scholarly journals Human embryonic derived neural progenitor cells improves neurological scores following brain ischemia/ reperfusion: Modulation of blood and brain tissue MicroRNA-210

2020 ◽  
Vol 6 (3) ◽  
Author(s):  
Leila Arab ◽  
Aslan Fanni ◽  
Shiva Nemati ◽  
Ehsan Arefian ◽  
Jafar Ai ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Ischemia Reperfusion ◽  
Neural Progenitor ◽  
Artery Occlusion ◽  
Cell Group ◽  
Ischemic Lesion ◽  
Ischemic Region ◽  
Neurological Score ◽  
Cerebral Artery Occlusion

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.

scholarly journals Effects of Administration Route on Migration and Distribution of Neural Progenitor Cells Transplanted into Rats with Focal Cerebral Ischemia, an MRI Study

2009 ◽  
Vol 30 (3) ◽  
pp. 653-662 ◽  
Author(s):  
Lian Li ◽  
Quan Jiang ◽  
Guangliang Ding ◽  
Li Zhang ◽  
Zheng Gang Zhang ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Focal Cerebral Ischemia ◽  
Three Dimensional ◽  
Neural Progenitor ◽  
Artery Occlusion ◽  
Blue Staining ◽  
Ischemic Lesion ◽  
Administration Routes ◽  
Male Wistar Rats

We tested the hypotheses that administration routes affect the migration and distribution of grafted neural progenitor cells (NPCs) in the ischemic brain and that the ischemic lesion plays a role in mediating the grafting process. Male Wistar rats ( n=41) were subjected to 2-h middle cerebral artery occlusion (MCAo), followed 1 day later by administration of magnetically labeled NPCs. Rats with MCAo were assigned to one of three treatment groups targeted for cell transplantation intra-arterially (IA), intracisternally (IC), or intravenously (IV). MRI measurements consisting of T2-weighted imaging and three-dimensional (3D) gradient echo imaging were performed 24 h after MCAo, 4 h after cell injection, and once a day for 4 days. Prussian blue staining was used to identify the labeled cells, 3D MRI to detect cell migration and distribution, and T2 map to assess lesion volumes. Intra-arterial (IA) administration showed significantly increased migration, a far more diffuse distribution pattern, and a larger number of transplanted NPCs in the target brain than IC or IV administration. However, high mortality with IA delivery (IA: 41%; IC: 17%; IV: 8%) poses a serious concern for using this route of administration. Animals with smaller lesions at the time of transplantation have fewer grafted cells in the parenchyma.

Abstract 2976: Sildenafil Enhances Neurogenesis And Oligodendrogenesis In The Ischemic Brain Of Aged Mouse

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Rui Lan Zhang ◽  
Michael Chopp ◽  
Cynthia Roberts ◽  
Min Wei ◽  
Xinli Wang ◽  
...  
Keyword(s):  
Corpus Callosum ◽  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Pde5 Inhibitor ◽  
Neural Progenitor ◽  
Artery Occlusion ◽  
Immunofluorescent Staining ◽  
Aged Mouse ◽  
Ischemic Brain ◽  
Physics Department

Sildenafil enhances neurogenesis and oligodendrogenesis in the ischemic brain of aged mouse Rui Lan Zhang 1 , Michael Chopp 1,2 Cynthia Roberts 1 , Min Wei 1 , Xinli Wang 1 , Xianshuang Liu 1 , Zheng Gang Zhang 1 Departments of 1 Neurology and Henry Ford Hospital, Detroit, MI, USA 2 Oakland University, Physics Department, Rochester, MI, USA. Background and Purpose: Nestin lineage neural progenitor cells contribute to neurogenesis in adult rodent brain under non-ischemic and ischemic conditions. The present study investigated the effect of sildenafil, a potent phosphodiesterase 5 (PDE5) inhibitor, on nestin lineage neural progenitor cells in the aged mouse after stroke. Methods: Male Nestin-CreER T2 ;R26R-stop-YFP mice at age 16 months were used. Tamoxifen was daily injected for 5 days to activate Cre/loxP system under control of the nestin promoter, leading to permanent YFP labeling of nestin lineage cells. These mice were subjected to permanent middle cerebral artery occlusion (MCAo) 14 days after the last tamoxifen injection. Sildenafil at 10mg/kg (n=11) or saline (n=10) was aadministered daily for 7 days starting 1 day after MCAo. All mice were sacrificed 30 days after MCAo. The number of nestin lineage cells and their fate were analyzed using immunohistochemistry staining. Results: Double immunofluorescent staining confirmed YFP positive cells were nestin positive. Unbiased stereological analysis revealed that sildenafil treatment significantly increased (p<0.05) the number of nestin linage cells in the ischemic subventricular zone (SVZ, 803 ± 28 vs 657 ± 41 in saline), striatum (3739 ± 162 vs 3029 ± 144 in saline), and corpus callosum (2957 ± 86 vs 2578 ± 117 in saline). Phenotype analysis showed that sildenafil substantially augmented the number of nestin lineage neuroblasts identified by doublecortin positive cells (19.4 ± 1.6 % vs 12.9 ± 1.1 % in saline), nestin lineage mature neurons measured by NeuN (6.2 ± 0.8 % vs 3.0 ± 0.6 %) and calbindin (10.8 ± 0.9 vs 7.2 ± 1.1) positive cells in the ischemic striatum. Sildenafil also significantly (p<0.05) increased the number of nestin lineage oligodendrocytes measured by 2’, 3’-cyclic nucleotide, 3’-phosphodiesterase (CNPase) positive cells in ischemic striatum (21.3 ± 1.2 vs 19.9 ± 1.4 in saline) and corpus callosum (18.9 ± 1.4 vs 14.4 ± 1.3 in saline). Conclusion: Our data demonstrate that sildenafil enhances neurogenesis and oligodendrogenesis in the ischemic brain of the aged mouse, which could contribute sildenafil-improved neurological outcome after stroke which we have demonstrated.

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 ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Ischemia Reperfusion ◽  
Brain Slices ◽  
Neural Progenitor ◽  
Short Term ◽  
Hippocampal Ca1 ◽  
Ca1 Area ◽  
Adaptation Processes ◽  
The Brain

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.

Abstract 141: The Microrna 17-92 Cluster in Neural Progenitor Cells is Required for Stroke-induced Neurogenesis and Gliogenesis

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Wanlong Pan ◽  
Xianshuang Liu ◽  
Xiaoming Zhang ◽  
Xinli Wang ◽  
Jiani Hu ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Molecular Mechanisms ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Artery Occlusion ◽  
Tamoxifen Treatment ◽  
Oligodendrocyte Progenitor Cells ◽  
Factor Inhibitor

Background: Molecular mechanisms underlying stroke-induced neurogenesis have not been fully investigated. The microRNA 17-92 cluster (miR17-92) regulates proliferation and differentiation of adult neural progenitor cells (NPCs). The present study investigated whether the miR17-92 cluster in NPCs is required for stroke-induced neurogenesis. Methods and Results: Mice with inducible and conditional knockdown of the miR17-92 cluster in nestin lineage NPCs (nestin-CreER T2 /miR17-92 -/- , 17-92-cKO, n=9) and wild-type litters (WT, n=9) were treated by tamoxifen. Administration of tamoxifen resulted in more than 60% reduction of individual members of the miR-17-92 cluster (miR-17: 1.0 vs 0.4; miR-19a: 1.0 vs 0.3; miR-19b: 1.0 vs 0.2; miR-20a: 1.0 vs 0.4; miR-92a: 1.0 vs 0.4 fold in WT, p<0.05) in NPCs localized to the subventricular zone (SVZ). Two days after termination of tamoxifen treatment, these mice were subjected to permanent right middle cerebral artery occlusion (MCAO) and sacrificed 28 days post-MCAo. Compared to WT mice, 17-92-cKO mice exhibited significant (p<0.05) reduction of proliferation of NPCs measured by the number of Ki67 + cells (226±43 vs 471±100 cells/mm 2 ) and the number of DCX + neuroblasts (11±2% vs 24±4% ) in the ischemic SVZ. Cultured NPCs harvested from ischemic cKO mice showed significant (p<0.05) reduction of BrdU + cells (37±2% vs 61±4% WT , n=3/group), Tuj1 + neuroblasts (5±0.2% vs 9±0.4% ), GFAP + cells (33±3% vs 53±2% ), and NG2 + oligodendrocyte progenitor cells (OPCs, 3±0.1% vs 5±0.5%). These in vivo and in vitro data indicate that reduction of the miR17-92 cluster suppresses stroke-induced neurogenesis and gliogenesis. Western blot analysis showed that miR17-92 cKO significantly (p<0.05) increased and reduced a cytoskeleton-associated protein, Enigma homolog1 (ENH1, 1.6 vs 1.0 fold), and its down-stream transcription factor, inhibitor of differentiation1 (ID1, 1.0 vs 0.6 fold), respectively. ENH1 is a putative target of the miR17-92 cluster. Conclusion: Our data indicate that the miR17-92 cluster in adult nestin lineage NPCs is required for stroke-induced neurongenesis and gliogenesis, and that the miR17-92 cluster possibly targets ENH1/ID1 signaling.

scholarly journals Therapeutic Effects in a Transient Middle Cerebral Artery Occlusion Rat Model by Nose-To-Brain Delivery of Anti-TNF-Alpha siRNA with Cell-Penetrating Peptide-Modified Polymer Micelles

Pharmaceutics ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 478 ◽  
Author(s):  
Takanori Kanazawa ◽  
Takumi Kurano ◽  
Hisako Ibaraki ◽  
Yuuki Takashima ◽  
Toyofumi Suzuki ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Therapeutic Effects ◽  
Brain Delivery ◽  
Infarcted Area ◽  
Neurological Score ◽  
Tnf Α ◽  
Cerebral Ischemia Reperfusion Injury ◽  
Cerebral Artery Occlusion

We previously reported that siRNA delivery to the brain is improved by the nose-to-brain delivery route and by conjugation with polyethylene glycol-polycaprolactone (PEG-PCL) polymer micelles and the cell-penetrating peptide, Tat (PEG-PCL-Tat). In this study, we evaluated the nose-to-brain delivery of siRNA targeting TNF-α (siTNF-α) conjugated with PEG-PCL-Tat to investigate its therapeutic effects on a transient middle cerebral artery occlusion (t-MCAO) rat model of cerebral ischemia-reperfusion injury. Intranasal treatment was provided 30 min after infarction induced via suturing. Two hours after infarction induction, the suture was removed, and blood flow was released. At 22 h post-reperfusion, we assessed the infarcted area, TNF-α production, and neurological score to determine the therapeutic effects. The infarcted area was observed over a wide range in the untreated group, whereas shrinkage of the infarcted area was observed in rats subjected to intranasal administration of siTNF-α with PEG-PCL-Tat micelles. Moreover, TNF-α production and neurological score in rats treated by intranasal administration of siTNF-α with PEG-PCL-Tat micelles were significantly lower than those in untreated and naked siTNF-α-treated rats. These results indicate that nose-to-brain delivery of siTNF-α conjugated with PEG-PCL-Tat micelles alleviated the symptoms of cerebral ischemia-reperfusion injury.

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