Modulating endogenous regenerative processes may represent a suitable treatment for central nervous system (CNS) injuries, such as stroke or trauma. Neural stem/progenitor cells (NS/PCs), which naturally reside in the subventricular zone (SVZ) of the adult brain, proliferate and differentiate to other cell types, and therefore may compensate the negative consequences of ischemic injury. The fate of NS/PCs in the developing brain is largely influenced by Wingless/Integrated (Wnt) signaling; however, its role in the differentiation of adult NS/PCs under ischemic conditions is still enigmatic. In our previous study, we identified the Wnt/β-catenin signaling pathway as a factor promoting neurogenesis at the expense of gliogenesis in neonatal mice. In this study, we used adult transgenic mice in order to assess the impact of the canonical Wnt pathway modulation (inhibition or hyper-activation) on NS/PCs derived from the SVZ, and combined it with the middle cerebral artery occlusion (MCAO) to disclose the effect of focal cerebral ischemia (FCI). Based on the electrophysiological properties of cultured cells, we first identified three cell types that represented in vitro differentiated NS/PCs - astrocytes, neuron-like cells, and precursor cells. Following FCI, we detected fewer neuron-like cells after Wnt signaling inhibition. Furthermore, the immunohistochemical analysis revealed an overall higher expression of cell-type-specific proteins after FCI, indicating increased proliferation and differentiation rates of NS/PCs in the SVZ. Remarkably, Wnt signaling hyper-activation increased the abundance of proliferating and neuron-like cells, while Wnt pathway inhibition had the opposite effect. Finally, the expression profiling at the single cell level revealed an increased proportion of neural stem cells and neuroblasts after FCI. These observations indicate that Wnt signaling enhances NS/PCs-based regeneration in the adult mouse brain following FCI, and supports neuronal differentiation in the SVZ.

2nd Faculty of Medicine Charles University Prague Czechia

Department of Cellular Neurophysiology Institute of Experimental Medicine Czech Academy of Sciences Prague Czechia

Division of Experimental Therapeutics Graduate School of Medicine Kyoto University Kyoto Japan

Laboratory of Cell and Developmental Biology Institute of Molecular Genetics Czech Academy of Sciences Prague Czechia

Laboratory of Transcriptional Regulation Institute of Molecular Genetics Czech Academy of Sciences Prague Czechia

Service Laboratory of Light Microscopy Institute of Molecular Genetics Czech Academy of Sciences Prague Czechia

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Adachi K., Mirzadeh Z., Sakaguchi M., Yamashita T., Nikolcheva T., Gotoh Y., et al. (2007). Beta-catenin signaling promotes proliferation of progenitor cells in the adult mouse subventricular zone. Stem Cells 25 2827–2836. PubMed

Altman J., Das G. D. (1965). Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. J. Comp. Neurol. 124 319–335. PubMed

Bänziger C., Soldini D., Schütt C., Zipperlen P., Hausmann G., Basler K. (2006). Wntless, a conserved membrane protein dedicated to the secretion of Wnt proteins from signaling cells. Cell 125 509–522. 10.1016/j.cell.2006.02.049 PubMed DOI

Bataveljić D., Nikolić L., Milosević M., Todorović N., Andjus P. R. (2012). Changes in the astrocytic aquaporin-4 and inwardly rectifying potassium channel expression in the brain of the amyotrophic lateral sclerosis SOD1(G93A) rat model. Glia 60 1991–2003. 10.1002/glia.22414 PubMed DOI

Belov Kirdajova D., Kriska J., Tureckova J., Anderova M. (2020). Ischemia-triggered glutamate excitotoxicity from the perspective of Glial cells. Front. Cell. Neurosci. 14:51. 10.3389/fncel.2020.00051 PubMed DOI PMC

Bizen N., Inoue T., Shimizu T., Tabu K., Kagawa T., Taga T. (2014). A growth-promoting signaling component cyclin D1 in neural stem cells has antiastrogliogenic function to execute self-renewal. Stem Cells 32 1602–1615. 10.1002/stem.1613 PubMed DOI

Boehme A. K., Esenwa C., Elkind M. S. (2017). Stroke risk factors, genetics, and prevention. Circ. Res. 120 472–495. 10.1161/CIRCRESAHA.116.308398 PubMed DOI PMC

Borday C., Parain K., Thi Tran H., Vleminckx K., Perron M., Monsoro-Burq A. H. (2018). An atlas of Wnt activity during embryogenesis in Xenopus tropicalis. PLoS One 13:e0193606. 10.1371/journal.pone.0193606 PubMed DOI PMC

Bowman A. N., van Amerongen R., Palmer T. D., Nusse R. (2013). Lineage tracing with Axin2 reveals distinct developmental and adult populations of Wnt/β-catenin-responsive neural stem cells. Proc. Natl. Acad. Sci. U.S.A. 110 7324–7329. 10.1073/pnas.1305411110 PubMed DOI PMC

Buffo A., Rite I., Tripathi P., Lepier A., Colak D., Horn A.-P., et al. (2008). Origin and progeny of reactive gliosis: a source of multipotent cells in the injured brain. Proc. Natl. Acad. Sci. U.S.A. 105 3581–3586. 10.1073/pnas.0709002105 PubMed DOI PMC

Butti E., Bacigaluppi M., Chaabane L., Ruffini F., Brambilla E., Berera G., et al. (2019). Neural stem cells of the subventricular zone contribute to neuroprotection of the corpus callosum after cuprizone-induced demyelination. J. Neurosci. 39 5481–5492. 10.1523/JNEUROSCI.0227-18.2019 PubMed DOI PMC

Carpenter A. C., Rao S., Wells J. M., Campbell K., Lang R. A. (2010). Generation of mice with a conditional null allele for Wntless. Genesis 48 554–558. 10.1002/dvg.20651 PubMed DOI PMC

Charles University (2020). Thesis Repository. Available online at: https://is.cuni.cz/webapps/zzp (accessed October 30, 2020).

Chenn A., Walsh C. A. (2002). Regulation of cerebral cortical size by control of cell cycle exit in neural precursors. Science 297 365–369. 10.1126/science.1074192 PubMed DOI

Chodelkova O., Masek J., Korinek V., Kozmik Z., Machon O. (2018). Tcf7L2 is essential for neurogenesis in the developing mouse neocortex. Neural Dev. 13:8. 10.1186/s13064-018-0107-8 PubMed DOI PMC

Codega P., Silva-Vargas V., Paul A., Maldonado-Soto A. R., Deleo A. M., Pastrana E., et al. (2014). Prospective identification and purification of quiescent adult neural stem cells from their in vivo niche. Neuron 82 545–559. 10.1016/j.neuron.2014.02.039 PubMed DOI PMC

Colak G., Filiano A. J., Johnson G. V. W. (2011). The application of permanent middle cerebral artery ligation in the mouse. J. Vis. Exp. 53:3039. 10.3791/3039 PubMed DOI PMC

Cui X. P., Xing Y., Chen J. M., Dong S. W., Ying D. J., Yew D. T. (2011). Wnt/beta-catenin is involved in the proliferation of hippocampal neural stem cells induced by hypoxia. Ir. J. Med. Sci. 180 387–393. 10.1007/s11845-010-0566-3 PubMed DOI

Daneman R., Agalliu D., Zhou L., Kuhnert F., Kuo C. J., Barres B. A. (2009). Wnt/beta-catenin signaling is required for CNS, but not non-CNS, angiogenesis. Proc. Natl. Acad. Sci. U.S.A. 106 641–646. 10.1073/pnas.0805165106 PubMed DOI PMC

Encinas J. M., Michurina T. V., Peunova N., Park J. H., Tordo J., Peterson D. A., et al. (2011). Division-coupled astrocytic differentiation and age-related depletion of neural stem cells in the adult hippocampus. Cell Stem Cell 8 566–579. 10.1016/j.stem.2011.03.010 PubMed DOI PMC

Furutachi S., Matsumoto A., Nakayama K. I., Gotoh Y. (2013). p57 controls adult neural stem cell quiescence and modulates the pace of lifelong neurogenesis. EMBO J. 32 970–981. 10.1038/emboj.2013.50 PubMed DOI PMC

Ginsberg M. D. (2003). Adventures in the pathophysiology of brain ischemia: penumbra, gene expression, neuroprotection: the 2002 Thomas Willis Lecture. Stroke 34 214–223. PubMed

Groves N., O’Keeffe I., Lee W., Toft A., Blackmore D., Bandhavkar S., et al. (2019). Blockade of TrkB but not p75NTR activates a subpopulation of quiescent neural precursor cells and enhances neurogenesis in the adult mouse hippocampus. Dev. Neurobiol. 79 868–879. 10.1002/dneu.22729 PubMed DOI

Harada N., Tamai Y., Ishikawa T., Sauer B., Takaku K., Oshima M., et al. (1999). Intestinal polyposis in mice with a dominant stable mutation of the beta-catenin gene. EMBO J. 18 5931–5942. PubMed PMC

Hernandez-Encarnacion L., Sharma P., Simon R., Zhou A. (2017). Condition-specific transcriptional regulation of neuronal ion channel genes in brain ischemia. Int. J. Physiol. Pathophysiol. Pharmacol. 9 192–201. PubMed PMC

Higashimori H., Sontheimer H. (2007). Role of Kir4.1 channels in growth control of glia. Glia 55 1668–1679. 10.1002/glia.20574 PubMed DOI PMC

Honsa P., Pivonkova H., Anderova M. (2013). Focal cerebral ischemia induces the neurogenic potential of mouse Dach1-expressing cells in the dorsal part of the lateral ventricles. Neuroscience 240 39–53. 10.1016/j.neuroscience.2013.02.048 PubMed DOI

Honsa P., Pivonkova H., Dzamba D., Filipova M., Anderova M. (2012). Polydendrocytes display large lineage plasticity following focal cerebral ischemia. PLoS One 7:e36816. 10.1371/journal.pone.0036816 PubMed DOI PMC

Honsa P., Pivonkova H., Harantova L., Butenko O., Kriska J., Dzamba D., et al. (2014). Increased expression of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in reactive astrocytes following ischemia. Glia 62 2004–2021. 10.1002/glia.22721 PubMed DOI

Hurn P. D., Macrae I. M. (2000). Estrogen as a neuroprotectant in stroke. J. Cereb. Blood Flow Metab. 20 631–652. PubMed

Janeckova L., Fafilek B., Krausova M., Horazna M., Vojtechova M., Alberich-Jorda M., et al. (2016). Wnt signaling inhibition deprives small intestinal stem cells of clonogenic capacity. Genesis 54 101–114. 10.1002/dvg.22922 PubMed DOI PMC

Johe K. K., Hazel T. G., Muller T., Dugich-Djordjevic M. M., McKay R. D. (1996). Single factors direct the differentiation of stem cells from the fetal and adult central nervous system. Genes Dev. 10 3129–3140. PubMed

Kalamakis G., Brüne D., Ravichandran S., Bolz J., Fan W., Ziebell F., et al. (2019). Quiescence modulates stem cell maintenance and regenerative capacity in the aging brain. Cell 176 1407–1419.e14. 10.1016/j.cell.2019.01.040 PubMed DOI

Kalani M. Y., Cheshier S. H., Cord B. J., Bababeygy S. R., Vogel H., Weissman I. L., et al. (2008). Wnt-mediated self-renewal of neural stem/progenitor cells. Proc. Natl. Acad. Sci. U.S.A. 105 16970–16975. 10.1073/pnas.0808616105 PubMed DOI PMC

Kase Y., Otsu K., Shimazaki T., Okano H. (2019). Involvement of p38 in age-related decline in adult neurogenesis via modulation of Wnt signaling. Stem Cell Rep. 12 1313–1328. 10.1016/j.stemcr.2019.04.010 PubMed DOI PMC

Kelly K. F., Ng D. Y., Jayakumaran G., Wood G. A., Koide H., Doble B. W. (2011). β-catenin enhances Oct-4 activity and reinforces pluripotency through a TCF-independent mechanism. Cell Stem Cell 8 214–227. 10.1016/j.stem.2010.12.010 PubMed DOI PMC

Knotek T., Janeckova L., Kriska J., Korinek V., Anderova M. (2020). Glia and neural stem and progenitor cells of the healthy and ischemic brain: the workplace for the Wnt signaling pathway. Genes 11:804. 10.3390/genes11070804 PubMed DOI PMC

Kokaia Z., Thored P., Arvidsson A., Lindvall O. (2006). Regulation of stroke-induced neurogenesis in adult brain–recent scientific progress. Cereb. Cortex 16 (Suppl. 1), i162–i167. PubMed

Kriska J., Honsa P., Dzamba D., Butenko O., Kolenicova D., Janeckova L., et al. (2016). Manipulating Wnt signaling at different subcellular levels affects the fate of neonatal neural stem/progenitor cells. Brain Res. 1651 73–87. 10.1016/j.brainres.2016.09.026 PubMed DOI

Lamus F., Martín C., Carnicero E., Moro J. A., Fernández J. M. F., Mano A., et al. (2020). FGF2/EGF contributes to brain neuroepithelial precursor proliferation and neurogenesis in rat embryos: the involvement of embryonic cerebrospinal fluid. Dev. Dyn. 249 141–153. 10.1002/dvdy.135 PubMed DOI

Lembach A., Stahr A., Ali A. A. H., Ingenwerth M., von Gall C. (2018). Sex-dependent effects of Bmal1-deficiency on mouse cerebral cortex infarction in response to photothrombotic stroke. Int. J. Mol. Sci. 19:3124. 10.3390/ijms19103124 PubMed DOI PMC

Li L., Harms K. M., Ventura P. B., Lagace D. C., Eisch A. J., Cunningham L. A. (2010). Focal cerebral ischemia induces a multilineage cytogenic response from adult subventricular zone that is predominantly gliogenic. Glia 58 1610–1619. 10.1002/glia.21033 PubMed DOI PMC

Lie D. C., Colamarino S. A., Song H. J., Désiré L., Mira H., Consiglio A., et al. (2005). Wnt signalling regulates adult hippocampal neurogenesis. Nature 437 1370–1375. PubMed

Llorens-Bobadilla E., Zhao S., Baser A., Saiz-Castro G., Zwadlo K., Martin-Villalba A. (2015). Single-cell transcriptomics reveals a population of dormant neural stem cells that become activated upon brain injury. Cell Stem Cell 17 329–340. 10.1016/j.stem.2015.07.002 PubMed DOI

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 6 445–456. 10.1016/j.stem.2010.03.017 PubMed DOI

Lupo G., Gioia R., Nisi P. S., Biagioni S., Cacci E. (2019). Molecular mechanisms of neurogenic aging in the adult mouse subventricular zone. J. Exp. Neurosci. 13:1179069519829040. 10.1177/1179069519829040 PubMed DOI PMC

Machon O., Backman M., Machonova O., Kozmik Z., Vacik T., Andersen L., et al. (2007). A dynamic gradient of Wnt signaling controls initiation of neurogenesis in the mammalian cortex and cellular specification in the hippocampus. Dev. Biol. 311 223–237. 10.1016/j.ydbio.2007.08.038 PubMed DOI

Machon O., van den Bout C. J., Backman M., Kemler R., Krauss S. (2003). Role of beta-catenin in the developing cortical and hippocampal neuroepithelium. Neuroscience 122 129–143. 10.1016/s0306-4522(03)00519-0 PubMed DOI

Mastrodonato A., Barbati S. A., Leone L., Colussi C., Gironi K., Rinaudo M., et al. (2018). Olfactory memory is enhanced in mice exposed to extremely low-frequency electromagnetic fields via Wnt/β-catenin dependent modulation of subventricular zone neurogenesis. Sci. Rep. 8:262. PubMed PMC

Mikels A. J., Nusse R. (2006). Purified Wnt5a protein activates or inhibits beta-catenin-TCF signaling depending on receptor context. PLoS Biol. 4:e115. 10.1371/journal.pbio.0040115 PubMed DOI PMC

Mira H., Andreu Z., Suh H., Lie D. C., Jessberger S., Consiglio A., et al. (2010). Signaling through BMPR-IA regulates quiescence and long-term activity of neural stem cells in the adult hippocampus. Cell Stem Cell 7 78–89. 10.1016/j.stem.2010.04.016 PubMed DOI

Mizrak D., Levitin H. M., Delgado A. C., Crotet V., Yuan J., Chaker Z., et al. (2019). Single-cell analysis of regional differences in Adult V-SVZ neural stem cell lineages. cell Rep. 26 394–406.e5. 10.1016/j.celrep.2018.12.044 PubMed DOI PMC

Morrison S. J., Spradling A. C. (2008). Stem cells and niches: mechanisms that promote stem cell maintenance throughout life. Cell 132 598–611. 10.1016/j.cell.2008.01.038 PubMed DOI PMC

Nusse R., Clevers H. (2017). Wnt/β-catenin signaling, disease, and emerging therapeutic modalities. Cell 169 985–999. 10.1016/j.cell.2017.05.016 PubMed DOI

Obernier K., Alvarez-Buylla A. (2019). Neural stem cells: origin, heterogeneity and regulation in the adult mammalian brain. Development 146 dev156059. 10.1242/dev.156059 PubMed DOI PMC

O’Keeffe G. C., Tyers P., Aarsland D., Dalley J. W., Barker R. A., Caldwell M. A. (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 8754–8759. 10.1073/pnas.0803955106 PubMed DOI PMC

Palomer E., Buechler J., Salinas P. C. (2019). Wnt signaling deregulation in the aging and Alzheimer’s brain. Front. Cell. Neurosci. 13:227. 10.3389/fncel.2019.00227 PubMed DOI PMC

Pleasure S. J., Collins A. E., Lowenstein D. H. (2000). Unique expression patterns of cell fate molecules delineate sequential stages of dentate gyrus development. J. Neurosci. 20 6095–6105. PubMed PMC

Posokhova E., Shukla A., Seaman S., Volate S., Hilton M. B., Wu B., et al. (2015). GPR124 functions as a WNT7-specific coactivator of canonical β-catenin signaling. Cell Rep. 10 123–130. 10.1016/j.celrep.2014.12.020 PubMed DOI PMC

Prajerova I., Honsa P., Chvatal A., Anderova M. (2010). Distinct effects of sonic hedgehog and Wnt-7a on differentiation of neonatal neural stem/progenitor cells in vitro. Neuroscience 171 693–711. 10.1016/j.neuroscience.2010.09.023 PubMed DOI

Puig B., Brenna S., Magnus T. (2018). Molecular communication of a dying neuron in stroke. Int. J. Mol. Sci. 19:2834. 10.3390/ijms19092834 PubMed DOI PMC

Rajsic S., Gothe H., Borba H. H., Sroczynski G., Vujicic J., Toell T., et al. (2019). Economic burden of stroke: a systematic review on post-stroke care. Eur. J. Health Econ. 20 107–134. 10.1007/s10198-018-0984-0 PubMed DOI

Rossi D. J., Brady J. D., Mohr C. (2007). Astrocyte metabolism and signaling during brain ischemia. Nat. Neurosci. 10 1377–1386. PubMed PMC

Ruzicka J., Machova-Urdzikova L., Gillick J., Amemori T., Romanyuk N., Karova K., et al. (2017). A comparative study of three different types of stem cells for treatment of rat spinal cord injury. Cell Transplant. 26 585–603. 10.3727/096368916X693671 PubMed DOI PMC

Seri B., García-Verdugo J. M., McEwen B. S., Alvarez-Buylla A. (2001). Astrocytes give rise to new neurons in the adult mammalian hippocampus. J. Neurosci. 21 7153–7160. 10.1523/JNEUROSCI.21-18-07153.2001 PubMed DOI PMC

Shruster A., Ben-Zur T., Melamed E., Offen D. (2012). Wnt signaling enhances neurogenesis and improves neurological function after focal ischemic injury. PLoS One 7:e40843. 10.1371/journal.pone.0040843 PubMed DOI PMC

Sierra A., Encinas J. M., Deudero J. J., Chancey J. H., Enikolopov G., Overstreet-Wadiche L. S., et al. (2010). Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis. Cell Stem Cell 7 483–495. 10.1016/j.stem.2010.08.014 PubMed DOI PMC

Stuart T., Butler A., Hoffman P., Hafemeister C., Papalexi E., Mauck W. M., III, et al. (2019). Comprehensive integration of single-cell data. Cell 177 1888–1902.e21. 10.1016/j.cell.2019.05.031 PubMed DOI PMC

ten Berge D., Brugmann S. A., Helms J. A., Nusse R. (2008). Wnt and FGF signals interact to coordinate growth with cell fate specification during limb development. Development 135 3247–3257. 10.1242/dev.023176 PubMed DOI PMC

Urbán N., Guillemot F. (2014). Neurogenesis in the embryonic and adult brain: same regulators, different roles. Front. Cell. Neurosci. 8:396. 10.3389/fncel.2014.00396 PubMed DOI PMC

Valenta T., Hausmann G., Basler K. (2012). The many faces and functions of β-catenin. EMBO J. 31 2714–2736. 10.1038/emboj.2012.150 PubMed DOI PMC

van Amerongen R., Berns A. (2006). Knockout mouse models to study Wnt signal transduction. Trends Genet. 22 678–689. PubMed

van de Moosdijk A. A. A., van de Grift Y. B. C., de Man S. M. A., Zeeman A. L., van Amerongen R. (2020). A novel Axin2 knock-in mouse model for visualization and lineage tracing of WNT/CTNNB1 responsive cells. Genesis 58:e23387. 10.1002/dvg.23387 PubMed DOI PMC

Vancamp P., Gothié J. D., Luongo C., Sébillot A., Le Blay K., Butruille L., et al. (2019). Gender-specific effects of transthyretin on neural stem cell fate in the subventricular zone of the adult mouse. Sci. Rep. 9:19689. 10.1038/s41598-019-56156-w PubMed DOI PMC

Vay S. U., Flitsch L. J., Rabenstein M., Rogall R., Blaschke S., Kleinhaus J., et al. (2018). The plasticity of primary microglia and their multifaceted effects on endogenous neural stem cells in vitro and in vivo. J. Neuroinflammation 15:226. 10.1186/s12974-018-1261-y PubMed DOI PMC

Ventura A., Kirsch D. G., McLaughlin M. E., Tuveson D. A., Grimm J., Lintault L., et al. (2007). Restoration of p53 function leads to tumour regression in vivo. Nature 445 661–665. PubMed

Wallmen B., Schrempp M., Hecht A. (2012). Intrinsic properties of Tcf1 and Tcf4 splice variants determine cell-type-specific Wnt/β-catenin target gene expression. Nucleic Acids Res. 40 9455–9469. 10.1093/nar/gks690 PubMed DOI PMC

Walz W. (2000). Controversy surrounding the existence of discrete functional classes of astrocytes in adult gray matter. Glia 31 95–103. PubMed

Wang J., Fu X., Zhang D., Yu L., Li N., Lu Z., et al. (2017). ChAT-positive neurons participate in subventricular zone neurogenesis after middle cerebral artery occlusion in mice. Behav. Brain Res. 316 145–151. 10.1016/j.bbr.2016.09.007 PubMed DOI PMC

Wiese K. E., Nusse R., van Amerongen R. (2018). Wnt signalling: conquering complexity. Development 145 dev165902. 10.1242/dev.165902 PubMed DOI

Woodruff T. M., Thundyil J., Tang S. C., Sobey C. G., Taylor S. M., Arumugam T. V. (2011). Pathophysiology, treatment, and animal and cellular models of human ischemic stroke. Mol. Neurodegener. 6:11. 10.1186/1750-1326-6-11 PubMed DOI PMC

Wu X., Tu X., Joeng K. S., Hilton M. J., Williams D. A., Long F. (2008). Rac1 activation controls nuclear localization of beta-catenin during canonical Wnt signaling. Cell 133 340–353. 10.1016/j.cell.2008.01.052 PubMed DOI PMC

Yao C., Williams A. J., Cui P., Berti R., Hunter J. C., Tortella F. C., et al. (2002). Differential pattern of expression of voltage-gated sodium channel genes following ischemic brain injury in rats. Neurotox. Res. 4 67–75. PubMed

Zehendner C. M., Sebastiani A., Hugonnet A., Bischoff F., Luhmann H. J., Thal S. C. (2015). Traumatic brain injury results in rapid pericyte loss followed by reactive pericytosis in the cerebral cortex. Sci. Rep. 5:13497. 10.1038/srep13497 PubMed DOI PMC

Zhang R. L., Chopp M., Roberts C., Liu X., Wei M., Nejad-Davarani S. P., et al. (2014). Stroke increases neural stem cells and angiogenesis in the neurogenic niche of the adult mouse. PLoS One 9:e113972. 10.1371/journal.pone.0113972 PubMed DOI PMC

Zhang X., Zhu C., Luo Q., Dong J., Liu L., Li M., et al. (2016). Impact of siRNA targeting of β-catenin on differentiation of rat neural stem cells and gene expression of Ngn1 and BMP4 following in vitro hypoxic-ischemic brain damage. Mol. Med. Rep. 14 3595–3601. 10.3892/mmr.2016.5667 PubMed DOI PMC

Zhang Z., Chopp M. (2016). Neural stem cells and ischemic brain. J. Stroke 18 267–272. PubMed PMC

Zhou M., Xu G., Xie M., Zhang X., Schools G. P., Ma L., et al. (2009). TWIK-1 and TREK-1 are potassium channels contributing significantly to astrocyte passive conductance in rat hippocampal slices. J. Neurosci. 29 8551–8564. 10.1523/JNEUROSCI.5784-08.2009 PubMed DOI PMC

Aryl Hydrocarbon Receptor (AhR)-Mediated Signaling in iPSC-Derived Human Motor Neurons

On the Common Journey of Neural Cells through Ischemic Brain Injury and Alzheimer's Disease