-Buylla A. Noggin antagonizes BMP signaling to create a niche for adult neurogenesis. Neuron. 2000;28(3):713–26.

  46. 46.

    Wang DD, Bordey A. The astrocyte odyssey. Prog Neurobiol. 2008;86(4):342–67. https://doi.org/10.1016/j.pneurobio.2008.09.015.

  47. 47.

    Barkho BZ, Song H, Aimone JB, Smrt RD, Kuwabara T, Nakashima K, et al. Identification of astrocyte-expressed factors that modulate neural stem/progenitor cell differentiation. Stem Cells Dev. 2006;15(3):407–21. https://doi.org/10.1089/scd.2006.15.407.

  48. 48.

    Hitoshi S, Alexson T, Tropepe V, Donoviel D, Elia AJ, Nye JS, et al. Notch pathway molecules are essential for the maintenance, but not the generation, of mammalian neural stem cells. Genes Dev. 2002;16(7):846–58. https://doi.org/10.1101/gad.975202.

  49. 49.

    Platel JC, Dave KA, Gordon V, Lacar B, Rubio ME, Bordey A. NMDA receptors activated by subventricular zone astrocytic glutamate are critical for neuroblast survival prior to entering a synaptic network. Neuron. 2010;65(6):859–72. https://doi.org/10.1016/j.neuron.2010.03.009.

  50. 50.

    Shetty AK, Hattiangady B, Shetty GA. 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. 2005;51(3):173–86. https://doi.org/10.1002/glia.20187.

  51. 51.

    Song H, Stevens CF, Gage FH. Astroglia induce neurogenesis from adult neural stem cells. Nature. 2002;417(6884):39–44. https://doi.org/10.1038/417039a.

  52. 52.

    Xiao Z, Kong Y, Yang S, Li M, Wen J, Li L. Upregulation of Flk-1 by bFGF via the ERK pathway is essential for VEGF-mediated promotion of neural stem cell proliferation. Cell Res. 2007;17(1):73–9. https://doi.org/10.1038/sj.cr.7310126.

  53. 53.

    Basak O, Giachino C, Fiorini E, Macdonald HR, Taylor V. Neurogenic subventricular zone stem/progenitor cells are Notch1-dependent in their active but not quiescent state. J Neurosci. 2012;32(16):5654–66. https://doi.org/10.1523/JNEUROSCI.0455-12.2012.

  54. 54.

    Ferron SR, Charalambous M, Radford E, McEwen K, Wildner H, Hind E, et al. Postnatal loss of Dlk1 imprinting in stem cells and niche astrocytes regulates neurogenesis. Nature. 2011;475(7356):381–5. https://doi.org/10.1038/nature10229.

  55. 55.

    Nyfeler Y, Kirch RD, Mantei N, Leone DP, Radtke F, Suter U, et al. Jagged1 signals in the postnatal subventricular zone are required for neural stem cell self-renewal. EMBO J. 2005;24(19):3504–15. https://doi.org/10.1038/sj.emboj.7600816.

  56. 56.

    Yu JM, Kim JH, Song GS, Jung JS. Increase in proliferation and differentiation of neural progenitor cells isolated from postnatal and adult mice brain by Wnt-3a and Wnt-5a. Mol Cell Biochem. 2006;288(1–2):17–28. https://doi.org/10.1007/s11010-005-9113-3.

  57. 57.

    Adachi K, Mirzadeh Z, Sakaguchi M, Yamashita T, Nikolcheva T, Gotoh Y, et al. Beta-catenin signaling promotes proliferation of progenitor cells in the adult mouse subventricular zone. Stem Cells. 2007;25(11):2827–36. https://doi.org/10.1634/stemcells.2007-0177.

  58. 58.

    Moreno-Estelles M, Gonzalez-Gomez P, Hortiguela R, Diaz-Moreno M, San Emeterio J, Carvalho AL, et al. Symmetric expansion of neural stem cells from the adult olfactory bulb is driven by astrocytes via WNT7A. Stem Cells. 2012;30(12):2796–809. https://doi.org/10.1002/stem.1243.

  59. 59.

    Kowanetz M, Valcourt U, Bergstrom R, Heldin CH, Moustakas A. Id2 and Id3 define the potency of cell proliferation and differentiation responses to transforming growth factor beta and bone morphogenetic protein. Mol Cell Biol. 2004;24(10):4241–54.

  60. 60.

    Colak D, Mori T, Brill MS, Pfeifer A, Falk S, Deng C, et al. Adult neurogenesis requires Smad4-mediated bone morphogenic protein signaling in stem cells. J Neurosci. 2008;28(2):434–46. https://doi.org/10.1523/JNEUROSCI.4374-07.2008.

  61. 61.

    Peretto P, Dati C, De Marchis S, Kim HH, Ukhanova M, Fasolo A, et al. Expression of the secreted factors noggin and bone morphogenetic proteins in the subependymal layer and olfactory bulb of the adult mouse brain. Neuroscience. 2004;128(4):685–96. https://doi.org/10.1016/j.neuroscience.2004.06.053.

  62. 62.

    Jiao J, Chen DF. Induction of neurogenesis in nonconventional neurogenic regions of the adult central nervous system by niche astrocyte-produced signals. Stem Cells. 2008;26(5):1221–30. https://doi.org/10.1634/stemcells.2007-0513.

  63. 63.

    Bowen KK, Dempsey RJ, Vemuganti R. Adult interleukin-6 knockout mice show compromised neurogenesis. Neuroreport. 2011;22(3):126–30. https://doi.org/10.1097/WNR.0b013e3283430a44.

  64. 64.

    Schanzer A, Wachs FP, Wilhelm D, Acker T, Cooper-Kuhn C, Beck H, et al. Direct stimulation of adult neural stem cells in vitro and neurogenesis in vivo by vascular endothelial growth factor. Brain Pathol. 2004;14(3):237–48.

  65. 65.

    Emsley JG, Hagg T. Endogenous and exogenous ciliary neurotrophic factor enhances forebrain neurogenesis in adult mice. Exp Neurol. 2003;183(2):298–310.

  66. 66.

    Balordi F, Fishell G. Hedgehog signaling in the subventricular zone is required for both the maintenance of stem cells and the migration of newborn neurons. J Neurosci. 2007;27(22):5936–47. https://doi.org/10.1523/JNEUROSCI.1040-07.2007.

  67. 67.

    Angot E, Loulier K, Nguyen-Ba-Charvet KT, Gadeau AP, Ruat M, Traiffort E. Chemoattractive activity of sonic hedgehog in the adult subventricular zone modulates the number of neural precursors reaching the olfactory bulb. Stem Cells. 2008;26(9):2311–20. https://doi.org/10.1634/stemcells.2008-0297.

  68. 68.

    Zheng W, Nowakowski RS, Vaccarino FM. Fibroblast growth factor 2 is required for maintaining the neural stem cell pool in the mouse brain subventricular zone. Dev Neurosci. 2004;26(2–4):181–96. https://doi.org/10.1159/000082136.

  69. 69.

    Ekdahl CT, Kokaia Z, Lindvall O. Brain inflammation and adult neurogenesis: the dual role of microglia. Neuroscience. 2009;158(3):1021–9. https://doi.org/10.1016/j.neuroscience.2008.06.052.

  70. 70.

    Xiong XY, Liu L, Yang QW. Functions and mechanisms of microglia/macrophages in neuroinflammation and neurogenesis after stroke. Prog Neurobiol. 2016;142:23–44. https://doi.org/10.1016/j.pneurobio.2016.05.001.

  71. 71.

    Qin C, Zhou LQ, Ma XT, Hu ZW, Yang S, Chen M, et al. Dual functions of microglia in ischemic stroke. Neurosci Bull. 2019:1–13. https://doi.org/10.1007/s12264-019-00388-3.

  72. 72.

    Harry GJ. Microglia during development and aging. Pharmacol Ther. 2013;139(3):313–26. https://doi.org/10.1016/j.pharmthera.2013.04.013.

  73. 73.

    Fuster-Matanzo A, Llorens-Martin M, Hernandez F, Avila J. Role of neuroinflammation in adult neurogenesis and Alzheimer disease: therapeutic approaches. Mediat Inflamm. 2013;2013:260925. https://doi.org/10.1155/2013/260925.

  74. 74.

    Sierra A, Encinas JM, Deudero JJ, Chancey JH, Enikolopov G, Overstreet-Wadiche LS, et al. Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis. Cell Stem Cell. 2010;7(4):483–95. https://doi.org/10.1016/j.stem.2010.08.014.

  75. 75.

    Morrens J, Van Den Broeck W, Kempermann G. Glial cells in adult neurogenesis. Glia. 2012;60(2):159–74. https://doi.org/10.1002/glia.21247.

  76. 76.

    Su P, Zhang J, Zhao F, Aschner M, Chen J, Luo W. The interaction between microglia and neural stem/precursor cells. Brain Res Bull. 2014;109:32–8. https://doi.org/10.1016/j.brainresbull.2014.09.005.

  77. 77.

    Lira-Diaz E, Gonzalez-Perez O. Emerging roles of microglia cells in the regulation of adult neural stem cells. Neuroimmunol Neuroinflamm. 2016;3:204–6. https://doi.org/10.20517/2347-8659.2016.32.

  78. 78.

    Paez-Gonzalez P, Asrican B, Rodriguez E, Kuo CT. Identification of distinct ChAT(+) neurons and activity-dependent control of postnatal SVZ neurogenesis. Nat Neurosci. 2014;17(7):934–42. https://doi.org/10.1038/nn.3734.

  79. 79.

    Tong CK, Chen J, Cebrian-Silla A, Mirzadeh Z, Obernier K, Guinto CD, et al. Axonal control of the adult neural stem cell niche. Cell Stem Cell. 2014;14(4):500–11. https://doi.org/10.1016/j.stem.2014.01.014.

  80. 80.

    Torroglosa A, Murillo-Carretero M, Romero-Grimaldi C, Matarredona ER, Campos-Caro A, Estrada C. Nitric oxide decreases subventricular zone stem cell proliferation by inhibition of epidermal growth factor receptor and phosphoinositide-3-kinase/Akt pathway. Stem Cells. 2007;25(1):88–97. https://doi.org/10.1634/stemcells.2006-0131.

  81. 81.

    Romero-Grimaldi C, Moreno-Lopez B, Estrada C. Age-dependent effect of nitric oxide on subventricular zone and olfactory bulb neural precursor proliferation. J Comp Neurol. 2008;506(2):339–46. https://doi.org/10.1002/cne.21556.

  82. 82.

    Decressac M, Prestoz L, Veran J, Cantereau A, Jaber M, Gaillard A. Neuropeptide Y stimulates proliferation, migration and differentiation of neural precursors from the subventricular zone in adult mice. Neurobiol Dis. 2009;34(3):441–9. https://doi.org/10.1016/j.nbd.2009.02.017.

  83. 83.

    Thiriet N, Agasse F, Nicoleau C, Guegan C, Vallette F, Cadet JL, et al. NPY promotes chemokinesis and neurogenesis in the rat subventricular zone. J Neurochem. 2011;116(6):1018–27. https://doi.org/10.1111/j.1471-4159.2010.07154.x.

  84. 84.

    L'Episcopo F, Tirolo C, Testa N, Caniglia S, Morale MC, Deleidi M, et al. Plasticity of subventricular zone neuroprogenitors in MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model of Parkinson's disease involves cross talk between inflammatory and Wnt/beta-catenin signaling pathways: functional consequences for neuroprotection and repair. J Neurosci. 2012;32(6):2062–85. https://doi.org/10.1523/JNEUROSCI.5259-11.2012.

  85. 85.

    Baker SA, Baker KA, Hagg T. Dopaminergic nigrostriatal projections regulate neural precursor proliferation in the adult mouse subventricular zone. Eur J Neurosci. 2004;20(2):575–9. https://doi.org/10.1111/j.1460-9568.2004.03486.x.

  86. 86.

    Hoglinger GU, Rizk P, Muriel MP, Duyckaerts C, Oertel WH, Caille I, et al. Dopamine depletion impairs precursor cell proliferation in Parkinson disease. Nat Neurosci. 2004;7(7):726–35. https://doi.org/10.1038/nn1265.

  87. 87.

    Winner B, Geyer M, Couillard-Despres S, Aigner R, Bogdahn U, Aigner L, et al. Striatal deafferentation increases dopaminergic neurogenesis in the adult olfactory bulb. Exp Neurol. 2006;197(1):113–21. https://doi.org/10.1016/j.expneurol.2005.08.028.

  88. 88.

    Kippin TE, Kapur S, van der Kooy D. Dopamine specifically inhibits forebrain neural stem cell proliferation, suggesting a novel effect of antipsychotic drugs. J Neurosci. 2005;25(24):5815–23. https://doi.org/10.1523/JNEUROSCI.1120-05.2005.

  89. 89.

    Berg DA, Belnoue L, Song H, Simon A. Neurotransmitter-mediated control of neurogenesis in the adult vertebrate brain. Development. 2013;140(12):2548–61. https://doi.org/10.1242/dev.088005.

  90. 90.

    O'Keeffe GC, Tyers P, Aarsland D, Dalley JW, Barker RA, Caldwell MA. Dopamine-induced proliferation of adult neural precursor cells in the mammalian subventricular zone is mediated through EGF. Proc Natl Acad Sci U S A. 2009;106(21):8754–9. https://doi.org/10.1073/pnas.0803955106.

  91. 91.

    Lao CL, Lu CS, Chen JC. Dopamine D3 receptor activation promotes neural stem/progenitor cell proliferation through AKT and ERK1/2 pathways and expands type-B and -C cells in adult subventricular zone. Glia. 2013;61(4):475–89. https://doi.org/10.1002/glia.22449.

  92. 92.

    Yang P, Arnold SA, Habas A, Hetman M, Hagg T. Ciliary neurotrophic factor mediates dopamine D2 receptor-induced CNS neurogenesis in adult mice. J Neurosci. 2008;28(9):2231–41. https://doi.org/10.1523/JNEUROSCI.3574-07.2008.

  93. 93.

    Tavazoie M, Van der Veken L, Silva-Vargas V, Louissaint M, Colonna L, Zaidi B, et al. A specialized vascular niche for adult neural stem cells. Cell Stem Cell. 2008;3(3):279–88. https://doi.org/10.1016/j.stem.2008.07.025.

  94. 94.

    Ottone C, Krusche B, Whitby A, Clements M, Quadrato G, Pitulescu ME, et al. Direct cell-cell contact with the vascular niche maintains quiescent neural stem cells. Nat Cell Biol. 2014;16(11):1045–56. https://doi.org/10.1038/ncb3045.

  95. 95.

    Delgado AC, Ferron SR, Vicente D, Porlan E, Perez-Villalba A, Trujillo CM, et al. Endothelial NT-3 delivered by vasculature and CSF promotes quiescence of subependymal neural stem cells through nitric oxide induction. Neuron. 2014;83(3):572–85. https://doi.org/10.1016/j.neuron.2014.06.015.

  96. 96.

    Andreu-Agullo C, Morante-Redolat JM, Delgado AC, Farinas I. Vascular niche factor PEDF modulates Notch-dependent stemness in the adult subependymal zone. Nat Neurosci. 2009;12(12):1514–23. https://doi.org/10.1038/nn.2437.

  97. 97.

    Gomez-Gaviro MV, Scott CE, Sesay AK, Matheu A, Booth S, Galichet C, et al. Betacellulin promotes cell proliferation in the neural stem cell niche and stimulates neurogenesis. Proc Natl Acad Sci U S A. 2012;109(4):1317–22. https://doi.org/10.1073/pnas.1016199109.

  98. 98.

    Bicker F, Vasic V, Horta G, Ortega F, Nolte H, Kavyanifar A, et al. Neurovascular EGFL7 regulates adult neurogenesis in the subventricular zone and thereby affects olfactory perception. Nat Commun. 2017;8:15922. https://doi.org/10.1038/ncomms15922.

  99. 99.

    Sun J, Zhou W, Ma D, Yang Y. Endothelial cells promote neural stem cell proliferation and differentiation associated with VEGF activated Notch and Pten signaling. Dev Dyn. 2010;239(9):2345–53. https://doi.org/10.1002/dvdy.22377.

  100. 100.

    Jin K, Zhu Y, Sun Y, Mao XO, Xie L, Greenberg DA. Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo. Proc Natl Acad Sci U S A. 2002;99(18):11946–50. https://doi.org/10.1073/pnas.182296499.

  101. 101.

    Armulik A, Genove G, Betsholtz C. Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. Dev Cell. 2011;21(2):193–215. https://doi.org/10.1016/j.devcel.2011.07.001.

  102. 102.

    Aguirre A, Rubio ME, Gallo V. Notch and EGFR pathway interaction regulates neural stem cell number and self-renewal. Nature. 2010;467(7313):323–7. https://doi.org/10.1038/nature09347.

  103. 103.

    Liu X, Wang Q, Haydar TF, Bordey A. Nonsynaptic GABA signaling in postnatal subventricular zone controls proliferation of GFAP-expressing progenitors. Nat Neurosci. 2005;8(9):1179–87. https://doi.org/10.1038/nn1522.

  104. 104.

    Fernando RN, Eleuteri B, Abdelhady S, Nussenzweig A, Andang M, Ernfors P. Cell cycle restriction by histone H2AX limits proliferation of adult neural stem cells. Proc Natl Acad Sci U S A. 2011;108(14):5837–42. https://doi.org/10.1073/pnas.1014993108.

  105. 105.

    Lee N, Batt MK, Cronier BA, Jackson MC, Bruno Garza JL, Trinh DS, et al. Ciliary neurotrophic factor receptor regulation of adult forebrain neurogenesis. J Neurosci. 2013;33(3):1241–58. https://doi.org/10.1523/JNEUROSCI.3386-12.2013.

  106. 106.

    Gomez-Nicola D, Valle-Argos B, Pallas-Bazarra N, Nieto-Sampedro M. Interleukin-15 regulates proliferation and self-renewal of adult neural stem cells. Mol Biol Cell. 2011;22(12):1960–70. https://doi.org/10.1091/mbc.E11-01-0053.

  107. 107.

    Bozoyan L, Khlghatyan J, Saghatelyan A. Astrocytes control the development of the migration-promoting vasculature scaffold in the postnatal brain via VEGF signaling. J Neurosci. 2012;32(5):1687–704. https://doi.org/10.1523/JNEUROSCI.5531-11.2012.

  108. 108.

    Bolteus AJ, Bordey A. GABA release and uptake regulate neuronal precursor migration in the postnatal subventricular zone. J Neurosci. 2004;24(35):7623–31. https://doi.org/10.1523/JNEUROSCI.1999-04.2004.

  109. 109.

    Hurtado-Chong A, Yusta-Boyo MJ, Vergano-Vera E, Bulfone A, de Pablo F, Vicario-Abejon C. IGF-I promotes neuronal migration and positioning in the olfactory bulb and the exit of neuroblasts from the subventricular zone. Eur J Neurosci. 2009;30(5):742–55. https://doi.org/10.1111/j.1460-9568.2009.06870.x.

  110. 110.

    Marques F, Sousa JC, Coppola G, Gao F, Puga R, Brentani H, et al. Transcriptome signature of the adult mouse choroid plexus. Fluids Barriers CNS. 2011;8(1):10. https://doi.org/10.1186/2045-8118-8-10.

  111. 111.

    Liddelow SA, Temple S, Mollgard K, Gehwolf R, Wagner A, Bauer H, et al. Molecular characterisation of transport mechanisms at the developing mouse blood-CSF interface: a transcriptome approach. PLoS One. 2012;7(3):e33554. https://doi.org/10.1371/journal.pone.0033554.

  112. 112.

    Silva-Vargas V, Maldonado-Soto AR, Mizrak D, Codega P, Doetsch F. Age-dependent niche signals from the choroid plexus regulate adult neural stem cells. Cell Stem Cell. 2016;19(5):643–52. https://doi.org/10.1016/j.stem.2016.06.013.

  113. 113.

    Lehtinen MK, Zappaterra MW, Chen X, Yang YJ, Hill AD, Lun M, et al. The cerebrospinal fluid provides a proliferative niche for neural progenitor cells. Neuron. 2011;69(5):893–905. https://doi.org/10.1016/j.neuron.2011.01.023.

  114. 114.

    Faissner A, Reinhard J. The extracellular matrix compartment of neural stem and glial progenitor cells. Glia. 2015;63(8):1330–49. https://doi.org/10.1002/glia.22839.

  115. 115.

    Mercier F, Kitasako JT, Hatton GI. Anatomy of the brain neurogenic zones revisited: fractones and the fibroblast/macrophage network. J Comp Neurol. 2002;451(2):170–88. https://doi.org/10.1002/cne.10342.

  116. 116.

    Barros CS, Franco SJ, Muller U. Extracellular matrix: functions in the nervous system. Cold Spring Harb Perspect Biol. 2011;3(1):a005108. https://doi.org/10.1101/cshperspect.a005108.

  117. 117.

    Dityatev A, Schachner M, Sonderegger P. The dual role of the extracellular matrix in synaptic plasticity and homeostasis. Nat Rev Neurosci. 2010;11(11):735–46. https://doi.org/10.1038/nrn2898.

  118. 118.

    Fietz SA, Lachmann R, Brandl H, Kircher M, Samusik N, Schroder R, et al. Transcriptomes of germinal zones of human and mouse fetal neocortex suggest a role of extracellular matrix in progenitor self-renewal. Proc Natl Acad Sci U S A. 2012;109(29):11836–41. https://doi.org/10.1073/pnas.1209647109.

  119. 119.

    Kerever A, Mercier F, Nonaka R, de Vega S, Oda Y, Zalc B, et al. Perlecan is required for FGF-2 signaling in the neural stem cell niche. Stem Cell Res. 2014;12(2):492–505. https://doi.org/10.1016/j.scr.2013.12.009.

  120. 120.

    Bonfanti L, Peretto P. Adult neurogenesis in mammals--a theme with many variations. Eur J Neurosci. 2011;34(6):930–50. https://doi.org/10.1111/j.1460-9568.2011.07832.x.

  121. 121.

    Spalding KL, Bhardwaj RD, Buchholz BA, Druid H, Frisen J. Retrospective birth dating of cells in humans. Cell. 2005;122(1):133–43. https://doi.org/10.1016/j.cell.2005.04.028.

  122. 122.

    Bhardwaj RD, Curtis MA, Spalding KL, Buchholz BA, Fink D, Bjork-Eriksson T, et al. Neocortical neurogenesis in humans is restricted to development. Proc Natl Acad Sci U S A. 2006;103(33):12564–8. https://doi.org/10.1073/pnas.0605177103.

  123. 123.

    Bergmann O, Spalding KL, Frisen J. Adult neurogenesis in humans. Cold Spring Harb Perspect Biol. 2015;7(7):a018994. https://doi.org/10.1101/cshperspect.a018994.

  124. 124.

    Lepousez G, Nissant A, Lledo PM. Adult neurogenesis and the future of the rejuvenating brain circuits. Neuron. 2015;86(2):387–401. https://doi.org/10.1016/j.neuron.2015.01.002.

  125. 125.

    Deng W, Aimone JB, Gage FH. New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? Nat Rev Neurosci. 2010;11(5):339–50. https://doi.org/10.1038/nrn2822.

  126. 126.

    Boldrini M, Underwood MD, Hen R, Rosoklija GB, Dwork AJ, John Mann J, et al. Antidepressants increase neural progenitor cells in the human hippocampus. Neuropsychopharmacology. 2009;34(11):2376–89. https://doi.org/10.1038/npp.2009.75.

  127. 127.

    Kang E, Wen Z, Song H, Christian KM, Ming GL. Adult neurogenesis and psychiatric disorders. Cold Spring Harb Perspect Biol. 2016;8(9). https://doi.org/10.1101/cshperspect.a019026.

  128. 128.

    Lazarini F, Lledo PM. Is adult neurogenesis essential for olfaction? Trends Neurosci. 2011;34(1):20–30. https://doi.org/10.1016/j.tins.2010.09.006.

  129. 129.

    Bergmann O, Liebl J, Bernard S, Alkass K, Yeung MS, Steier P, et al. The age of olfactory bulb neurons in humans. Neuron. 2012;74(4):634–9. https://doi.org/10.1016/j.neuron.2012.03.030.

  130. 130.

    Sanai N, Nguyen T, Ihrie RA, Mirzadeh Z, Tsai HH, Wong M, et al. Corridors of migrating neurons in the human brain and their decline during infancy. Nature. 2011;478(7369):382–6. https://doi.org/10.1038/nature10487.

  131. 131.

    Wang C, Liu F, Liu YY, Zhao CH, You Y, Wang L, et al. Identification and characterization of neuroblasts in the subventricular zone and rostral migratory stream of the adult human brain. Cell Res. 2011;21(11):1534–50. https://doi.org/10.1038/cr.2011.83.

  132. 132.

    Dennis CV, Suh LS, Rodriguez ML, Kril JJ, Sutherland GT. Human adult neurogenesis across the ages: an immunohistochemical study. Neuropathol Appl Neurobiol. 2016;42(7):621–38. https://doi.org/10.1111/nan.12337.

  133. 133.

    Ernst A, Alkass K, Bernard S, Salehpour M, Perl S, Tisdale J, et al. Neurogenesis in the striatum of the adult human brain. Cell. 2014;156(5):1072–83. https://doi.org/10.1016/j.cell.2014.01.044.

  134. 134.

    Jin K, Wang X, Xie L, Mao XO, Zhu W, Wang Y, et al. Evidence for stroke-induced neurogenesis in the human brain. Proc Natl Acad Sci U S A. 2006;103(35):13198–202. https://doi.org/10.1073/pnas.0603512103.

  135. 135.

    Macas J, Nern C, Plate KH, Momma S. Increased generation of neuronal progenitors after ischemic injury in the aged adult human forebrain. J Neurosci. 2006;26(50):13114–9. https://doi.org/10.1523/JNEUROSCI.4667-06.2006.

  136. 136.

    Minger SL, Ekonomou A, Carta EM, Chinoy A, Perry RH, Ballard CG. Endogenous neurogenesis in the human brain following cerebral infarction. Regen Med. 2007;2(1):69–74. https://doi.org/10.2217/17460751.2.1.69.

  137. 137.

    Marti-Fabregas J, Romaguera-Ros M, Gomez-Pinedo U, Martinez-Ramirez S, Jimenez-Xarrie E, Marin R, et al. Proliferation in the human ipsilateral subventricular zone after ischemic stroke. Neurology. 2010;74(5):357–65. https://doi.org/10.1212/WNL.0b013e3181cbccec.

  138. 138.

    Nakayama D, Matsuyama T, Ishibashi-Ueda H, Nakagomi T, Kasahara Y, Hirose H, et al. Injury-induced neural stem/progenitor cells in post-stroke human cerebral cortex. Eur J Neurosci. 2010;31(1):90–8.

  139. 139.

    Wang X, Mao X, Xie L, Sun F, Greenberg DA, Jin K. Conditional depletion of neurogenesis inhibits long-term recovery after experimental stroke in mice. PLoS One. 2012;7(6):e38932. https://doi.org/10.1371/journal.pone.0038932.

  140. 140.

    Sun C, Sun H, Wu S, Lee CC, Akamatsu Y, Wang RK, et al. Conditional ablation of neuroprogenitor cells in adult mice impedes recovery of poststroke cognitive function and reduces synaptic connectivity in the perforant pathway. J Neurosci. 2013;33(44):17314–25. https://doi.org/10.1523/JNEUROSCI.2129-13.2013.

  141. 141.

    Lindvall O, Kokaia Z. Neurogenesis following stroke affecting the adult brain. Cold Spring Harb Perspect Biol. 2015;7(11). https://doi.org/10.1101/cshperspect.a019034.

  142. 142.

    Marlier Q, Verteneuil S, Vandenbosch R, Malgrange B. Mechanisms and functional significance of stroke-induced neurogenesis. Front Neurosci. 2015;9:458. https://doi.org/10.3389/fnins.2015.00458.

  143. 143.

    Ottoboni L, Merlini A, Martino G. Neural stem cell plasticity: advantages in therapy for the injured central nervous system. Front Cell Dev Biol. 2017;5:52. https://doi.org/10.3389/fcell.2017.00052.

  144. 144.

    Lu J, Manaenko A, Hu Q. Targeting adult neurogenesis for poststroke therapy. Stem Cells Int. 2017;2017:5868632. https://doi.org/10.1155/2017/5868632.

  145. 145.

    Tang H, Wang Y, Xie L, Mao X, Won SJ, Galvan V, et al. Effect of neural precursor proliferation level on neurogenesis in rat brain during aging and after focal ischemia. Neurobiol Aging. 2009;30(2):299–308. https://doi.org/10.1016/j.neurobiolaging.2007.06.004.

  146. 146.

    Zhang RL, Zhang ZG, Lu M, Wang Y, Yang JJ, Chopp M. Reduction of the cell cycle length by decreasing G1 phase and cell cycle reentry expand neuronal progenitor cells in the subventricular zone of adult rat after stroke. J Cereb Blood Flow Metab. 2006;26(6):857–63. https://doi.org/10.1038/sj.jcbfm.9600237.

  147. 147.

    Zhang R, Zhang Z, Wang L, Wang Y, Gousev A, Zhang L, et al. Activated neural stem cells contribute to stroke-induced neurogenesis and neuroblast migration toward the infarct boundary in adult rats. J Cereb Blood Flow Metab. 2004;24(4):441–8. https://doi.org/10.1097/00004647-200404000-00009.

  148. 148.

    Thored P, Arvidsson A, Cacci E, Ahlenius H, Kallur T, Darsalia V, et al. Persistent production of neurons from adult brain stem cells during recovery after stroke. Stem Cells. 2006;24(3):739–47. https://doi.org/10.1634/stemcells.2005-0281.

  149. 149.

    Sawada M, Matsumoto M, Sawamoto K. Vascular regulation of adult neurogenesis under physiological and pathological conditions. Front Neurosci. 2014;8:53. https://doi.org/10.3389/fnins.2014.00053.

  150. 150.

    Jin K, Sun Y, Xie L, Peel A, Mao XO, Batteur S, et al. Directed migration of neuronal precursors into the ischemic cerebral cortex and striatum. Mol Cell Neurosci. 2003;24(1):171–89.

  151. 151.

    Yamashita T, Ninomiya M, Hernandez Acosta P, Garcia-Verdugo JM, Sunabori T, Sakaguchi M, et al. Subventricular zone-derived neuroblasts migrate and differentiate into mature neurons in the post-stroke adult striatum. J Neurosci. 2006;26(24):6627–36. https://doi.org/10.1523/JNEUROSCI.0149-06.2006.

  152. 152.

    Ohab JJ, Fleming S, Blesch A, Carmichael ST. A neurovascular niche for neurogenesis after stroke. J Neurosci. 2006;26(50):13007–16. https://doi.org/10.1523/JNEUROSCI.4323-06.2006.

  153. 153.

    Thored P, Wood J, Arvidsson A, Cammenga J, Kokaia Z, Lindvall O. Long-term neuroblast migration along blood vessels in an area with transient angiogenesis and increased vascularization after stroke. Stroke. 2007;38(11):3032–9. https://doi.org/10.1161/STROKEAHA.107.488445.

  154. 154.

    Lee SR, Kim HY, Rogowska J, Zhao BQ, Bhide P, Parent JM, et al. Involvement of matrix metalloproteinase in neuroblast cell migration from the subventricular zone after stroke. J Neurosci. 2006;26(13):3491–5. https://doi.org/10.1523/JNEUROSCI.4085-05.2006.

  155. 155.

    Zarco N, Norton E, Quinones-Hinojosa A, Guerrero-Cazares H. Overlapping migratory mechanisms between neural progenitor cells and brain tumor stem cells. Cell Mol Life Sci. 2019. https://doi.org/10.1007/s00018-019-03149-7.

  156. 156.

    Fujioka T, Kaneko N, Sawamoto K. Blood vessels as a scaffold for neuronal migration. Neurochem Int. 2019;126:69–73. https://doi.org/10.1016/j.neuint.2019.03.001.

  157. 157.

    Zhang RL, Chopp M, Gregg SR, Toh Y, Roberts C, Letourneau Y, et al. Patterns and dynamics of subventricular zone neuroblast migration in the ischemic striatum of the adult mouse. J Cereb Blood Flow Metab. 2009;29(7):1240–50. https://doi.org/10.1038/jcbfm.2009.55.

  158. 158.

    Kojima T, Hirota Y, Ema M, Takahashi S, Miyoshi I, Okano H, et al. Subventricular zone-derived neural progenitor cells migrate along a blood vessel scaffold toward the post-stroke striatum. Stem Cells. 2010;28(3):545–54. https://doi.org/10.1002/stem.306.

  159. 159.

    Grade S, Weng YC, Snapyan M, Kriz J, Malva JO, Saghatelyan A. Brain-derived neurotrophic factor promotes vasculature-associated migration of neuronal precursors toward the ischemic striatum. PLoS One. 2013;8(1):e55039. https://doi.org/10.1371/journal.pone.0055039.

  160. 160.

    Arvidsson A, Collin T, Kirik D, Kokaia Z, Lindvall O. Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat Med. 2002;8(9):963–70. https://doi.org/10.1038/nm747.

  161. 161.

    Parent JM, Vexler ZS, Gong C, Derugin N, Ferriero DM. Rat forebrain neurogenesis and striatal neuron replacement after focal stroke. Ann Neurol. 2002;52(6):802–13. https://doi.org/10.1002/ana.10393.

  162. 162.

    Liu F, You Y, Li X, Ma T, Nie Y, Wei B, et al. Brain injury does not alter the intrinsic differentiation potential of adult neuroblasts. J Neurosci. 2009;29(16):5075–87. https://doi.org/10.1523/JNEUROSCI.0201-09.2009.

  163. 163.

    Hou SW, Wang YQ, Xu M, Shen DH, Wang JJ, Huang F, et al. Functional integration of newly generated neurons into striatum after cerebral ischemia in the adult rat brain. Stroke. 2008;39(10):2837–44. https://doi.org/10.1161/STROKEAHA.107.510982.

  164. 164.

    Sun X, Zhang QW, Xu M, Guo JJ, Shen SW, Wang YQ, et al. New striatal neurons form projections to substantia nigra in adult rat brain after stroke. Neurobiol Dis. 2012;45(1):601–9. https://doi.org/10.1016/j.nbd.2011.09.018.

  165. 165.

    Turnley AM, Basrai HS, Christie KJ. Is integration and survival of newborn neurons the bottleneck for effective neural repair by endogenous neural precursor cells? Front Neurosci. 2014;8:29. https://doi.org/10.3389/fnins.2014.00029.

  166. 166.

    Leker RR, Soldner F, Velasco I, Gavin DK, Androutsellis-Theotokis A, McKay RD. Long-lasting regeneration after ischemia in the cerebral cortex. Stroke. 2007;38(1):153–61. https://doi.org/10.1161/01.STR.0000252156.65953.a9.

  167. 167.

    Kreuzberg M, Kanov E, Timofeev O, Schwaninger M, Monyer H, Khodosevich K. Increased subventricular zone-derived cortical neurogenesis after ischemic lesion. Exp Neurol. 2010;226(1):90–9. https://doi.org/10.1016/j.expneurol.2010.08.006.

  168. 168.

    Christie KJ, Emery B, Denham M, Bujalka H, Cate HS, Turnley AM. Transcriptional regulation and specification of neural stem cells. Adv Exp Med Biol. 2013;786:129–55. https://doi.org/10.1007/978-94-007-6621-1_8.

  169. 169.

    Chancey JH, Adlaf EW, Sapp MC, Pugh PC, Wadiche JI, Overstreet-Wadiche LS. GABA depolarization is required for experience-dependent synapse unsilencing in adult-born neurons. J Neurosci. 2013;33(15):6614–22. https://doi.org/10.1523/JNEUROSCI.0781-13.2013.

  170. 170.

    Hoehn BD, Palmer TD, Steinberg GK. Neurogenesis in rats after focal cerebral ischemia is enhanced by indomethacin. Stroke. 2005;36(12):2718–24. https://doi.org/10.1161/01.STR.0000190020.30282.cc.

  171. 171.

    Thored P, Heldmann U, Gomes-Leal W, Gisler R, Darsalia V, Taneera J, et al. Long-term accumulation of microglia with proneurogenic phenotype concomitant with persistent neurogenesis in adult subventricular zone after stroke. Glia. 2009;57(8):835–49. https://doi.org/10.1002/glia.20810.

  172. 172.

    Frisen J. Neurogenesis and gliogenesis in nervous system plasticity and repair. Annu Rev Cell Dev Biol. 2016;32:127–41. https://doi.org/10.1146/annurev-cellbio-111315-124953.

  173. 173.

    Ruan L, Wang B, ZhuGe Q, Jin K. Coupling of neurogenesis and angiogenesis after ischemic stroke. Brain Res. 1623;2015:166–73. https://doi.org/10.1016/j.brainres.2015.02.042.

  174. 174.

    Cayre M, Courtes S, Martineau F, Giordano M, Arnaud K, Zamaron A, et al. Netrin 1 contributes to vascular remodeling in the subventricular zone and promotes progenitor emigration after demyelination. Development. 2013;140(15):3107–17. https://doi.org/10.1242/dev.092999.

  175. 175.

    Kim H, Wei Y, Lee JY, Wu Y, Zheng Y, Moskowitz MA, et al. Myeloperoxidase inhibition increases neurogenesis after ischemic stroke. J Pharmacol Exp Ther. 2016;359(2):262–72. https://doi.org/10.1124/jpet.116.235127.

  176. 176.

    Chen J, Zacharek A, Zhang C, Jiang H, Li Y, Roberts C, et al. Endothelial nitric oxide synthase regulates brain-derived neurotrophic factor expression and neurogenesis after stroke in mice. J Neurosci. 2005;25(9):2366–75. https://doi.org/10.1523/JNEUROSCI.5071-04.2005.

  177. 177.

    Cui X, Chen J, Zacharek A, Roberts C, Yang Y, Chopp M. Nitric oxide donor up-regulation of SDF1/CXCR4 and Ang1/Tie2 promotes neuroblast cell migration after stroke. J Neurosci Res. 2009;87(1):86–95. https://doi.org/10.1002/jnr.21836.

  178. 178.

    Liu XS, Chopp M, Zhang RL, Hozeska-Solgot A, Gregg SC, Buller B, et al. Angiopoietin 2 mediates the differentiation and migration of neural progenitor cells in the subventricular zone after stroke. J Biol Chem. 2009;284(34):22680–9. https://doi.org/10.1074/jbc.M109.006551.

  179. 179.

    Perez-Asensio FJ, Perpina U, Planas AM, Pozas E. Interleukin-10 regulates progenitor differentiation and modulates neurogenesis in adult brain. J Cell Sci. 2013;126(Pt 18):4208–19. https://doi.org/10.1242/jcs.127803.

  180. 180.

    Guadagno J, Swan P, Shaikh R, Cregan SP. Microglia-derived IL-1beta triggers p53-mediated cell cycle arrest and apoptosis in neural precursor cells. Cell Death Dis. 2015;6:e1779. https://doi.org/10.1038/cddis.2015.151.

  181. 181.

    Meng C, Zhang JC, Shi RL, Zhang SH, Yuan SY. Inhibition of interleukin-6 abolishes the promoting effects of pair housing on post-stroke neurogenesis. Neuroscience. 2015;307:160–70. https://doi.org/10.1016/j.neuroscience.2015.08.055.

  182. 182.

    Osman AM, Neumann S, Kuhn HG, Blomgren K. Caspase inhibition impaired the neural stem/progenitor cell response after cortical ischemia in mice. Oncotarget. 2016;7(3):2239–48. https://doi.org/10.18632/oncotarget.6803.

  183. 183.

    Felfly H, Zambon AC, Xue J, Muotri A, Zhou D, Snyder EY, et al. Severe hypoxia: consequences to neural stem cells and neurons. J Neurol Res. 2011;1(5). https://doi.org/10.4021/jnr70w.

  184. 184.

    Santilli G, Lamorte G, Carlessi L, Ferrari D, Rota Nodari L, Binda E, et al. Mild hypoxia enhances proliferation and multipotency of human neural stem cells. PLoS One. 2010;5(1):e8575. https://doi.org/10.1371/journal.pone.0008575.

  185. 185.

    Guerra-Crespo M, Gleason D, Sistos A, Toosky T, Solaroglu I, Zhang JH, et al. Transforming growth factor-alpha induces neurogenesis and behavioral improvement in a chronic stroke model. Neuroscience. 2009;160(2):470–83. https://doi.org/10.1016/j.neuroscience.2009.02.029.

  186. 186.

    Benner EJ, Luciano D, Jo R, Abdi K, Paez-Gonzalez P, Sheng H, et al. Protective astrogenesis from the SVZ niche after injury is controlled by Notch modulator Thbs4. Nature. 2013;497(7449):369–73. https://doi.org/10.1038/nature12069.

  187. 187.

    Widera D, Mikenberg I, Elvers M, Kaltschmidt C, Kaltschmidt B. Tumor necrosis factor alpha triggers proliferation of adult neural stem cells via IKK/NF-kappaB signaling. BMC Neurosci. 2006;7:64. https://doi.org/10.1186/1471-2202-7-64.

  188. 188.

    Guadagno J, Xu X, Karajgikar M, Brown A, Cregan SP. Microglia-derived TNFalpha induces apoptosis in neural precursor cells via transcriptional activation of the Bcl-2 family member Puma. Cell Death Dis. 2013;4:e538. https://doi.org/10.1038/cddis.2013.59.

  189. 189.

    Li ST, Pan J, Hua XM, Liu H, Shen S, Liu JF, et al. Endothelial nitric oxide synthase protects neurons against ischemic injury through regulation of brain-derived neurotrophic factor expression. CNS Neurosci Ther. 2014;20(2):154–64. https://doi.org/10.1111/cns.12182.

  190. 190.

    Barkho BZ, Munoz AE, Li X, Li L, Cunningham LA, Zhao X. Endogenous matrix metalloproteinase (MMP)-3 and MMP-9 promote the differentiation and migration of adult neural progenitor cells in response to chemokines. Stem Cells. 2008;26(12):3139–49. https://doi.org/10.1634/stemcells.2008-0519.

  191. 191.

    Wang L, Zhang ZG, Zhang RL, Gregg SR, Hozeska-Solgot A, LeTourneau Y, et al. Matrix metalloproteinase 2 (MMP2) and MMP9 secreted by erythropoietin-activated endothelial cells promote neural progenitor cell migration. J Neurosci. 2006;26(22):5996–6003. https://doi.org/10.1523/JNEUROSCI.5380-05.2006.

  192. 192.

    Yan YP, Lang BT, Vemuganti R, Dempsey RJ. Osteopontin is a mediator of the lateral migration of neuroblasts from the subventricular zone after focal cerebral ischemia. Neurochem Int. 2009;55(8):826–32. https://doi.org/10.1016/j.neuint.2009.08.007.

  193. 193.

    Tsai PT, Ohab JJ, Kertesz N, Groszer M, Matter C, Gao J, et al. A critical role of erythropoietin receptor in neurogenesis and post-stroke recovery. J Neurosci. 2006;26(4):1269–74. https://doi.org/10.1523/JNEUROSCI.4480-05.2006.

  194. 194.

    Courtes S, Vernerey J, Pujadas L, Magalon K, Cremer H, Soriano E, et al. Reelin controls progenitor cell migration in the healthy and pathological adult mouse brain. PLoS One. 2011;6(5):e20430. https://doi.org/10.1371/journal.pone.0020430.

  195. 195.

    Kang SS, Keasey MP, Arnold SA, Reid R, Geralds J, Hagg T. Endogenous CNTF mediates stroke-induced adult CNS neurogenesis in mice. Neurobiol Dis. 2013;49:68–78. https://doi.org/10.1016/j.nbd.2012.08.020.

  196. 196.

    Zhang C, Wu H, Zhu X, Wang Y, Guo J. Role of transcription factors in neurogenesis after cerebral ischemia. Rev Neurosci. 2011;22(4):457–65. https://doi.org/10.1515/RNS.2011.034.

  197. 197.

    Koh SH, Park HH. Neurogenesis in stroke recovery. Transl Stroke Res. 2017;8(1):3–13. https://doi.org/10.1007/s12975-016-0460-z.

  198. 198.

    Wu KJ, Yu S, Lee JY, Hoffer B, Wang Y. Improving neurorepair in stroke brain through endogenous neurogenesis-enhancing drugs. Cell Transplant. 2017;26(9):1596–600. https://doi.org/10.1177/0963689717721230.

  199. 199.

    Pin-Barre C, Laurin J. Physical exercise as a diagnostic, rehabilitation, and preventive tool: influence on neuroplasticity and motor recovery after stroke. Neural Plast. 2015;2015:608581. https://doi.org/10.1155/2015/608581.

  200. 200.

    Enzinger C, Dawes H, Johansen-Berg H, Wade D, Bogdanovic M, Collett J, et al. Brain activity changes associated with treadmill training after stroke. Stroke. 2009;40(7):2460–7. https://doi.org/10.1161/STROKEAHA.109.550053.

  201. 201.

    Luft AR, Macko RF, Forrester LW, Villagra F, Ivey F, Sorkin JD, et al. Treadmill exercise activates subcortical neural networks and improves walking after stroke: a randomized controlled trial. Stroke. 2008;39(12):3341–50. https://doi.org/10.1161/STROKEAHA.108.527531.

  202. 202.

    Ploughman M, Austin MW, Glynn L, Corbett D. The effects of poststroke aerobic exercise on neuroplasticity: a systematic review of animal and clinical studies. Transl Stroke Res. 2015;6(1):13–28. https://doi.org/10.1007/s12975-014-0357-7.

  203. 203.

    Zheng HQ, Zhang LY, Luo J, Li LL, Li M, Zhang Q, et al. Physical exercise promotes recovery of neurological function after ischemic stroke in rats. Int J Mol Sci. 2014;15(6):10974–88. https://doi.org/10.3390/ijms150610974.

  204. 204.

    Zhang QW, Deng XX, Sun X, Xu JX, Sun FY. Exercise promotes axon regeneration of newborn striatonigral and corticonigral projection neurons in rats after ischemic stroke. PLoS One. 2013;8(11):e80139. https://doi.org/10.1371/journal.pone.0080139.

  205. 205.

    Coleman ER, Moudgal R, Lang K, Hyacinth HI, Awosika OO, Kissela BM, et al. Early rehabilitation after stroke: a narrative review. Curr Atheroscler Rep. 2017;19(12):59. https://doi.org/10.1007/s11883-017-0686-6.

  206. 206.

    Schmidt A, Wellmann J, Schilling M, Strecker JK, Sommer C, Schabitz WR, et al. Meta-analysis of the efficacy of different training strategies in animal models of ischemic stroke. Stroke. 2014;45(1):239–47. https://doi.org/10.1161/STROKEAHA.113.002048.

  207. 207.

    Risedal A, Zeng J, Johansson BB. Early training may exacerbate brain damage after focal brain ischemia in the rat. J Cereb Blood Flow Metab. 1999;19(9):997–1003. https://doi.org/10.1097/00004647-199909000-00007.

  208. 208.

    So JH, Huang C, Ge M, Cai G, Zhang L, Lu Y, et al. Intense exercise promotes adult hippocampal neurogenesis but not spatial discrimination. Front Cell Neurosci. 2017;11:13. https://doi.org/10.3389/fncel.2017.00013.

  209. 209.

    Dabrowski A, Robinson TJ, Felling RJ. Promoting brain repair and regeneration after stroke: a Plea for cell-based therapies. Curr Neurol Neurosci Rep. 2019;19(1):5. https://doi.org/10.1007/s11910-019-0920-4.

  210. 210.

    Janowski M, Wagner DC, Boltze J. Stem cell-based tissue replacement after stroke: factual necessity or notorious fiction? Stroke. 2015;46(8):2354–63. https://doi.org/10.1161/STROKEAHA.114.007803.

  211. 211.

    Dihne M, Hartung HP, Seitz RJ. Restoring neuronal function after stroke by cell replacement: anatomic and functional considerations. Stroke. 2011;42(8):2342–50. https://doi.org/10.1161/STROKEAHA.111.613422.

  212. 212.

    Gervois P, Wolfs E, Ratajczak J, Dillen Y, Vangansewinkel T, Hilkens P, et al. Stem cell-based therapies for ischemic stroke: preclinical results and the potential of imaging-assisted evaluation of donor cell fate and mechanisms of brain regeneration. Med Res Rev. 2016;36(6):1080–126. https://doi.org/10.1002/med.21400.

  213. 213.

    Carletti B, Piemonte F, Rossi F. Neuroprotection: the emerging concept of restorative neural stem cell biology for the treatment of neurodegenerative diseases. Curr Neuropharmacol. 2011;9(2):313–7. https://doi.org/10.2174/157015911795596603.

  214. 214.

    Madhavan L, Ourednik V, Ourednik J. Neural stem/progenitor cells initiate the formation of cellular networks that provide neuroprotection by growth factor-modulated antioxidant expression. Stem Cells. 2008;26(1):254–65. https://doi.org/10.1634/stemcells.2007-0221.

  215. 215.

    De Feo D, Merlini A, Laterza C, Martino G. Neural stem cell transplantation in central nervous system disorders: from cell replacement to neuroprotection. Curr Opin Neurol. 2012;25(3):322–33. https://doi.org/10.1097/WCO.0b013e328352ec45.

  216. 216.

    Zhao LR, Duan WM, Reyes M, Keene CD, Verfaillie CM, Low WC. Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats. Exp Neurol. 2002;174(1):11–20. https://doi.org/10.1006/exnr.2001.7853.

  217. 217.

    Liao W, Xie J, Zhong J, Liu Y, Du L, Zhou B, et al. Therapeutic effect of human umbilical cord multipotent mesenchymal stromal cells in a rat model of stroke. Transplantation. 2009;87(3):350–9. https://doi.org/10.1097/TP.0b013e318195742e.

  218. 218.

    Ding DC, Shyu WC, Chiang MF, Lin SZ, Chang YC, Wang HJ, et al. Enhancement of neuroplasticity through upregulation of beta1-integrin in human umbilical cord-derived stromal cell implanted stroke model. Neurobiol Dis. 2007;27(3):339–53. https://doi.org/10.1016/j.nbd.2007.06.010.

  219. 219.

    Shiota Y, Nagai A, Sheikh AM, Mitaki S, Mishima S, Yano S, et al. Transplantation of a bone marrow mesenchymal stem cell line increases neuronal progenitor cell migration in a cerebral ischemia animal model. Sci Rep. 2018;8(1):14951. https://doi.org/10.1038/s41598-018-33030-9.

  220. 220.

    Shen LH, Li Y, Chen J, Zhang J, Vanguri P, Borneman J, et al. Intracarotid transplantation of bone marrow stromal cells increases axon-myelin remodeling after stroke. Neuroscience. 2006;137(2):393–9. https://doi.org/10.1016/j.neuroscience.2005.08.092.

  221. 221.

    Lee JY, Xu K, Nguyen H, Guedes VA, Borlongan CV, Acosta SA. Stem cell-induced biobridges as possible tools to aid neuroreconstruction after CNS injury. Front Cell Dev Biol. 2017;5:51. https://doi.org/10.3389/fcell.2017.00051.

  222. 222.

    Liska MG, Crowley MG, Nguyen H, Borlongan CV. Biobridge concept in stem cell therapy for ischemic stroke. J Neurosurg Sci. 2017;61(2):173–9. https://doi.org/10.23736/S0390-5616.16.03791-7.

  223. 223.

    Liska MG, Crowley MG, Borlongan CV. Regulated and unregulated clinical trials of stem cell therapies for stroke. Transl Stroke Res. 2017;8(2):93–103. https://doi.org/10.1007/s12975-017-0522-x.

  224. 224.

    Muir KW. Clinical trial design for stem cell therapies in stroke: what have we learned? Neurochem Int. 2017;106:108–13. https://doi.org/10.1016/j.neuint.2016.09.011.

  225. 225.

    Savitz SI, Cramer SC, Wechsler L, Consortium S. Stem cells as an emerging paradigm in stroke 3: enhancing the development of clinical trials. Stroke. 2014;45(2):634–9. https://doi.org/10.1161/STROKEAHA.113.003379.

  226. 226.

    Klomjai W, Lackmy-Vallee A, Roche N, Pradat-Diehl P, Marchand-Pauvert V, Katz R. Repetitive transcranial magnetic stimulation and transcranial direct current stimulation in motor rehabilitation after stroke: an update. Ann Phys Rehabil Med. 2015;58(4):220–4. https://doi.org/10.1016/j.rehab.2015.05.006.

  227. 227.

    Segal Y, Segal L, Blumenfeld-Katzir T, Sasson E, Poliansky V, Loeb E, et al. The effect of electromagnetic field treatment on recovery from ischemic stroke in a rat stroke model: clinical, imaging, and pathological findings. Stroke Res Treat. 2016;2016:6941946. https://doi.org/10.1155/2016/6941946.

  228. 228.

    Machado S, Bittencourt J, Minc D, Portella CE, Velasques B, Cunha M, et al. Therapeutic applications of repetitive transcranial magnetic stimulation in clinical neurorehabilitation. Funct Neurol. 2008;23(3):113–22.

  229. 229.

    Kubis N. Non-invasive brain stimulation to enhance post-stroke recovery. Front Neural Circuits. 2016;10:56. https://doi.org/10.3389/fncir.2016.00056.

  230. 230.

    Faralli A, Bigoni M, Mauro A, Rossi F, Carulli D. Noninvasive strategies to promote functional recovery after stroke. Neural Plast. 2013;2013:854597. https://doi.org/10.1155/2013/854597.

  231. 231.

    Hummel F, Celnik P, Giraux P, Floel A, Wu WH, Gerloff C, et al. Effects of non-invasive cortical stimulation on skilled motor function in chronic stroke. Brain. 2005;128(Pt 3):490–9. https://doi.org/10.1093/brain/awh369.

  232. 232.

    Sparing R, Thimm M, Hesse MD, Kust J, Karbe H, Fink GR. Bidirectional alterations of interhemispheric parietal balance by non-invasive cortical stimulation. Brain. 2009;132(Pt 11):3011–20. https://doi.org/10.1093/brain/awp154.

  233. 233.

    Takeuchi N, Chuma T, Matsuo Y, Watanabe I, Ikoma K. Repetitive transcranial magnetic stimulation of contralesional primary motor cortex improves hand function after stroke. Stroke. 2005;36(12):2681–6. https://doi.org/10.1161/01.STR.0000189658.51972.34.

  234. 234.

    Liepert J, Zittel S, Weiller C. Improvement of dexterity by single session low-frequency repetitive transcranial magnetic stimulation over the contralesional motor cortex in acute stroke: a double-blind placebo-controlled crossover trial. Restor Neurol Neurosci. 2007;25(5–6):461–5.

  235. 235.

    Rueger MA, Keuters MH, Walberer M, Braun R, Klein R, Sparing R, et al. Multi-session transcranial direct current stimulation (tDCS) elicits inflammatory and regenerative processes in the rat brain. PLoS One. 2012;7(8):e43776. https://doi.org/10.1371/journal.pone.0043776.

  236. 236.

    Keuters MH, Aswendt M, Tennstaedt A, Wiedermann D, Pikhovych A, Rotthues S, et al. Transcranial direct current stimulation promotes the mobility of engrafted NSCs in the rat brain. NMR Biomed. 2015;28(2):231–9. https://doi.org/10.1002/nbm.3244.

  237. 237.

    Pikhovych A, Stolberg NP, Jessica Flitsch L, Walter HL, Graf R, Fink GR, et al. Transcranial direct current stimulation modulates neurogenesis and microglia activation in the mouse brain. Stem Cells Int. 2016;2016:2715196. https://doi.org/10.1155/2016/2715196.

  238. 238.

    Braun R, Klein R, Walter HL, Ohren M, Freudenmacher L, Getachew K, et al. Transcranial direct current stimulation accelerates recovery of function, induces neurogenesis and recruits oligodendrocyte precursors in a rat model of stroke. Exp Neurol. 2016;279:127–36. https://doi.org/10.1016/j.expneurol.2016.02.018.

  239. 239.

    Yoon KJ, Oh BM, Kim DY. Functional improvement and neuroplastic effects of anodal transcranial direct current stimulation (tDCS) delivered 1 day vs. 1 week after cerebral ischemia in rats. Brain Res. 2012;1452:61–72. https://doi.org/10.1016/j.brainres.2012.02.062.

  240. 240.

    Guo F, Lou J, Han X, Deng Y, Huang X. Repetitive transcranial magnetic stimulation ameliorates cognitive impairment by enhancing neurogenesis and suppressing apoptosis in the Hippocampus in rats with ischemic stroke. Front Physiol. 2017;8:559. https://doi.org/10.3389/fphys.2017.00559.

  241. 241.

    Guo F, Han X, Zhang J, Zhao X, Lou J, Chen H, et al. Repetitive transcranial magnetic stimulation promotes neural stem cell proliferation via the regulation of MiR-25 in a rat model of focal cerebral ischemia. PLoS One. 2014;9(10):e109267. https://doi.org/10.1371/journal.pone.0109267.

  242. 242.

    Luo J, Zheng H, Zhang L, Zhang Q, Li L, Pei Z, et al. High-frequency repetitive transcranial magnetic stimulation (rTMS) improves functional recovery by enhancing neurogenesis and activating BDNF/TrkB signaling in ischemic rats. Int J Mol Sci. 2017;18(2):455. https://doi.org/10.3390/ijms18020455.

  243. 243.

    Cichon N, Bijak M, Czarny P, Miller E, Synowiec E, Sliwinski T, et al. Increase in blood levels of growth factors involved in the neuroplasticity process by using an extremely low frequency electromagnetic field in post-stroke patients. Front Aging Neurosci. 2018;10:294. https://doi.org/10.3389/fnagi.2018.00294.

  244. 244.

    Piacentini R, Ripoli C, Mezzogori D, Azzena GB, Grassi C. Extremely low-frequency electromagnetic fields promote in vitro neurogenesis via upregulation of Ca(v)1-channel activity. J Cell Physiol. 2008;215(1):129–39. https://doi.org/10.1002/jcp.21293.

  245. 245.

    Cheng Y, Dai Y, Zhu X, Xu H, Cai P, Xia R, et al. Extremely low-frequency electromagnetic fields enhance the proliferation and differentiation of neural progenitor cells cultured from ischemic brains. Neuroreport. 2015;26(15):896–902. https://doi.org/10.1097/WNR.0000000000000450.

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Correspondence to Annelies Bronckaers.

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Dillen, Y., Kemps, H., Gervois, P. et al. Adult Neurogenesis in the Subventricular Zone and Its Regulation After Ischemic Stroke: Implications for Therapeutic Approaches. Transl. Stroke Res. 11, 60–79 (2020) doi:10.1007/s12975-019-00717-8

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Keywords

  • Adult neurogenesis
  • Subventricular zone
  • Ischemic stroke
  • Neural stem cells
  • Stroke therapy