Gypenosides pre‐treatment protects the brain against cerebral ischemia and increases neural stem cells/progenitors in the subventricular zone

Glioblastoma usually recurs after therapy consisting of surgery, radiotherapy, and chemotherapy. Recurrence is at least partly caused by glioblastoma stem cells (GSCs) that are maintained in intratumoral hypoxic peri-arteriolar microenvironments, or niches, in a slowly dividing state that renders GSCs resistant to radiotherapy and chemotherapy. Because the subventricular zone (SVZ) is a major niche for neural stem cells (NSCs) in the brain, we investigated whether GSCs are present in the SVZ at distance from the glioblastoma tumor. We characterized the SVZ of brains of seven glioblastoma patients using fluorescence immunohistochemistry and image analysis. NSCs were identified by CD133 and SOX2 but not CD9 expression, whereas GSCs were positive for all three biomarkers. NSCs were present in all seven samples and GSCs in six out of seven samples. The SVZ in all samples were hypoxic and expressed the same relevant chemokines and their receptors as GSC niches in glioblastoma tumors: stromal-derived factor-1α (SDF-1α), C-X-C receptor type 4 (CXCR4), osteopontin, and CD44. In conclusion, in glioblastoma patients, GSCs are present at distance from the glioblastoma tumor in the SVZ. These findings suggest that GSCs in the SVZ niche are protected against radiotherapy and chemotherapy and protected against surgical resection due to their distant localization and thus may contribute to tumor recurrence after therapy.

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Neuroprotective properties of the C-Jun N-terminal kinase (JNK) inhibitor in hypoxic hypoxia

Bulletin of Siberian Medicine ◽

10.20538/1682-0363-2019-2-80-88 ◽

2019 ◽

Vol 18 (2) ◽

pp. 80-88

Author(s):

G. N. Zyuz’kov ◽

E. V. Udut ◽

L. A. Miroshnichenko ◽

T. Ju. Poljakova ◽

E. V. Simanina ◽

...

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Subventricular Zone ◽

Nerve Tissue ◽

Hypoxic Exposure ◽

Experimental Animals ◽

Neuronal Stem Cells ◽

Orientation And Exploratory Behavior ◽

The Brain

The aim of the study was to reveal the influence of the JNK inhibitor on the induction of disturbances in the psychoneurological status of experimental animals in the modeling of posthypoxic encephalopathy and to reveal the mechanisms of its action related to the functioning of the neural stem cells of the brain. Materials and methods. The experiments were performed on 64 male outbred mice. Posthypoxic encephalopathy was modeled in non-native mice with hypoxia of the hermetic volume. The JNK inhibitor was administered to mice subcutaneously at a dose of 15 mg/kg once before hypoxic exposure. We studied the neuropsychiatric status, the content of neuronal stem cells in the subventricular zone of the brain of experimental animals, and the direct effect of the JNK inhibitor on intact neural stem cells in vitro. Results. The expressed cerebroprotective action of the pharmacological agent was revealed, which consisted of normalizing the indices of orientation and exploratory behavior and conditioned activity in experimental animals. These effects developed against a background of a significant increase in the content of neural stem cells in the subventricular zone of the brain. In the experiments in vitro, a direct stimulating effect of the JNK inhibitor on neural stem cells was found. Conclusions. The obtained results showed a neuroprotective action of the JNK inhibitor. At the same time, the prevention and compensation of the development of disturbances in the activity of the central nervous system is based on the preservation of the ability of the nerve tissue to repair andassociated with the functioning of resident neural stem cells.

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Polymeric Nanoparticles to Control the Differentiation of Neural Stem Cells in the Subventricular Zone of the Brain

ACS Nano ◽

10.1021/nn304541h ◽

2012 ◽

Vol 6 (12) ◽

pp. 10463-10474 ◽

Cited By ~ 65

Author(s):

Tiago Santos ◽

Raquel Ferreira ◽

João Maia ◽

Fabienne Agasse ◽

Sara Xapelli ◽

...

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Subventricular Zone ◽

Polymeric Nanoparticles ◽

The Brain

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THE SUBVENTRICULAR ZONE IS A SOURCE OF NEURAL STEM CELLS THAT REMODEL THE BRAIN FOLLOWING TRAUMATIC BRAIN INJURY

Critical Care Medicine ◽

10.1097/00003246-200212001-00046 ◽

2002 ◽

Vol 30 (Supplement) ◽

pp. A13

Author(s):

Pritam Ghosh ◽

Haitham Salman ◽

Steven G Kernie

Keyword(s):

Traumatic Brain Injury ◽

Stem Cells ◽

Brain Injury ◽

Neural Stem Cells ◽

Subventricular Zone ◽

The Brain

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Faculty Opinions recommendation of Radial glia give rise to adult neural stem cells in the subventricular zone.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1022935.264691 ◽

2004 ◽

Author(s):

Sally Temple

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Subventricular Zone ◽

Radial Glia ◽

Adult Neural Stem Cells

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Neural Stem Cells: What Happens When They Go Viral?

Viruses ◽

10.3390/v13081468 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1468

Author(s):

Yashika S. Kamte ◽

Manisha N. Chandwani ◽

Alexa C. Michaels ◽

Lauren A. O’Donnell

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Viral Infections ◽

Wide Spectrum ◽

Cell Types ◽

Developmental Abnormalities ◽

Multipotent Progenitor Cells ◽

The Central Nervous System ◽

Simplex Virus ◽

The Brain

Viruses that infect the central nervous system (CNS) are associated with developmental abnormalities as well as neuropsychiatric and degenerative conditions. Many of these viruses such as Zika virus (ZIKV), cytomegalovirus (CMV), and herpes simplex virus (HSV) demonstrate tropism for neural stem cells (NSCs). NSCs are the multipotent progenitor cells of the brain that have the ability to form neurons, astrocytes, and oligodendrocytes. Viral infections often alter the function of NSCs, with profound impacts on the growth and repair of the brain. There are a wide spectrum of effects on NSCs, which differ by the type of virus, the model system, the cell types studied, and the age of the host. Thus, it is a challenge to predict and define the consequences of interactions between viruses and NSCs. The purpose of this review is to dissect the mechanisms by which viruses can affect survival, proliferation, and differentiation of NSCs. This review also sheds light on the contribution of key antiviral cytokines in the impairment of NSC activity during a viral infection, revealing a complex interplay between NSCs, viruses, and the immune system.

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Circular RNA TTC3 regulates cerebral ischemia-reperfusion injury and neural stem cells by miR-372-3p/TLR4 axis in cerebral infarction

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02187-y ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Bo Yang ◽

Li’e Zang ◽

Jingwen Cui ◽

Linlin Wei

Keyword(s):

Stem Cells ◽

Cerebral Ischemia ◽

Cerebral Infarction ◽

Neural Stem Cells ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Luciferase Reporter ◽

Circular Rnas ◽

Cerebral Ischemia Reperfusion ◽

The Impact

Abstract Background Stroke serves as a prevalent cerebrovascular disorder with severe cerebral ischemia/reperfusion (CIR) injury, in which neural stem cells (NSCs) play critical roles in the recovery of cerebral function. Circular RNAs (circRNAs) have been widely found to participate in stroke and NSC modulation. However, the role of circRNA TTC3 (circTTC3) in the regulation of CIR injury and NSCs remains elusive. Here, we aimed to explore the impact of circTTC3 on CIR injury and NSCs. Methods The middle cerebral artery occlusion/repression (MCAO/R) model was established in C57BL/6J mice. The primary astrocytes were isolated from the cerebellum from C57BL/6J mice. The primary NSCs were obtained from rat embryos. The effect of circTTC3 on CIR injury and NSCs was analyzed by TTC staining, qPCR, Western blot, LDH colorimetric kits, MTT assays, Annexin V-FITC Apoptosis Detection Kit, luciferase reporter gene assays, and others in the system. Results Significantly, the expression of circTTC3 was elevated in the MCAO/R mice and oxygen and glucose deprivation (OGD)-treated astrocytes. The depletion of circTTC3 attenuated cerebral infarction, neurological score, and brain water content. The OGD treatment induced apoptosis and the levels of lactate dehydrogenase (LDH) in the astrocytes, in which circTTC3 depletion reduced this phenotype in the system. Moreover, the depletion of circTTC3 promoted the proliferation and upregulated the nestin and β-tubulin III expression in NSCs. Mechanically, circTTC3 was able to sponge miR-372-3p, and miR-372-3p can target Toll-like receptor 4 (TLR4) in NSCs. The miR-372-3p inhibitor or TLR4 overexpression could reverse circTTC3 depletion-mediated astrocyte OGD injury and NSC regulation. Conclusion Thus, we conclude that circTTC3 regulates CIR injury and NSCs by the miR-372-3p/TLR4 axis in cerebral infarction. Our finding presents new insight into the mechanism by which circTTC3 modulates CIR injury and NSC dysfunction. CircTTC3, miR-372-3p, and TLR4 may serve as potential targets for the treatment of CIR injury during stroke.

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