Editorial: Neural Stem Cells of the Subventricular Zone: From Neurogenesis to Glioblastoma Origin

Abstract Background: Recently, the number of neonatal patients receiving surgery under general anesthesia has increased. Ketamine disrupts the proliferation and differentiation of developing neural stem cells (NSCs). Therefore, the safe use of ketamine in pediatric anesthesia has been an issue of increasing concern among anesthesiologists and the children’s parents. Dexmedetomidine (DEX) is widely used in sedation, as an antianxiety agent and for analgesia. DEX has recently been shown to provide neuroprotection against anesthetic-induced neurotoxicity in the developing brain. The aim of this in vivo study was to investigate whether DEX exerted neuroprotective effects on the proliferation and differentiation of NSCs in the subventricular zone (SVZ) following neonatal ketamine exposure. Methods: Postnatal day 7 (PND-7) male Sprague-Dawley rats were equally divided into the following 5 groups: Control group (n=8), Ketamine group (n=8), 1 μg/kg DEX+Ketamine group (n=8), 5 μg/kg DEX+Ketamine group (n=8) and 10 μg/kg DEX+Ketamine group (n=8). The proliferation and differentiation of NSCs in the SVZ were assessed using immunostaining with BrdU incorporation. The levels of Nestin and β-tubulin III in the SVZ were measured using Western blot analyses. Apoptosis was assessed by detecting the levels of the cleaved caspase-3 protein using Western blotting. Results: Neonatal ketamine exposure significantly inhibited NSC proliferation and astrocytic differentiation in the SVZ, and neuronal differentiation was markedly increased. Furthermore, pretreatment with moderate (5 μg/kg) or high doses (10 μg/kg) of DEX reversed the ketamine-induced disturbances in the proliferation and differentiation of NSCs. Meanwhile, neonatal ketamine exposure significantly decreased the expression of Nestin and increased the expression of β-tubulin III in the SVZ compared with the Control group. Treatment with 10 μg/kg DEX notably reversed the ketamine-induced changes in the levels of Nestin and β-tubulin III. In addition, a pretreatment with 10 μg/kg DEX before ketamine anesthesia prevented apoptosis in the SVZ induced by neonatal ketamine exposure. Conclusions: Based on our findings, DEX may exert neuroprotective effects on the proliferation and differentiation of NSCs in the SVZ of neonatal rats in a repeated ketamine anesthesia model.

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Egr-1 is a Critical Regulator of EGF-Receptor-Mediated Expansion of Subventricular Zone Neural Stem Cells and Progenitors During Recovery from Hypoxia–Hypoglycemia

ASN NEURO ◽

10.1042/an20120032 ◽

2013 ◽

Vol 5 (3) ◽

pp. AN20120032 ◽

Cited By ~ 10

Author(s):

Dhivyaa Alagappan ◽

Murugabaskar Balan ◽

Yuhui Jiang ◽

Rachel B. Cohen ◽

Sergei V. Kotenko ◽

...

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Subventricular Zone ◽

Egf Receptor

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Differentiation Induction as a Response to Irradiation in Neural Stem Cells In Vitro

Cancers ◽

10.3390/cancers11070913 ◽

2019 ◽

Vol 11 (7) ◽

pp. 913 ◽

Cited By ~ 6

Author(s):

Jana Konířová ◽

Lukáš Cupal ◽

Šárka Jarošová ◽

Anna Michaelidesová ◽

Jana Vachelová ◽

...

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Brain Cancer ◽

Subventricular Zone ◽

Transcriptional Activity ◽

Radiation Induced ◽

Induction Of Differentiation ◽

Stem Cell Populations ◽

Neurocognitive Decline

Radiotherapy plays a significant role in brain cancer treatment; however, the use of this therapy is often accompanied by neurocognitive decline that is, at least partially, a consequence of radiation-induced damage to neural stem cell populations. Our findings describe features that define the response of neural stem cells (NSCs) to ionizing radiation. We investigated the effects of irradiation on neural stem cells isolated from the ventricular-subventricular zone of mouse brain and cultivated in vitro. Our findings describe the increased transcriptional activity of p53 targets and proliferative arrest after irradiation. Moreover, we show that most cells do not undergo apoptosis after irradiation but rather cease proliferation and start a differentiation program. Induction of differentiation and the demonstrated potential of irradiated cells to differentiate into neurons may represent a mechanism whereby damaged NSCs eliminate potentially hazardous cells and circumvent the debilitating consequences of cumulative DNA damage.

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Neural Stem Cells in the Subventricular Zone are Resilient to Hypoxia/Ischemia whereas Progenitors are Vulnerable

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/01.wcb.0000123906.17746.00 ◽

2004 ◽

Vol 24 (7) ◽

pp. 814-825 ◽

Cited By ~ 78

Author(s):

Michael J. Romanko ◽

Raymond P. Rothstein ◽

Steven W. Levison

Keyword(s):

Electron Microscopy ◽

Stem Cells ◽

Neural Stem Cells ◽

Subventricular Zone ◽

Caspase 3 ◽

Hybrid Cell ◽

Terminal Deoxynucleotidyl Transferase ◽

Neurologic Disability ◽

Hematoxylin And Eosin ◽

Dying Cells

Perinatal hypoxic-ischemic (H/I) brain injury remains a major cause of neurologic disability. Because we have previously demonstrated that this insult depletes cells from the subventricular zone (SVZ), the goal of the present investigation was to compare the relative vulnerability to H/I of neural stem cells versus progenitors. The dorsolateral SVZs of P6 rats were examined at 2 to 48 hours of recovery from H/I using hematoxylin and eosin, in situ end labeling (ISEL), terminal deoxynucleotidyl transferase-mediated 2′-deoxyuridine 5′-triphosphate-biotin nick end labeling (TUNEL), electron microscopy, and immunofluorescence. Pyknotic nuclei and ISEL+ cells were observed by 4 hours of recovery, peaked at 12 hours, and persisted for at least 48 hours. Many active-caspase3+ cells were observed at 12 hours and they comprised one third of the total TUNEL+ population. Electron microscopy revealed that hybrid cell deaths predominated at 12 hours of recovery. Importantly, few dying cells were observed in the medial SVZ, where putative stem cells reside, and no nestin+ medial SVZ cells showed caspase-3 activation. By contrast, active-caspase-3+/PSA-NCAM+ progenitors were prominent in the lateral SVZ. These data demonstrate that early progenitors are vulnerable to H/I, whereas neural stem cells are resilient. The demise of these early progenitors may lead to the depletion of neuronal and late oligodendrocyte progenitors, contributing to cerebral dysgenesis after perinatal insults.

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Adult subventricular zone neural stem cells as a potential source of dopaminergic replacement neurons

Frontiers in Neuroscience ◽

10.3389/fnins.2014.00016 ◽

2014 ◽

Vol 8 ◽

Cited By ~ 22

Author(s):

John W. Cave ◽

Meng Wang ◽

Harriet Baker

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Subventricular Zone ◽

Potential Source

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193 ROBUST PROPAGATION OF SELF-RENEWING PORCINE NEURAL STEM CELLS ISOLATED FROM TRANSGENIC PIGS WITH A GFAP-CreERT2 SYSTEM CAPABLE OF CONTROLLING THE EXPRESSION OF EGFP GENES

Reproduction Fertility and Development ◽

10.1071/rdv29n1ab193 ◽

2017 ◽

Vol 29 (1) ◽

pp. 205

Author(s):

E. Kim ◽

H. Kim ◽

S.-H. Hyun

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Subventricular Zone ◽

Central Nervous System Diseases ◽

Transgenic Pigs ◽

Ample Evidence ◽

Viable Cells ◽

Promising Source ◽

Dna Recombinase

Ample evidence has demonstrated the important roles of pigs because their anatomical, immunologic, and physiological characteristics are fairly similar to humans. In particular, their gyrencephalic brain are more comparable to humans than rodents with similar grey and white matter composition and size. In this study, we isolated and propagated the neural stem cells (GFAP-CreERT2-NSCs) from the transgenic piglet with expression of CreERT2, a fusion protein of the DNA recombinase Cre and mutated ligand-binding domain of the human oestrogen receptor, under the control of the GFAP promoter. The primary culture from tissue of porcine CreERT2 brain led to floating spherical masses of cells that revealed similar morphology and size distribution to neurospheres reported by previous studies. Quantitative analysis indicated a yield of 2.50 ± 0.44 primary spheres per 1,000 viable cells from the neocortex, versus 12.92 ± 1.67 primary spheres per 1,000 viable cells from the periventricular region (PVR) including subventricular zone. Secondary spheres (6.67 ± 1.10 spheres from neocortex versus 23.08 ± 1.96 spheres from PVR cells) were formed from primary spheres at 10 days after passage. Tertiary spheres (8.42 ± 0.99 spheres from neocortex versus 23.08 ± 1.91 spheres from PVR cells) could also be obtained after a second passage, indicating that they were proliferating in vitro. The CreERT2-NSCs showed normal 36+XY karyotype and representative NSC markers, such as NESTIN, SOX2, and VIMENTIN. After differentiation, we were able to obtain populations of astrocytes and neurons expressing GFAP and TUJ1, respectively. In summary, we verified and propagated the isolated GFAP promoter-driven CreERT2-NSCs, which would be considered a promising source of cells for treatment of central nervous system diseases.

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