Transplantation of neural progenitor cells stimulates endogenous neurogenesis in mice after ischemic stroke

2014 ◽  
Vol 2 (1) ◽  
pp. 85-89 ◽  
Author(s):  
O. Tsupykov ◽  
V. Kyryk ◽  
A. Mamchur ◽  
P. Poberezhnyi ◽  
G. Butenko ◽  
...  

The researchers have currently been actively investigating the possibilities for transplantation of the stem cells of various sources for treatment of the ischemic and degenerative diseases of the nervous systemInfluence of transplantation of the hippocampal neural progenitor cells (NPCs) on endogenous neurogenesis in the mice after brain ischemia-reperfusion induced by 20 min occlusion of both carotid arteries has been studied. Following 24 hours after occlusion the NPCsisolated from the hippocampus of the FVB-Cg-Tg(GFPU)5Nagy/J mice transgenic by the GFP gene were transplanted stereotactically into hippocampal CA1 area of the experimental animals. For evaluating neurogenesis in the hippocampus of the ischemic animals we used immunohistochemical staining of the brain slices for BrdU and doublecortin (DCX). It has been found that transplantation of neural progenitor cells increased the number of BrdU- and DCX-positive cells in the dentate gyrus of the hippocampus after short-term global ischemia.These data allow admit that NPC transplantation to the ischemic animals influences on endogenous adaptation processes in the brain and on the neurogenesis, in particular.

2018 ◽  
Vol 43 (1) ◽  
pp. 180-189 ◽  
Author(s):  
Kanako Saito ◽  
Ryotaro Kawasoe ◽  
Hiroshi Sasaki ◽  
Ayano Kawaguchi ◽  
Takaki Miyata

Abstract Spatiotemporally ordered production of cells is essential for brain development. Normally, most undifferentiated neural progenitor cells (NPCs) face the apical (ventricular) surface of embryonic brain walls. Pathological detachment of NPCs from the apical surface and their invasion of outer neuronal territories, i.e., formation of NPC heterotopias, can disrupt the overall structure of the brain. Although NPC heterotopias have previously been observed in a variety of experimental contexts, the underlying mechanisms remain largely unknown. Yes-associated protein 1 (Yap1) and the TEA domain (Tead) proteins, which act downstream of Hippo signaling, enhance the stem-like characteristics of NPCs. Elevated expression of Yap1 or Tead in the neural tube (future spinal cord) induces massive NPC heterotopias, but Yap/Tead-induced expansion of NPCs in the developing brain has not been previously reported to produce NPC heterotopias. To determine whether NPC heterotopias occur in a regionally characteristic manner, we introduced the Yap1-S112A or Tead-VP16 into NPCs of the telencephalon and diencephalon, two neighboring but distinct forebrain regions, of embryonic day 10 mice by in utero electroporation, and compared NPC heterotopia formation. Although NPCs in both regions exhibited enhanced stem-like behaviors, heterotopias were larger and more frequent in the diencephalon than in the telencephalon. This result, the first example of Yap/Tead-induced NPC heterotopia in the forebrain, reveals that Yap/Tead-induced NPC heterotopia is not specific to the neural tube, and also suggests that this phenomenon depends on regional factors such as the three-dimensional geometry and assembly of these cells.


2004 ◽  
Vol 153 (1) ◽  
pp. 19-27 ◽  
Author(s):  
Sankar Surendran ◽  
Lamya S. Shihabuddin ◽  
Jennifer Clarke ◽  
Tatyana V. Taksir ◽  
Gregory R. Stewart ◽  
...  

2003 ◽  
Vol 43 (16) ◽  
pp. 1699-1708 ◽  
Author(s):  
Hiroyuki Mizumoto ◽  
Keiko Mizumoto ◽  
Marie A Shatos ◽  
Henry Klassen ◽  
Michael J Young

2018 ◽  
Vol 19 (8) ◽  
pp. 2313 ◽  
Author(s):  
Stefanie Peters ◽  
Michael Paolillo ◽  
Evanthia Mergia ◽  
Doris Koesling ◽  
Lea Kennel ◽  
...  

Impaired NO-cGMP signaling has been linked to several neurological disorders. NO-sensitive guanylyl cyclase (NO-GC), of which two isoforms—NO-GC1 and NO-GC2—are known, represents a promising drug target to increase cGMP in the brain. Drug-like small molecules have been discovered that work synergistically with NO to stimulate NO-GC activity. However, the effects of NO-GC stimulators in the brain are not well understood. In the present study, we used Förster/fluorescence resonance energy transfer (FRET)-based real-time imaging of cGMP in acute brain slices and primary neurons of cGMP sensor mice to comparatively assess the activity of two structurally different NO-GC stimulators, IWP-051 and BAY 41-2272, in the cerebellum, striatum and hippocampus. BAY 41-2272 potentiated an elevation of cGMP induced by the NO donor DEA/NO in all tested brain regions. Interestingly, IWP-051 potentiated DEA/NO-induced cGMP increases in the cerebellum and striatum, but not in the hippocampal CA1 area or primary hippocampal neurons. The brain-region-selective activity of IWP-051 suggested that it might act in a NO-GC isoform-selective manner. Results of mRNA in situ hybridization indicated that the cerebellum and striatum express NO-GC1 and NO-GC2, while the hippocampal CA1 area expresses mainly NO-GC2. IWP-051-potentiated DEA/NO-induced cGMP signals in the striatum of NO-GC2 knockout mice but was ineffective in the striatum of NO-GC1 knockout mice. These results indicate that IWP-051 preferentially stimulates NO-GC1 signaling in brain slices. Interestingly, no evidence for an isoform-specific effect of IWP-051 was observed when the cGMP-forming activity of whole brain homogenates was measured. This apparent discrepancy suggests that the method and conditions of cGMP measurement can influence results with NO-GC stimulators. Nevertheless, it is clear that NO-GC stimulators enhance cGMP signaling in the brain and should be further developed for the treatment of neurological diseases.


Author(s):  
O. M. Tsupykov ◽  
T. A. Pivneva ◽  
A. O. Poddubna ◽  
V. M. Kyryk ◽  
O. V. Kuchuk ◽  
...  

2013 ◽  
Vol 94 (4) ◽  
pp. 831-836 ◽  
Author(s):  
Osamu Kotani ◽  
Kazuya Shirato ◽  
Noriyo Nagata ◽  
Hidetoshi Ikeda ◽  
Kimimasa Takahashi ◽  
...  

A mouse-adapted porcine epidemic diarrhea virus, MK-p10, showed higher neurovirulence in suckling mice than a non-adapted MK strain. There was no difference in virus growth, whereas clear differences between these two virus infections existed in the type of target cells infected, the spread of virus and the cytokine levels produced in the brain. In the early phase of infection, neurons, astrocytes and neural progenitor cells were infected by MK-p10, whereas neural progenitor cells were the only target cells infected by MK. On days 4–5 post-inoculation, MK-p10 antigens were distributed in a number of neurons in a wide area of the brain; however, antigens were restricted in MK infection. In moribund mice in both infection groups, viral antigens were found in a wide area of the brain. The wide spectrum of initial target cells following MK-p10 infection, as well as its faster spread in the brain, may be evidence of enhanced virulence in suckling mice.


2020 ◽  
Vol 6 (3) ◽  
Author(s):  
Leila Arab ◽  
Aslan Fanni ◽  
Shiva Nemati ◽  
Ehsan Arefian ◽  
Jafar Ai ◽  
...  

Objective: In this study, we evaluated the effects of human embryonic derived neural progenitor cells on neurological score, histopathological changes, and miRNA-210 as biomarkers of regeneration. Methods: The animals were randomly divided into the four groups: Sh (sham), MCAO (middle cerebral artery occlusion), MCAO+PBS, MCAO+Cell. One day after MCAO induction, embryonic derived neural progenitor cells (hESC-NPCsGFP) or PBS were injected intracerebroventriculary in MCAO+Cell or MCAO+PBS groups. On day 1, 2, 3, and 7 after ischemia induction, the neurological score was tested in each rat. At 48h, the expression of miRNA-210 was evaluated and 7 days after, the pathological assessments were performed by H&E staining. Results: Neurological score showed the promotion of functional recovery in MCAO+Cell group. Based on H&E staining, the percentage of neural death in ischemic region reduced in MCAO+Cell group. The miRNA-210 significantly upregulated in both brain and blood samples. Conclusion: According to the findings, hESC-NPCsGFP injection could up-regulate the miRNA-210 of tissue and blood to support the neuroprotective and regenerative effect of hESC-NPCsGFP in the ischemic lesion and improved the neurological score and reduce the neural death in ischemic region.


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