There is growing evidence for a tentative cellular repair in the forebrain following perinatal injuries. In this review, we present the evidences and shortcomings in this regenerative attempt. We discuss recent progress in elucidating the origin, diversity, and competence of postnatal neural stem cells/progenitor cells. Finally, we propose new strategies to recruit postnatal progenitors to generate specific subtypes of cortical neurons or oligodendrocytes, thereby allowing the development of tailor-made approaches to treat perinatal brain injuries.
AlsioJMTarchiniBCayouetteMLiveseyFJ. 2013. Ikaros promotes early-born neuronal fates in the cerebral cortex. Proc Natl Acad Sci U S A110(8):E716–25.
2.
AndersonMABurdaJERenYAoYO’SheaTMKawaguchiR, and others. 2016. Astrocyte scar formation aids central nervous system axon regeneration. Nature532(7598):195–200.
3.
AzimKBerningerBRaineteauO.2016. Mosaic subventricular origins of forebrain oligodendrogenesis. Front Neurosci10:107.
4.
AzimKFischerBHurtado-ChongADraganovaKCantuCZemkeM, and others. 2014a. Persistent Wnt/beta-catenin signaling determines dorsalization of the postnatal subventricular zone and neural stem cell specification into oligodendrocytes and glutamatergic neurons. Stem Cells32(5):1301–12.
5.
AzimKRiveraARaineteauOButtAM. 2014b. GSK3β regulates oligodendrogenesis in the dorsal microdomain of the subventricular zone via Wnt-beta-catenin signaling. Glia62(5):778–9.
6.
BackSATuohyTMChenHWallingfordNCraigAStruveJ, and others. 2005. Hyaluronan accumulates in demyelinated lesions and inhibits oligodendrocyte progenitor maturation. Nat Med11(9):966–72.
7.
BiBSalmasoNKomitovaMSimoniniMVSilbereisJChengE, and others. 2011. Cortical glial fibrillary acidic protein-positive cells generate neurons after perinatal hypoxic injury. J Neurosci31(25):9205–21.
8.
BrillMSNinkovicJWinpennyEHodgeRDOzenIYangR, and others. 2009. Adult generation of glutamatergic olfactory bulb interneurons. Nat Neurosci12(12):1524–33.
9.
BuffoARiteITripathiPLepierAColakDHornAP, and others. 2008. Origin and progeny of reactive gliosis: a source of multipotent cells in the injured brain. Proc Natl Acad Sci U S A105(9):3581–6.
10.
CalzolariFMichelJBaumgartEVTheisFGotzMNinkovicJ.2015. Fast clonal expansion and limited neural stem cell self-renewal in the adult subependymal zone. Nat Neurosci18(4):490–2.
11.
CarlenMMeletisKGoritzCDarsaliaVEvergrenETanigakiK, and others. 2009. Forebrain ependymal cells are Notch-dependent and generate neuroblasts and astrocytes after stroke. Nat Neurosci12(3):259–67.
12.
CavinessVSJrGotoTTaruiTTakahashiTBhidePGNowakowskiRS. 2003. Cell output, cell cycle duration and neuronal specification: a model of integrated mechanisms of the neocortical proliferative process. Cereb Cortex13(6):592–8.
13.
ChenHLPistollatoFHoeppnerDJNiHTMcKayRDPanchisionDM. 2007. Oxygen tension regulates survival and fate of mouse central nervous system precursors at multiple levels. Stem Cells25(9):2291–301.
14.
CodegaPSilva-VargasVPaulAMaldonado-SotoARDeleoAMPastranaE, and others. 2014. Prospective identification and purification of quiescent adult neural stem cells from their in vivo niche. Neuron82(3):545–59.
15.
CoveyMVJiangYAlliVVYangZLevisonSW. 2010. Defining the critical period for neocortical neurogenesis after pediatric brain injury. Dev Neurosci32(5-6):488–98.
16.
DaynacMTirouLFaureHMouthonMAGauthierLRHahnH, and others. 2016. Hedgehog controls quiescence and activation of neural stem cells in the adult ventricular-subventricular zone. Stem Cell Reports7(4):735–48.
17.
de HaanMWyattJSRothSVargha-KhademFGadianDMishkinM.2006. Brain and cognitive- behavioural development after asphyxia at term birth. Dev Sci9(4):350–8.
18.
De la RossaABelloneCGoldingBVitaliIMossJToniN, and others. 2013. In vivo reprogramming of circuit connectivity in postmitotic neocortical neurons. Nat Neurosci16(2):193–200.
19.
DesaiARMcConnellSK. 2000. Progressive restriction in fate potential by neural progenitors during cerebral cortical development. Development127(13):2863–72.
20.
Diaz-AlonsoJAguadoTWuCSPalazuelosJHofmannCGarcezP, and others. 2012. The CB(1) cannabinoid receptor drives corticospinal motor neuron differentiation through the Ctip2/Satb2 transcriptional regulation axis. J Neurosci32(47):16651–65.
21.
DonegaVNijboerCHvan TilborgGDijkhuizenRMKavelaarsAHeijnenCJ. 2014. Intranasally administered mesenchymal stem cells promote a regenerative niche for repair of neonatal ischemic brain injury. Exp Neurol261:53–64.
22.
FagelDMGanatYChengESilbereisJOhkuboYMentLR, and others. 2009. Fgfr1 is required for cortical regeneration and repair after perinatal hypoxia. J Neurosci29(4):1202–11.
23.
FagelDMGanatYSilbereisJEbbittTStewartWZhangH, and others. 2006. Cortical neurogenesis enhanced by chronic perinatal hypoxia. Exp Neurol199(1):77–91.
24.
FiorelliRAzimKFischerBRaineteauO.2015. Adding a spatial dimension to postnatal ventricular-subventricular zone neurogenesis. Development142(12):2109–20.
25.
FrantzGDMcConnellSK. 1996. Restriction of late cerebral cortical progenitors to an upper-layer fate. Neuron17(1):55–61.
26.
FuentealbaLCRompaniSBParraguezJIObernierKRomeroRCepkoCL, and others. 2015. Embryonic origin of postnatal neural stem cells. Cell161(7):1644–55.
27.
FukumitsuHOhtsukaMMuraiRNakamuraHItohKFurukawaS.2006. Brain-derived neurotrophic factor participates in determination of neuronal laminar fate in the developing mouse cerebral cortex. J Neurosci26(51):13218–30.
28.
FurutachiSMatsumotoANakayamaKIGotohY.2013. p57 controls adult neural stem cell quiescence and modulates the pace of lifelong neurogenesis. EMBO J32(7):970–81.
29.
FurutachiSMiyaHWatanabeTKawaiHYamasakiNHaradaY, and others. 2015. Slowly dividing neural progenitors are an embryonic origin of adult neural stem cells. Nat Neurosci18(5):657–65.
30.
GiachinoCBasakOLugertSKnucklesPObernierKFiorelliR, and others. 2014. Molecular diversity subdivides the adult forebrain neural stem cell population. Stem Cells32(1):70–84.
31.
GiulianDWoodwardJYoungDGKrebsJFLachmanLB. 1988. Interleukin-1 injected into mammalian brain stimulates astrogliosis and neovascularization. J Neurosci8(7):2485–90.
32.
GotzMSirkoSBeckersJIrmlerM.2015. Reactive astrocytes as neural stem or progenitor cells: in vivo lineage, in vitro potential, and genome-wide expression analysis. Glia63(8):1452–68.
33.
HagbergHGressensPMallardC.2012. Inflammation during fetal and neonatal life: implications for neurologic and neuropsychiatric disease in children and adults. Ann Neurol71(4):444–57.
34.
IhrieRAShahJKHarwellCCLevineJHGuintoCDLezametaM, and others. 2011. Persistent sonic hedgehog signaling in adult brain determines neural stem cell positional identity. Neuron71(2):250–62.
35.
ImayoshiISakamotoMYamaguchiMMoriKKageyamaR.2010. Essential roles of Notch signaling in maintenance of neural stem cells in developing and adult brains. J Neurosci30(9):3489–98.
36.
KennardMA.1936. Age and other factors in motor recovery for precentral lesions in monkeys. Am J Physiol. 115:138–46.
37.
KohwiMDoeCQ. 2013. Temporal fate specification and neural progenitor competence during development. Nat Rev Neurosci14(12):823–38.
38.
LagordCBerryMLoganA.2002. Expression of TGFbeta2 but not TGFbeta1 correlates with the deposition of scar tissue in the lesioned spinal cord. Mol Cell Neurosci20(1):69–92.
39.
LimDAFishellGJAlvarez-BuyllaA.1997. Postnatal mouse subventricular zone neuronal precursors can migrate and differentiate within multiple levels of the developing neuraxis. Proc Natl Acad Sci U S A94(26):14832–6.
40.
Llorens-BobadillaEZhaoSBaserASaiz-CastroGZwadloKMartin-VillalbaA.2015. Single-cell transcriptomics reveals a population of dormant neural stem cells that become activated upon brain injury. Cell Stem Cell17(3):329–40.
41.
MathieuJZhouWXingYSperberHFerreccioAAgostonZ and others. 2014. Hypoxia-inducible factors have distinct and stage-specific roles during reprogramming of human cells to pluripotency. Cell Stem Cell14(5):592–605.
42.
MazumdarJO’BrienWTJohnsonRSLaMannaJCChavezJCKleinPS, and others. 2010. O2 regulates stem cells through Wnt/beta-catenin signalling. Nat Cell Biol12(10):1007–13.
43.
McConnellSKKaznowskiCE. 1991. Cell cycle dependence of laminar determination in developing neocortex. Science254(5029):282–5.
44.
McKeonRJSchreiberRCRudgeJSSilverJ.1991. Reduction of neurite outgrowth in a model of glial scarring following CNS injury is correlated with the expression of inhibitory molecules on reactive astrocytes. J Neurosci11(11):3398–411.
45.
MendelsonAFrenettePS. 2014. Hematopoietic stem cell niche maintenance during homeostasis and regeneration. Nat Med20(8):833–46.
MerkleFTMirzadehZAlvarez-BuyllaA.2007. Mosaic organization of neural stem cells in the adult brain. Science317(5836):381–4.
48.
MyerDJGurkoffGGLeeSMHovdaDASofroniewMV. 2006. Essential protective roles of reactive astrocytes in traumatic brain injury. Brain129(10):2761–72.
49.
NobutaHGhianiCAPaezPMSpreuerVDongHKorsakRA, and others. 2012. STAT3-mediated astrogliosis protects myelin development in neonatal brain injury. Ann Neurol72(5):750–65.
50.
OhiraKFurutaTHiokiHNakamuraKCKuramotoETanakaY, and others. 2010. Ischemia-induced neurogenesis of neocortical layer 1 progenitor cells. Nat Neurosci13(2):173–9.
51.
OrtegaJASiroisCLMemiFGliddenNZecevicN.2016. Oxygen levels regulate the development of human cortical radial glia cells. Cereb Cortex. Epub Sep6. doi:10.1093/cercor/bhw194.
52.
PaikJHDingZNarurkarRRamkissoonSMullerFKamounWS, and others. 2009. FoxOs cooperatively regulate diverse pathways governing neural stem cell homeostasis. Cell Stem Cell5(5):540–53.
53.
ParedesMFJamesDGil-PerotinSKimHCotterJANgC, and others. 2016. Extensive migration of young neurons into the infant human frontal lobe. Science354(6308). doi:10.1126/science.aaf7073.
54.
PietrasEMReynaudDKangYACarlinDCalero-NietoFJLeavittAD, and others. 2015. Functionally distinct subsets of lineage-biased multipotent progenitors control blood production in normal and regenerative conditions. Cell Stem Cell17(1):35–46.
55.
QianXShenQGoderieSKHeWCapelaADavisAA, and others. 2000. Timing of CNS cell generation: a programmed sequence of neuron and glial cell production from isolated murine cortical stem cells. Neuron28(1):69–80.
RiccioOMurthySSzaboGVutskitsLKissJZVitalisT, and others. 2012. New pool of cortical interneuron precursors in the early postnatal dorsal white matter. Cereb Cortex22(1):86–98.
58.
RobelSBerningerBGotzM.2011. The stem cell potential of glia: lessons from reactive gliosis. Nat Rev Neurosci12(2):88–104.
59.
RodgersJTKingKYBrettJOCromieMJCharvilleGWMaguireKK, and others. 2014. mTORC1 controls the adaptive transition of quiescent stem cells from G0 to G(Alert). Nature510(7505):393–6.
60.
RouauxCArlottaP.2013. Direct lineage reprogramming of post-mitotic callosal neurons into corticofugal neurons in vivo. Nat Cell Biol15(2):214–21.
61.
SalmasoNJablonskaBScafidiJVaccarinoFMGalloV.2014. Neurobiology of premature brain injury. Nat Neurosci17(3):341–6.
62.
SanaiNPolleyMYMcDermottMWParsaATBergerMS. 2011. An extent of resection threshold for newly diagnosed glioblastomas. J Neurosurg115(1):3–8.
SequerraEBMiyakoshiLMFroesMMMenezesJRHedin-PereiraC.2010. Generation of glutamatergic neurons from postnatal and adult subventricular zone with pyramidal-like morphology. Cereb Cortex20(11):2583–91.
65.
ShenQWangYDimosJTFasanoCAPhoenixTNLemischkaIR, and others. 2006. The timing of cortical neurogenesis is encoded within lineages of individual progenitor cells. Nat Neurosci9(6):743–51.
66.
SilverJMillerJH. 2004. Regeneration beyond the glial scar. Nat Rev Neurosci5(2):146–56.
67.
SirkoSBehrendtGJohanssonPATripathiPCostaMBekS, and others. 2013. Reactive glia in the injured brain acquire stem cell properties in response to sonic hedgehog. Cell Stem Cell12(4):426–39.
68.
SirkoSNeitzAMittmannTHorvat-BrockerAvon HolstAEyselUT, and others. 2009. Focal laser-lesions activate an endogenous population of neural stem/progenitor cells in the adult visual cortex. Brain132:2252–64.
69.
SofroniewMV.2014. Multiple roles for astrocytes as effectors of cytokines and inflammatory mediators. Neuroscientist20(2):160–72.
70.
SpasskyNMerkleFTFlamesNTramontinADGarcia-VerdugoJMAlvarez-BuyllaA.2005. Adult ependymal cells are postmitotic and are derived from radial glial cells during embryogenesis. J Neurosci25(1):10–8.
71.
SrinivasanKLeoneDPBatesonRKDobrevaGKohwiYKohwi-ShigematsuT, and others. 2012. A network of genetic repression and derepression specifies projection fates in the developing neocortex. Proc Natl Acad Sci U S A109(47):19071–8.
72.
TramontinADGarcia-VerdugoJMLimDAAlvarez-BuyllaA.2003. Postnatal development of radial glia and the ventricular zone (VZ): a continuum of the neural stem cell compartment. Cereb Cortex13(6):580–7.
73.
van HandelMSwaabHde VriesLSJongmansMJ. 2007. Long-term cognitive and behavioral consequences of neonatal encephalopathy following perinatal asphyxia: a review. Eur J Pediatr166(7):645–54.
74.
VannucciSJHagbergH.2004. Hypoxia-ischemia in the immature brain. J Exp Biol207(18):3149–54.
75.
WinpennyELebel-PotterMFernandezMEBrillMSGotzMGuillemotF, and others. 2011. Sequential generation of olfactory bulb glutamatergic neurons by Neurog2-expressing precursor cells. Neural Dev6:12.
76.
YangZCoveyMVBitelCLNiLJonakaitGMLevisonSW. 2007. Sustained neocortical neurogenesis after neonatal hypoxic/ischemic injury. Ann Neurol61(3):199–208.
77.
YongVWMoumdjianRYongFPRuijsTCFreedmanMSCashmanN, and others. 1991. Gamma-interferon promotes proliferation of adult human astrocytes in vitro and reactive gliosis in the adult mouse brain in vivo. Proc Natl Acad Sci U S A88(16):7016–20.
78.
YoungKMFogartyMKessarisNRichardsonWD. 2007. Subventricular zone stem cells are heterogeneous with respect to their embryonic origins and neurogenic fates in the adult olfactory bulb. J Neurosci27(31):8286–96.
