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  • Ovid Technologies (Wolters Kluwer Health)  (59)
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  • 1
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2015
    In:  Chinese Medical Journal Vol. 128, No. 3 ( 2015-02-05), p. 425-426
    In: Chinese Medical Journal, Ovid Technologies (Wolters Kluwer Health), Vol. 128, No. 3 ( 2015-02-05), p. 425-426
    Type of Medium: Online Resource
    ISSN: 0366-6999
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2015
    detail.hit.zdb_id: 2108782-9
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  • 2
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 42, No. 2 ( 2011-02), p. 459-464
    Abstract: Bone marrow stromal cells (BMSC) decrease neurological deficits in rodents after stroke and concomitantly induce extensive neurite remodeling in the brain, which highly correlates with the improvement of neurological function. We investigated the effects of endogenous tissue plasminogen activator (tPA) on neurite remodeling after BMSC treatment. Methods— Adult C57BL/6 wild-type (WT) mice and tPA knockout (tPA −/− ) mice were subjected to middle cerebral artery occlusion, followed by an injection of 1×10 6 BMSC (n=18) or phosphate-buffered saline (n=18) into the tail vein 24 hours later. Behavioral tests were performed at 3, 7, and 14 days after middle cerebral artery occlusion. Animals were euthanized at 14 days after stroke. Results— The effects of BMSC on functional recovery depended on presence or absence of tPA, even after adjusting for imbalanced stroke severity. BMSC significantly improve functional recovery in WT mice compared to WT controls but show no beneficial effect in the tPA −/− mice compared to tPA −/− controls. Axonal density and synaptophysin-positive areas along the ischemic boundary zone of the cortex and striatum in WT mice are significantly higher than in the tPA −/− mice. BMSC treatment significantly increases tPA protein level and activity only in WT mice. Conclusions— Our results suggest that endogenous tPA promotes BMSC-induced neurite outgrowth and may contribute to functional recovery after stroke.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2011
    detail.hit.zdb_id: 1467823-8
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  • 3
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Chinese Medical Journal Vol. 134, No. 14 ( 2021-07-20), p. 1639-1654
    In: Chinese Medical Journal, Ovid Technologies (Wolters Kluwer Health), Vol. 134, No. 14 ( 2021-07-20), p. 1639-1654
    Type of Medium: Online Resource
    ISSN: 0366-6999 , 2542-5641
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2108782-9
    SSG: 6,25
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  • 4
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 112, No. 22 ( 2005-11-29), p. 3486-3494
    Abstract: Background— Microvascular dysfunction posttreatment of stroke with recombinant human tissue-type plasminogen activator (rht-PA) constrains the therapeutic window to 3 hours. Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) promote vascular thrombolysis and reduce the inflammation response. We therefore investigated the neuroprotective effects of a combination of atorvastatin and delayed rht-PA treatment in a rat model of embolic stroke. Methods and Results— Rats subjected to embolic middle cerebral artery occlusion were treated with atorvastatin in combination with rht-PA 4 hours after stroke. Magnetic resonance imaging measurements revealed that combination treatment with atorvastatin and rht-PA blocked the expansion of the ischemic lesion, which improved neurological function compared with saline-treated rats. Real-time reverse transcription–polymerase chain reaction analysis of single endothelial cells isolated by laser-capture microdissection from brain tissue and immunostaining showed that combination treatment downregulated expression of tissue factor, von Willebrand factor, protease-activated receptor-1, intercellular adhesion molecule-1, and matrix metalloproteinase-9, which concomitantly reduced cerebral microvascular thrombosis and enhanced microvascular integrity. Combination treatment did not increase cerebrovascular endothelial nitric oxide synthase (eNOS) levels or eNOS activity, and inhibition of NOS activity with N -nitro- l -arginine methyl ester did not block the beneficial effects of combination treatment on stroke. Furthermore, combination treatment compared with thrombolytic monotherapy increased cerebral blood flow and reduced infarct volume in eNOS-null mice. Conclusions— These data demonstrate that combination treatment with atorvastatin and rht-PA exerts a neuroprotective effect when administered 4 hours after stroke and that the therapeutic benefits are likely attributed to its multitargeted effects on cerebrovascular patency and integrity.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2005
    detail.hit.zdb_id: 1466401-X
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  • 5
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2007
    In:  Chinese Medical Journal Vol. 120, No. 22 ( 2007-11), p. 2056-2058
    In: Chinese Medical Journal, Ovid Technologies (Wolters Kluwer Health), Vol. 120, No. 22 ( 2007-11), p. 2056-2058
    Type of Medium: Online Resource
    ISSN: 0366-6999
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2007
    detail.hit.zdb_id: 2108782-9
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  • 6
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Chinese Medical Journal Vol. 130, No. 14 ( 2017-07-20), p. 1694-1699
    In: Chinese Medical Journal, Ovid Technologies (Wolters Kluwer Health), Vol. 130, No. 14 ( 2017-07-20), p. 1694-1699
    Type of Medium: Online Resource
    ISSN: 0366-6999
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 2108782-9
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  • 7
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 43, No. suppl_1 ( 2012-02)
    Abstract: Background: The Sonic hedgehog (Shh) pathway regulates stroke-induced neurogenesis. The present study investigated the functional role of the microRNA 17-92 (miR17-92) cluster in this process. Methods and Results: Analysis of miRNA microarray and real-time RT-PCR revealed that stroke substantially increased levels of individual members of the miR17-92 cluster: miR-18a (1.8±0.3), miR-19a (2.5±0.4), and miR-92a (1.9±0.3) expression in neural progenitor cells (NPCs) harvested from the subventricular zone (SVZ) of ischemic rats (n=6). Overexpression of the miR17-92 cluster in cultured NPCs significantly increased NPC proliferation measured by the number of BrdU positive cells (52±4% vs 28±2% in empty vector, n=3/group, p 〈 0.05). Concurrently, overexpression of the miR17-92 cluster reduced PTEN (phosphatase and tensin homolog), a target of the miR17-92 cluster, protein levels by 70% compared to levels in NPCs transfected with an empty vector. PTEN suppresses cell proliferation. These data suggest that the stroke-upregulated miR17-92 cluster enhances NPC proliferation via downregulation of PTEN. To examine whether Shh regulates miR17-92 cluster expression, NPCs were incubated with recombinant human Shh (rhShh, 100ng/ml). We found that rhShh significantly (p 〈 0.05) increased levels of individual members of the miR17-92 cluster: miR-18a (2.1±0.1), miR-19a (1.3±0.7), miR-19b (1.5±0.6) and miR-92a (1.9±0.8). Blockage of a Shh receptor Smo with cyclopamine suppressed rhShh-increased levels of miR-18a (0.9±0.08), miR-19a (0.7±0.01), miR-19b (0.6±0.05) and miR-92a (0.8±0.04). Attenuation of endogenous Shh in NPCs with siRNA also substantially decreased levels of miR-18a (0.6±0.1), miR-19a (0.4±0.05) and miR-92a (0.6±0.1) compared with levels in NPCs transfected with scrambled siRNA (1.0±0.2, n=3), indicating that Shh regulates miR17-92 expression. MYC is a downstream target of Shh. Western blots showed that stroke increased the protein level of N-MYC 1.8 fold in SVZ tissues and incubation of NPCs with rhShh elevated N-MYC levels by 1.8 fold, which was abrogated by cyclopamine (1.3 fold). N-MYC transduction resulted in significant increases in expression of the primary miR17-92 cluster (2.1±0.3 vs 1.0±0.2 in control group, n=3, p 〈 0.05). These data suggest that the Shh pathway recruits N-MYC to regulate miR17-92 cluster expression in NPCs. Conclusion: Our data suggest a functional role of the miR17-92 cluster in mediating stroke-induced neurogenesis by the SHH/MYC signaling pathway, which provides new insight into molecular mechanisms of stroke-induced neurogenesis.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2012
    detail.hit.zdb_id: 1467823-8
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  • 8
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 35, No. 12 ( 2004-12), p. 2890-2895
    Abstract: Background and Purpose— Occlusion of the middle cerebral artery triggers platelet accumulation at the site of occlusion and in downstream microvessels. The platelet-induced secondary thrombosis promotes the progressive development of ischemic brain damage and contributes to the resistance to thrombolysis and to the tight 3-hour therapeutic window. We tested the hypothesis that combination of intravenous (IV) administration of a GPIIb/IIIa receptor antagonist, 7E3 F(ab′) 2 , with intra-arterial (IA) administration of tenecteplase–tissue plasminogen activator (TNK-tPA) increases the efficacy of thrombolysis and extends the therapeutic window of stroke. Methods— Rats subjected to embolic stroke were treated with IV 7E3 F(ab′) 2 (6 mg/kg) in combination with IA or IV TNK-tPA (5 mg/kg) at 4 and 6 hours after onset of stroke, respectively; IA TNK-tPA (5 mg/kg) alone at 6 hours after onset of stroke; or saline at 6 hours after onset of stroke. Results— The combination of IV 7E3 F(ab′) 2 (4 hours) and IA TNK-tPA (6 hours) significantly ( P 〈 0.05) reduced infarct volume and improved neurological functional deficits, which was associated with significant ( P 〈 0.05) reductions in the size of embolus at the origin of the occluded middle cerebral artery and in down-stream microvascular platelet and fibrin deposition, and enhanced microvascular patency compared with saline-treated rats. However, combination of IV 7E3 F(ab′) 2 (4 hours) and IV TNK-tPA (6 hours) or IA TNK-tPA (6 hours) alone failed to reduce infarct volume and improve neurological function compared with the saline-treated rats. No significant differences of the incidence of hemorrhage were detected among groups. Conclusions— These data suggest that the combination of IV 7E3 F(ab′) 2 (4 hours) and IA TNK-tPA (6 hours) extends the therapeutic window of thrombolysis to 6 hours after stroke.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2004
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  • 9
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 52, No. Suppl_1 ( 2021-03)
    Abstract: Background: Adult neurogenesis facilitates brain remodeling after stroke. Exosomes derived from neural stem cells (NSCs) promote ischemic neurovascular remodeling including angiogenesis and axonal outgrowth, potentially by transferring their cargo proteins and miRNAs to recipient cells. However, cargo profiles of proteins and miRNAs in NSC exosomes have not been investigated. Methods: Exosomes were isolated from supernatants of cultured NSCs harvested from the subventricular zone of rats subjected to 7 day middle cerebral artery occlusion (MCAO) and non-MCAO rats, respectively. Mass spectrometry and miRNA array were utilized to determine the protein and miRNA profiles of NSC-derived exosomes (NSC-Exos). Bioinformatic pathway analyses were performed using Ingenuity Pathway Analysis (IPA). Results: Exosome markers and size distribution (50-200nm) were validated with Western blot, transmission electron microscopy and Nanosight measurements, respectively. Proteomics analysis yielded a total of 1,770 proteins in ischemic NSC-Exos. Bioinformatics analysis identified 24, 23 and 23 proteins that were related to neuronal cell proliferation, migration and differentiation, respectively. Intriguingly, enrichment signaling pathway analysis revealed cargo proteins in ischemic NSC-Exos were highly associated with dysfunction, membrane, and permeability of mitochondrion, indicating a critical role of extracellular mitochondrion in stroke-induced neurogenesis. In addition, 318 miRNAs were detected in ischemic NSC-Exos. Gene ontology analysis demonstrated that differentially expressed miRNAs between ischemic and non-ischemic NSC-Exos were highly related to inflammation, cell proliferation, cell cycle, and differentiation. The top 3 upregulated miRNAs including miR-106b, miR-542,miR-125b were validated in ischemic NSC-Exos using RT-PCR. The functions of these miRNAs are related to the induction of angiogenesis. Summary/Conclusion: Our results for the first time demonstrate that ischemic NSC-Exos contain a robust profile of protein and miRNA effectors, which may provide new insights into the function of NSC-Exos in stroke-induced neurogenesis and potentially lead to new therapeutic targets against stroke.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1467823-8
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  • 10
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 44, No. suppl_1 ( 2013-02)
    Abstract: Stroke induces angiogenesis in the peri-infarct region. It is not known whether angiogenesis occurs in the subventricular zone (SVZ) of the lateral ventricle after stroke. The SVZ is a neural stem cell niche containing vascular plexus that supports adult neurogenesis. We characterized longitudinal changes of vascular structures in the SVZ niche after stroke using whole mounts, an organotypic preparation of the SVZ in which the 3D cell-vessel relationships are preserved. Adult mice were subjected to middle cerebral artery occlusion (MCAO). The vascular architectures within the 50 μm thick SVZ of immunostained whole mounts were imaged by 3D confocal microscopy. In non-MCAO mice (n=4), 2±0.2% of endothelial cells were proliferative (BrdU+/CD31+). Blood vessels in this niche constituted 2.6±0.01% of the total volume with 75±17 vascular branches. However, 7 and 14 days after MCAO, proliferated endothelial cells significantly (p 〈 0.05) increased to 12±1% (n=5) and 15±1 % (n=5), respectively, which was followed by substantial increases in vascular volume at 14 (4.2±0.01%, n=3), 30 (4.9±0.05%, n=3), and 90 (5.7±0.01%, n=3) days, but not at 7 days after MCAO. Moreover, vascular branches increased significantly to 156±27 and 216±8 at 30 and 90 days, respectively, but not at 14 days. Interestingly, we detected increases in the number of string-like vessels starting at 14 days (731±79/mm 3 vs 476±41/mm 3 in control) which increased and persisted at 30 (1,824±255/mm 3 ) and 90 (1,748±204/mm 3 ) days after MCAO. These string-like vessels were not perfused by plasma. String vessels increase during embryonic angiogenesis. Collectively, these data indicate that stroke induces angiogenesis in the SVZ, which lasts at least 90 days after stroke. Moreover, stroke significantly increased neural stem cells (BrdU + /GFAP + , 13±3%, 15±3%, and 11±4% at 7, 14, and 90 days, respectively, vs 6±1% in control) and newborn neurons (BrdU + /DCX + , 14±2% and 12±2.0% at 7 and 14 days, respectively, vs 4±1% in control). Neural stem cells at the ventricular surface extended their processes to the blood vessels in the SVZ. Our data indicate that stroke induces angiogenesis in the SVZ, which is associated with stroke-induced neurogenesis.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2013
    detail.hit.zdb_id: 1467823-8
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